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BACKGROUND AND AIMS we know little about clinical outcomes of arterial calcifications. This study investigates the risk factors of intracranial artery calcifications and its association with cardiovascular disease and cognitive function. METHODS patients were recruited from a Dutch memory clinic, between April 2009 and April 2015. The intracranial internal carotid artery (iICA) and basilar artery were analysed on the presence of calcifications. Calcifications in the iICA were also assessed on severity and location in the tunica intima or tunica media. Using logistic regression, risk factors of intracranial artery calcifications were analysed, as well as the association of these calcifications with cardiovascular disease, cognitive function and type of cognitive disorder (including subjective cognitive impairment, mild cognitive impairment and dementia). Cognitive function was assessed with the Cambridge Cognitive Examination. RESULTS 1992 patients were included (median age: 78.2 years, ±40% male). The majority of patients had calcifications in the iICA (±95%). Basilar artery calcifications were less prevalent (±8%). Risk factors for cerebral intracranial calcifications were age (p

Over 200 million individuals worldwide are estimated to have peripheral artery disease (PAD). Although the term peripheral can refer to any outer branch of the vasculature, the focus of this review is on lower-extremity arteries. The initial sequelae of PAD often include movement-induced cramping pain in the hips and legs or loss of hair and thinning of the skin on the lower limbs. PAD progresses, sometimes rapidly, to cause nonhealing ulcers and critical limb ischemia which adversely affects mobility and muscle tone; acute limb ischemia is a medical emergency. PAD causes great pain and a high risk of amputation and ultimately puts patients at significant risk for major adverse cardiovascular events. The negative impact on patients’ quality of life, as well as the medical costs incurred, are huge. Atherosclerotic plaques are one cause of PAD; however, emerging clinical data now shows that nonatherosclerotic medial arterial calcification (MAC) is an equal and distinct contributor. This ATVB In Focus article will present the recent clinical findings on the prevalence and impact of MAC in PAD, discuss the known pathways that contribute specifically to MAC in the lower extremity, and highlight gaps in knowledge and tools that limit our understanding of MAC pathogenesis.

IntroductionThe atrial muscle sleeve (AMS) of the pulmonary vein is the most common source of the arrhythmogenic triggers in atrial fibrillation (AF). Anatomical substrate generating these ectopic currents is still elusive. The present study was designed to study the AMS of pulmonary veins with an emphasis on the structural basis which might govern AF initiation and perpetuation.Materials and MethodsThe study was conducted on longitudinal tissue section of pulmonary vein, taken from 15 human cadaveric non-diseased hearts. Tissue was studied histologically using H&E and Gömöri trichrome stain. The pacemaker channels were identified by immunohistochemistry using monoclonal HCN4 and HCN1 antibodies.ResultsThe AMS was identified in each pulmonary vein, located between the tunica adventitia and tunica media. A node like arrangement of myocytes was seen within the AMS in 30% of veins. It had a compact zone limited by a fibrous capsule and contained much smaller, paler and interconnected myocytes. Outside the capsule there was a zone of dispersed, singly placed myocytes separating the compact zone from the working myocytes of the AMS. HCN4 and HCN1 antibodies were expressed on the cell membrane of nodal myocytes, while the working myocytes demonstrated none to minimal staining.ConclusionPulmonary veins nodes are similar to the specialized cardiac conductive tissue in, histological arrangement of compact and transitional zones, cellular characteristics, and the presence of pacemaker channels. They might be the anatomical basis of ectopic arrhythmogenic foci. To our knowledge these nodes are being described for the first time in human.

Patients with congenital adrenal hyperplasia (CAH) are at increased risk of cardiometabolic abnormalities. We aimed to evaluate vascular endothelial dysfunction and its association with serum neopterin (NP) levels in CAH patients.The study included 40 patients, with a mean age of 14.8 ± 2.6 years; 28 (70%) subjects were females. They were compared with 40 healthy controls matched in anthropometric evaluation and measurement of fasting lipids, glucose, insulin, homeostasis model assessment for insulin resistance [HOMA-IR], and serum NP levels (nmol/L). Vascular ultrasound was used to measure brachial artery flow-mediated dilation (FMD%) and carotid intima-media thickness (CA-IMT). According to the degree of control on medical treatment, patients were classified into poor (n = 12) and good (n = 28) control groups.Compared to controls, CAH patients had lower brachial FMD% (4.60 ± 2.13 versus 9.31 ± 2.29, p = 0.001), similar CA-IMT (0.44 ± 0.08 versus 0.44 ± 0.06, p = nonsignificant) and higher NP (42.6 ± 11.6 versus 9.2 ± 3.8, p = 0.001). However, differences between poor and good control CAH patients were significant regarding FMD%, CA-IMT, and NP measurements. FMD% correlated significantly with NP (r = -0.54, p = 0.001), high-sensitivity CRP (r = -0.53, p = 0.001), HOMA-IR (r = -0.31, p = 0.01), CA-IMT (r = -0.22, p 0.05), diastolic blood pressure (r = 0.32, p = 0.01) and systolic blood pressure (r = -0.022, p 0.05). NP was the most significant independent predictor of FMD%, as determined by linear regression analysis (p = 0.001).Our study showed that CAH patients had endothelial dysfunction, which is an early process of vascular affection. This was significantly associated with NP levels, suggesting a crucial role of inflammation in the pathogenesis of vascular damage. Further studies are needed to confirm our findings and to investigate the exact role of NP, as either protective or proatherothrombotic.

AIM The aim of this study was to detect macrovascular findings in systemic sclerosis (SSc) by means of color Doppler ultrasonography (CDUS) and to evaluate the relationship between the laboratory and clinical findings in the setting of the disease. METHODS This was a cross-sectional study. Eighty-eight patients were included in the study. CDUS examinations of the bilateral carotid, vertebral, and peripheral arteries were performed. The presence of macrovascular involvement was investigated and recorded, and its relationships with the clinical, laboratory, and cardiovascular risk factors were evaluated. RESULTS An atheromatous plaque was found in 67.7% of the 1936 arteries examined by CDUS. Of these 1936 arteries, 37.4% demonstrated a narrowing of the intraluminal diameter. On the other hand, the carotid intima-media thickness (CIMT) was found to have increased in 55.7% of the patients. This increase was found to be statistically correlated with disease duration, the modified Rodnan Skin Thickness Score, and the Medsger Disease Activity Score. But no relation existed with the disease subtype, age, or cardiovascular risk factors. Arterial occlusion was detected in 10 patients. An association was found between the CIMT values and arterial occlusion. CONCLUSIONS In this study, we examined the arteries by means of CDUS, and we detected structural alterations in the peripheral and carotid arteries. We witnessed that these macrovascular changes had a close association with certain features of SSc. We think there is a need for broader prospective studies in order to evaluate the contribution of these factors to the macrovascular changes stated in the article.

Arterial calcification is an important risk factor for patients with end-stage renal disease. Despite substantial research efforts, the detailed mechanisms of the process of arterial calcification in end-stage renal disease remain unclear. miR-133a expression in radial artery samples was detected by FISH and Alizarin Red Staining. The expressions of miR-133a and RUNX2 in A7r5 cells with BMP2 induction were detected by qRT-PCR. In addition, qRT-PCR, Western blot, and ELISA assay were performed to detect changes in miR-133a levels in A7R5 cells after different treatments. Alizarin Red staining showed that red crystal deposition occurred in the tunica media. FISH analysis indicated that miR-133a was upregulated in the tunica media of the radial artery samples without calcification when compared with those with calcification. We also found that expression of RUNX2 in A7r5 cells increased at day 7 and day 14 after BMP2 induction and decreased miR-133a expression decreased at day 14. In addition, RUNX2 protein and OCN expression were upregulated in A7r5 cells during BMP2-induced calcification. When miR-133a expression was suppressed, cell calcification aggravated, which led to upregulation of RUNX2 and OCN. When miR-133a was overexpressed, calcification of cells was inhibited, resulting in downregulation of RUNX2 and OCN. The present study reveals that miR-133a could indirectly regulate cell calcification through the RUNX2 gene expression. Our findings provide insight into the potential use of miR-133a as a molecular target for diagnosing vascular calcification in end-stage renal disease.

Long-term in vivo observation in large animal model is critical for evaluating the potential of small diameter tissue engineering vascular graft (SDTEVG) in clinical application, but is rarely reported. In this study, a SDTEVG is fabricated by the electrospinning of poly(ε-caprolactone) and subsequent heparin modification. SDTEVG is implanted into canine's abdominal aorta for 511 days in order to investigate its clinical feasibility. An active and robust remodeling process was characterized by a confluent endothelium, macrophage infiltrate, extracellular matrix deposition and remodeling on the explanted graft. The immunohistochemical and immunofluorescence analysis further exhibit the regeneration of endothelium and smooth muscle layer on tunica intima and tunica media, respectively. Thus, long-term follow-up reveals viable neovessel formation beyond graft degradation. Furthermore, the von Kossa staining exhibits no occurrence of calcification. However, although no TEVG failure or rupture happens during the follow-up, the aneurysm is found by both Doppler ultrasonic and gross observation. Consequently, as-prepared TEVG shows promising potential in vascular tissue engineering if it can be appropriately strengthened to prevent the occurrence of aneurysm.

A 45-year-old woman with no known medical history died suddenly shortly after complaining of anterior chest discomfort. The autopsy revealed a dissection at the anterior descending branch of the left coronary artery, and eosinophilic adventitial inflammation was observed both in the right coronary artery and in the vicinity of the dissection. Furthermore, there was degeneration of the tunica media in the right coronary artery, and this was thought to be a predissection lesion. In the degenerated area of the tunica media, probable apoptosis of smooth muscle cells was noted, suggesting that the degeneration was not due only to the effect of eosinophilic lytic enzymes. These findings also indicated that eosinophilic infiltration preceded the dissection. Eosinophilic infiltration around the coronary arteries is occasionally observed in cases of sudden death, but although it might be associated with the death, the pathological mechanism is yet to be elucidated. Eosinophilic periarteritis has also been observed around the site of spontaneous coronary artery dissection, although a causal relationship is unproven. The histopathology of this case indicated that the eosinophilic infiltration preceded the dissection. Detailed pathological findings are presented, together with a review of the literature.

Összefoglaló. A vena cava inferior leiomyosarcomája a vena tunica mediájából kiinduló igen ritka rosszindulatú daganat. Tünetei és radiomorfológiai jelei nem mindig juttatnak pontos kórisméhez, szövettani mintavétele pedig elhelyezkedése miatt veszélyes lehet. Diagnózisa ezért sokszor jelent kihívást a klinikusok számára. Kezelése elsősorban sebészi, amelyet együtt vagy monoterápiában alkalmazott radioterápia és kemoterápia egészít ki. Esetünkben egy 74 éves nőbeteg tünetmentes, a v. cava inferior jobb v. renalis fölötti részének jobb mellékvesével összefüggő tumorát találtuk. Endokrinológiai kivizsgálása során a szérum kortizol, adrenalin, noradrenalin, adenocorticotrop hormon (ACTH), teljes és szabad tesztoszteron, dehidroepiandroszteron-szulfát (DHEA-S), nemi hormon kötőfehérje (sex hormone binding globulin, SHBG) normál tartományban volt, a tumor hormonszekréciót nem mutatott. A tumor sebészi eltávolítása mellett döntöttünk. Preoperatív biopsziát annak kockázatai miatt nem végeztünk. A műtét során a v. cava inferior daganatát találtuk, a tumor eltávolítását végeztük a vena falának resectiójával, a jobb mellékvese eltávolításával és a jobb v. renalis neoimplantatiójával. A jobb feltárás érdekében a műtét elején cholecystectómiát is végeztünk. A műtét után szövődmény nem jelentkezett. A beteg adjuváns radioterápiában részesült. A tumor korai diagnózisának és en bloc resectiójának köszönhetően jelentősen növeltük a beteg gyógyulási esélyeit, az elvégzett radioterápiával pedig csökkentettük a recidíva valószínűségét. Summary. Leiomyosacroma of the inferior vena cava is an extremely rare malignancy originating from the tunica media of the venous wall. Its symptoms and radiomorphological signs do not always lead to an accurate diagnosis. Histological sampling can be dangerous due to its location. Therefore the diagnosis is often a challenge for clinicians. Its treatment is primarily surgical, supplemented by radiotherapy and chemotherapy applied together or in monotherapy. In our case, an asymptomatic 74-year-old female patient was diagnosed with a tumor of the inferior caval vein located just above the right renal vein and involving the right adrenal gland. As serum cortisol, epinephrine, norepinephrine, adrenocorticotropic hormone (ACTH), total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding globulin (SHBG) was at normal level, the tumor showed no hormone secretion. Primary surgical resection was planned. Preoperative biopsy was not performed due to its high risk of complications. During operation, tumor resection was performed by resection of the venous wall, removal of the right adrenal gland and neoimplantation of the right renal vein. For better exposure, cholecystectomy was also performed at the beginning of surgery. There were no postoperative complications. The patient received adjuvant radiation therapy. Thanks to the early diagnosis of the tumor and the complete resection, we significantly increased the patient’s chances of total recovery. With the radiotherapy performed, we reduced the likelihood of tumor recurrence.

Accurately identifying coronary artery disease (CAD) is the key element in guiding the work-up of patients with suspected angina. Thickening of the arterial wall is a hallmark of atherosclerosis. Therefore, the main purpose of this study was to determine whether abdominal aortic intima-media thickness (AAIMT), which is the earliest zone of atherosclerotic manifestations, has a predictive value in CAD severity. A total of 255 consecutive patients who were referred for invasive coronary angiography due to suspected stable angina pectoris were prospectively included in the study. B-mode ultrasonography was used to determine AAIMT before coronary angiography. Coronary artery disease severity was assessed with the SYNTAX score (SS). A history of hypertension, age, dyslipidemia, and higher AAIMT (odds ratio: 2.570; 95%CI 1.831-3.608; P < .001) were independent predictors of intermediate or high SS. An AAIMT

The generation of cellularized bioartificial blood vessels resembling all three layers of the natural vessel wall with physiological morphology and cell alignment is a long pursued goal in vascular tissue engineering. Simultaneous culture of all three layers under physiological mechanical conditions requires highly sophisticated perfusion techniques and still today remains a key challenge. Here, three-layered bioartificial vessels based on fibrin matrices were generated using a stepwise molding technique. Adipose-derived stem cells (ASC) were differentiated to smooth muscle cells (SMC) and integrated in a compacted tubular fibrin matrix to resemble the tunica media. The tunica adventitia-equivalent containing human umbilical vein endothelial cells (HUVEC) and ASC in a low concentration fibrin matrix was molded around it. Luminal seeding with HUVEC resembled the tunica intima. Subsequently, constructs were exposed to physiological mechanical stimulation in a pulsatile bioreactor for 72 h. Compared to statically incubated controls, mechanical stimulation induced physiological cell alignment in each layer: Luminal endothelial cells showed longitudinal alignment, cells in the media-layer were aligned circumferentially and expressed characteristic SMC marker proteins. HUVEC in the adventitia-layer formed longitudinally aligned microvascular tubes resembling vasa vasorum capillaries. Thus, physiologically organized three-layered bioartificial vessels were successfully manufactured by stepwise fibrin molding with subsequent mechanical stimulation.

Clinical studies have revealed a greater risk of pulmonary autograft dilation after the Ross procedure in patients with preoperative aortic insufficiency (AI). The present study examined whether the morphologic, biomechanical, and cellular properties of the pulmonary artery (PA) from patients with AI were phenotypically different compared with patients diagnosed with aortic stenosis (AS).PA segments were harvested from patients undergoing the Ross procedure for AS (n = 16) and AI (n = 6). Preoperative aortic annulus was significantly larger (P0.05) in patients with AI (28.5 ± 1.8 mm) vs AS (22.8 ± 1.2 mm). Morphologic, biomechanical, and cellular phenotypes of the PA were analyzed.Collagen and elastin content in the media of the PA wall were similar in patients with AS and AI. Elastic modulus and energy loss of the PA were not significantly different between the groups. In the media of the PA, expression of a panel of vascular smooth muscle cell-specific proteins were similar in patients with AS and AI. In contrast, nonmuscle myosin IIB protein levels in the PA of AS patients were significantly higher compared with AI patients, and immunofluorescence identified staining in α-smooth muscle actin-positive vascular smooth muscle cells.Despite similar morphological and biomechanical properties, the disparate expression of nonmuscle myosin IIB protein distinguishes the PA of patients with AI from patients with AS. The biological role in vascular smooth muscle cells and the potential contribution of nonmuscle myosin IIB to pulmonary autograft dilation in a subset of AI patients after the Ross procedure remain to be determined.

Fibrous membranes played an important role to prepare tubular scaffolds for muscular artery regeneration. In this study, a strategy has been developed to combine silk fibroin (SF) with highly porous electrospun poly(L-lactic acid) (PLLA) fibrous membrane towards vascular scaffolds. After PLLA fibres were electrospun and collected, they were immersed into acetone to generate a porous structure with ultra-high surface area. While the pores on PLLA fibres were fulfilled with SF solution and dried, SF was coated uniformly and tightly on PLLA fibres. A multi-layer tubular structure of the tunica media was simulated by winding and stacking a strip of electrospun fibrous membrane. In vitro viability and morphology studies of A7r5 smooth muscle cells were undertaken for up to 14 days. Because the hydrophilicity of SF/PLLA composite fibres were improved dramatically, it had a positive effect on cell adhesion rate (97%) and proliferation (64.4%). Moreover, good cell morphology was observed via a multiphoton laser confocal microscope on SF/PLLA bioactive materials. These results demonstrated that the hierarchical porous SF/PLLA fibrous membranes are promising off-the-shelf scaffolds for muscular artery regeneration.

Cardiovascular disease (CVD) is a major cause of death in patients with chronic kidney disease (CKD). Both conditions are rising in incidence as well as prevalence, creating poor outcomes for patients and high healthcare costs. Recent data suggests CKD to be an independent risk factor for CVD. Accumulation of uremic toxins, chronic inflammation, and oxidative stress have been identified to act as CKD-specific alterations that increase cardiovascular risk. The association between CKD and cardiovascular mortality is markedly influenced through vascular alterations, in particular atherosclerosis and vascular calcification (VC). While numerous risk factors promote atherosclerosis by inducing endothelial dysfunction and its progress to vascular structural damage, CKD affects the medial layer of blood vessels primarily through VC. Ongoing research has identified VC to be a multifactorial, cell-mediated process in which numerous abnormalities like mineral dysregulation and especially hyperphosphatemia induce a phenotype switch of vascular smooth muscle cells to osteoblast-like cells. A combination of pro-calcifying stimuli and an impairment of inhibiting mechanisms like fetuin A and vitamin K-dependent proteins like matrix Gla protein and Gla-rich protein leads to mineralization of the extracellular matrix. In view of recent studies, intercellular communication pathways via extracellular vesicles and microRNAs represent key mechanisms in VC and thereby a promising field to a deeper understanding of the involved pathomechanisms. In this review, we provide an overview about pathophysiological mechanisms connecting CKD and CVD. Special emphasis is laid on vascular alterations and more recently discovered molecular pathways which present possible new therapeutic targets.

Background: Late failure of arterial aortocoronary conduits may result from abnormal activity of cells found in the vessel wall, including macrophages. The purpose of this study was to assess if there are any associations between the number of macrophages and overexpression of matrix metalloproteinases (MMPs) in the wall of arterial grafts, as well as their clinical significance. Methods: This study involved 128 consecutive patients with a mean age of 64.9 ± 9.7 years who underwent elective surgery for coronary artery disease (CAD). The surplus segments of internal thoracic artery (ITA) and radial arteries (RA) were taken for immunohistochemical analysis of macrophage numbers and MMPs expression. The participants who reached the clinical primary end-point (cardiacrelated death, acute coronary syndrome or progression of CAD) had a follow-up angiography. Results: The mean numbers of macrophages were higher on RA (70 [24; 112]) than ITA cross-sections (44 [24; 59]; p < 0.001). Median expression of both MMP2 and MMP9 were stronger in the ITA than RA cross-sections (p < 0.001). A significant positive correlation of MMP2 expression and a number of macrophages infiltrating the tunica media of arterial segments were noted on both ITA and RA cross-sections. In addition, the arterial segments of the 6 patients who reached clinical end-point had higher numbers of macrophages and stronger MMP2 expression when compared to the rest of the participants. Conclusions: Macrophage infiltration of arterial wall grafts prior to harvesting may be associated with higher risk of late occlusion and MMP2 might be facilitating this process.

Objectives: Patients with bipolar disorder are at high risk of cardiovascular diseases. Among cardiovascular diseases, coronary heart disease and stroke are the leading causes of premature death and both share the pathogenesis of arterial atherosclerosis. Increased carotid intima-media thickness is sensitive for detecting early atherosclerosis and a practical index for predicting cardiovascular diseases. However, few studies investigated carotid intima-media thickness in adults with bipolar disorder. We attempted to determine the factors associated with carotid intima-media thickness in adults with bipolar disorder. Methods: The euthymic out-patients with bipolar I disorder aged over 20 years were recruited to measure the carotid intima-media thickness value through B-mode carotid ultrasound. Those with any psychiatric disorder, acute or life-threatening medical condition were excluded. All clinical information was obtained by reviewing medical records and directly interviewing patients with reliable others. Results: Of the 106 participants with a mean age of 44.5 years, 40.6% ( N = 43) had concurrent cardiovascular/endocrine/metabolic diseases. A multivariate regression indicated that higher assumed daily lithium dosage was significantly associated with a decreased carotid intima-media thickness in the whole sample. In the young subgroup (⩽45 years old, N = 63), higher current daily lithium dosage and lower body mass index were associated with lower carotid intima-media thickness. In those without concurrent cardiovascular/endocrine/metabolic diseases, higher ratio of first-generation antipsychotics exposure in relation to illness chronicity was associated with higher carotid intima-media thickness, after controlling for body mass index or age. Conclusion: Lithium treatment may be associated with less progression in carotid intima-media thickness and the reduced risk for atherosclerosis in adults with bipolar disorder, including those with high cardiovascular disease risk. In addition to age and body mass index, antipsychotics may increase carotid intima-media thickness even in the low cardiovascular disease-risk patients.

Objectives: Ultra-high frequency ultrasonography (UHFUS) is a recently introduced diagnostic technique which finds several applications in diverse clinical fields. The range of frequencies between 30 and 100 MHz allows for high spatial resolution imaging of superficial structures, making this technique suitable for the imaging of skin, blood vessels, musculoskeletal anatomy, oral mucosa, and small parts. However, the current clinical applications of UHFUS have never been analyzed in a consistent multidisciplinary manner. The aim of this study is to revise and discuss the current applications of UHFUS in different aspects of research and clinical practice, as well as to provide some examples of the current work-in-progress carried out in our center. Materials and Methods: A literature search was performed in order to retrieve articles reporting the applications of UHFUS both in research and in clinical settings. Inclusion criteria were the use of frequencies above 30 MHz and study design conducted in vivo on human subjects. Results: In total 66 articles were retrieved. The majority of the articles focused on dermatological and vascular applications, although musculoskeletal and intraoral applications are emerging fields of use. We also describe our experience in the use of UHFUS as a valuable diagnostic support in the fields of dermatology, rheumatology, oral medicine, and musculoskeletal anatomy. Conclusion: Ultra-high frequency ultrasonography application involves an increasing number of medical fields. The high spatial resolution and the superb image quality achievable allow to foresee a wider use of this novel technique, which has the potential to bring innovation in diagnostic imaging.

A micromechanical analysis is offered for the prediction of the global behavior of biological tissues. The analysis is based on the isotropic-hyperelastic behavior of the individual constituents (Collagen and Elastin), their volume fractions, and takes into account their detailed interactions. The present analysis predicts the instantaneous tensors from which the effective current first tangent tensor is established, thus providing the overall anisotropic constitutive behavior of the composite and the resulting field distribution in the composite. This is in contradistinction with the macroanalysis in which the composite internal energy, which involves unknown functions that depend on several strain invariants, must be proposed. The offered micromechanical analysis forms a generalization to the finite strain high-fidelity generalized method of cells (HFGMC) based on the homogenization technique for periodic composites to the parametric finite strain. This involves an arbitrary discretization of the repeating unit-cell of the periodic composites. Results are given for the response of the human abdominal aorta, which consists of three layered tissues: intima, media, and adventitia, all of which are composed out of the Collagen and Elastin. The isotropic-hyperelastic constituents (Mooney-Rivlin and Yeoh) of the composites are calibrated by utilizing available experimental data which describe the response of the tissue. Validation of the results is performed by comparison of the predicted Cauchy stress and stretches with the experimental measurements. In addition, results are given in the form of Cauchy stress and deformation gradient field distributions in the constituents of several tissues.

Background: The impact of hepatitis virus infection on arterial calcification (AC) was not studied. Objective: To study the prevalence, severity and distribution of AC in incident hemodialysis patients with hepatitis B and C viral infection. Cases and methods: 172 stage 5 CKD adults (98 male and 74 female) were included; 58 of them were seronegative for both hepatitis B and C (SN group), 48 were positive for hepatitis B virus infection (HBV group) and 66 were hepatitis C virus positive (HCV group). Beside histopathology of the obtained arterial samples, all these cases were examined for body mass index (BMI), serum calcium (Ca), phosphorus (P), alkaline phosphatase (AP), serum albumin, uric acid (UA), alanine transaminase (ALT), parathormone (PTH), fibroblast growth factor 23(FGF23), interleukin 6 (IL6), and 25 hydroxy vitamin D (25 (OH) vit D), hemoglobin concentration, and serum ferritin. Results: 86 (50%) of the cases had AC; 11 of them were in SN group (19%), 9 in HBV group (18.8%) and all the 66 HCV group (100%). In SN group, 4 had intimal calcification, 5 had medial calcification, and 2 had both intimal and medial calcification. In HBV group, 9 had intimal calcification, while no cases were encountered with either medial or both site calcifications. In HCV group, 16 had intimal calcification, 31 had medial calcification, and 19 had both intimal and medial calcification. Calcification was in the form of spots in one case in SN group, and 6 cases in HBV group, a single plaque of calcification in 5 cases of SN group, 3 cases of HBV group, and 16 cases of HCV group, multiple plaques were detected in 4 cases in SN group, and 31 cases in HCV group, and diffuse calcification in one case in SN group, and 19 cases in HCV group.In HBV group, calcification was only detected in patients with high viremia, while all patients with low or moderate viremia were devoid of calcification. In HCV group, all patients with low viremia had intimal solitary plaque of calcification, all patients with moderate viremia had multiple plaques of medial calcification, while all patients with high viremia had diffuse intimal and medial calcification. Both groups of viral hepatitis were significantly different in comparison to SN group in either distribution or calcification score (P

Understanding the correlation between tissue architecture, health status, and mechanical properties is essential for improving material models and developing tissue engineering scaffolds. Since structural-based material models are state of the art, there is an urgent need for experimentally obtained structural parameters. For this purpose, the medial layer of nine human abdominal aortas was simultaneously subjected to equibiaxial loading and multi-photon microscopy. At each loading interval of 0.02, collagen and elastin fibers were imaged based on their second-harmonic generation signal and two-photon excited autofluorescence, respectively. The structural alterations in the fibers were quantified using the parameters of orientation, diameter, and waviness. The results of the mechanical tests divided the sample cohort into the ruptured and non-ruptured, and stiff and non-stiff groups, which were covered by the findings from histological investigations. The alterations in structural parameters provided an explanation for the observed mechanical behavior. In addition, the waviness parameters of both collagen and elastin fibers showed the potential to serve as indicators of tissue strength. The data provided address deficiencies in current material models and bridge multiscale mechanisms in the aortic media. STATEMENT OF SIGNIFICANCE: Available material models can reproduce, but cannot predict, the mechanical behavior of human aortas. This deficiency could be overcome with the help of experimentally validated structural parameters as provided in this study. Simultaneous multi-photon microscopy and biaxial extension testing revealed the microstructure of human aortic media at different stretch levels. Changes in the arrangement of collagen and elastin fibers were quantified using structural parameters such as orientation, diameter and waviness. For the first time, structural parameters of human aortic tissue under continuous loading conditions have been obtained. In particular, the waviness parameters at the reference configuration have been associated with tissue stiffness, brittleness, and the onset of atherosclerosis.

Aortic aneurysms occur relatively frequently in the ascending thoracic aorta, but are rarely seen in patients with type 2 diabetes. Our aim was to evaluate inflammatory cell infiltration in the ascending aortic aneurysm wall in patients with diabetes without arterial hypertension (DM2 group, N=6) versus hypertensive non-diabetic patients (AH group, N=34). For histologic analysis, the sections were stained with hematoxylin-eosin and Movat pentachrome. The immunohistochemical staining was used to analyze the infiltration of pro-inflammatory (CD68) and anti-inflammatory macrophages (CD163), T helper (CD4) and T killer cells (CD8), and B (CD79a) and plasma cells (CD138) in all three layers of aneurysms of both groups. The statistical significance of the differences between groups was evaluated by ANOVA and the Welch test. In comparison to the AH group, the DM2 group developed less severe infiltration of pro-inflammatory macrophages (P=0.004) and B cells (P=0.025) in the tunica intima, and tunica media (P=0.049, P=0.007, respectively), and fewer plasma cells in the tunica media (P=0.024) and tunica adventitia (P=0.017). We found no significant differences in the number of T helper, T killer cells, and anti-inflammatory macrophages and in the amount of collagen and elastic fibers, ground substance, and smooth muscle cells in all three layers of the vessel wall. Except in tunica adventitia of DM2 group, there were more collagen fibers overall (P=0.025). Thus, we conclude that the histological structure of the aneurysm in diabetics without hypertension is almost the same as in hypertensive patients without diabetes. Diabetics had significantly less inflammatory infiltration in all three layers of the vessel wall, and more collagen fibers in tunica adventitia.

Endothelial–mesenchymal transition (EndMT) is a form of endothelial dysfunction wherein endothelial cells acquire a mesenchymal phenotype and lose endothelial functions, which contributes to the pathogenesis of intimal hyperplasia and atherosclerosis. The mitogen activated protein kinase 7 (MAPK7) inhibits EndMT and decreases the expression of the histone methyltransferase Enhancer-of-Zeste homologue 2 (EZH2), thereby maintaining endothelial quiescence. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 that methylates lysine 27 on histone 3 (H3K27me3). It is elusive how the crosstalk between MAPK7 and EZH2 is regulated in the endothelium and if the balance between MAPK7 and EZH2 is disturbed in vascular disease. In human coronary artery disease, we assessed the expression levels of MAPK7 and EZH2 and found that with increasing intima/media thickness ratio, MAPK7 expression decreased, whereas EZH2 expression increased. In vitro, MAPK7 activation decreased EZH2 expression, whereas endothelial cells deficient of EZH2 had increased MAPK7 activity. MAPK7 activation results in increased expression of microRNA (miR)-101, a repressor of EZH2. This loss of EZH2 in turn results in the increased expression of the miR-200 family, culminating in decreased expression of the dual-specificity phosphatases 1 and 6 who may repress MAPK7 activity. Transfection of endothelial cells with miR-200 family members decreased the endothelial sensitivity to TGFβ1-induced EndMT. In endothelial cells there is reciprocity between MAPK7 signaling and EZH2 expression and disturbances in this reciprocal signaling associate with the induction of EndMT and severity of human coronary artery disease.

Inflammatory aortic diseases are broadly classified into three categories according to the degree of inflammation: atherosclerosis, atherosclerosis with excessive inflammation, and aortitis/periaortitis. This paper presents a case of a 39-year old man with aneurysmal dilatation of thoracic aorta and aortic valve insufficiency. The aortic wall showed thickening and wrinkled "tree bark" appearance as well as apparent scarring of the intima. Histological examination revealed intimal hyperplasia, a granulomatous/giant cell pattern in the inner tunica media, a few epithelioid macrophages, abundant chronic lymphoplasmacytic and histiocytic inflammation and discrete fibrinoid necrosis. The histological findings were indicative of Horton's disease, but no typical clinical features were present. The case illustrates the difficulties involved in diagnosing inflammatory aortic diseases where it may be challenging to arrive at a specific diagnosis despite the knowledge of medical history, and available macroscopic and histological findings.

Aortic mechanical and structural characteristics have profound effects on pathophysiology, but many aspects of physiologic stress-stretch state and intramural changes due to aging remain poorly understood in human tissues. While difficult to assess in vivo due to residual stresses and pre-stretch, physiologic stress-stretch characteristics can be calculated using experimentally-measured mechanical properties and constitutive modeling. Mechanical properties of 76 human descending thoracic aortas (TA) from 13 to 78-year-old donors (mean age 51±18 years) were measured using multi-ratio planar biaxial extension. Constitutive parameters were derived for aortas in 7 age groups, and the physiologic stress-stretch state was calculated. Intramural characteristics were quantified from histological images and related to aortic morphometry and mechanics. TA stiffness increased with age, and aortas became more nonlinear and anisotropic. Systolic and diastolic elastic energy available for pulsation decreased with age from 30 to 8 kPa and from 18 to 5 kPa, respectively. Cardiac cycle circumferential stretch dropped from 1.14 to 1.04, and circumferential and longitudinal physiologic stresses decreased with age from 90 to 72 kPa and from 90 to 17 kPa, respectively. Aortic wall thickness and radii increased with age, while the density of elastin in the tunica media decreased. The number of elastic lamellae and circumferential physiologic stress per lamellae unit remained constant with age at 102±10 and 0.85±0.04 kPa, respectively. Characterization of mechanical, physiological, and structural features in human aortas of different ages can help understand aortic pathology, inform the development of animal models that simulate human aging, and assist with designing devices for open and endovascular aortic repairs. Statement of significance This manuscript describes mechanical and structural changes occurring in human thoracic aortas with age, and presents material parameters for 4 commonly used constitutive models. Presented data can help better understand aortic pathology, inform the development of animal models that simulate human aging, and assist with designing devices for open and endovascular aortic repairs.

Background Segmental arterial mediolysis (SAM) is a rare non-atherosclerotic, noninflammatory vascular disease, characterized by mediolysis. We report an extremely rare case of subarachnoid hemorrhage (SAH) due to a ruptured blood blister–like aneurysm (BBA) of the internal carotid artery associated with SAM-related arteriopathy. Case Description We experienced a case of SAH followed by intraperitoneal hemorrhage that occurred 12 days after the SAH onset. SAH was caused by a ruptured BBA of the internal carotid artery, which was treated by trapping with high-flow bypass. Intraperitoneal hemorrhage was caused by a rupture of a posterior inferior pancreaticoduodenal artery (PIPDA) aneurysm, which induced hypovolemic shock resulting in death in spite of endovascular internal trapping. Postmortem pathologic examination revealed that the PIPDA pseudoaneurysm was due to SAM. Conclusions We should pay attention to the association of SAM, which is a potentially life-threatening pathology when treating cerebral BBAs.

Normally, smooth muscle cells (SMCs) are localized in the tunica media of the vasculature, where they take responsibility for vascular contraction and extracellular matrix (ECM) generation. SMCs also play a significant role in obedience and elastic rebound of the artery in response to the haemodynamic condition. However, under pathological or stressed conditions, phenotype switching from contractile to synthetic state or other cell types will occur in SMCs to positively or negatively contribute to disease progression. Various studies demonstrated that functional changes of SMCs are implicated in several cardiovascular diseases. In this review, we present the function of vascular SMCs (VSMCs) and the involved molecular mechanisms about phenotype switching, and summarize the roles of SMCs in atherosclerosis, hypertension, arterial aneurysms and myocardial infarction, hoping to obtain potential therapeutic targets against cardiovascular disease in the clinical practices.

BACKGROUND The aim of our study is to investigate the effects of urotensin-II (U-II) on the left internal mammary artery (LIMA) wall and role of U-II in atherosclerotic processes affecting the long-term patency of LIMA. METHOD Patients were divided into 2 groups, namely Group I: patients with coronary artery disease (CAD) and Group II: DM + CAD. The patients were evaluated by Gencini scoring before coronary artery bypass grafting (CABG). Routine tissue follow-up, hemotoxylin-eosin staining and immunoreactivity with U-II were observed. Then, vessel damage score, H-Score and LIMA layer thickness were calculated and evaluated statistically. RESULTS On light microscopic examination, the LIMA total damage score in DM + CAD group was significantly higher compared to the control group. The assessment of H score revealed that U-II was more intense in tunica intima and tunica media in the DM+CAD group as compared to the control group (p < 0.05). Furthermore, tunica intima and tunica media in the DM + CAD group were thicker than in the control group (p < 0.05). CONCLUSIONS We found that U-II is effective in atherosclerotic processes of arterial grafts. The DM + CAD group has high U-II density with high total damage score in intima and media layers of LIMA. U-II may be effective in late survival results after CABG (Tab. 3, Fig. 2, Ref. 19).

There are substantial data in support of improved patency using the no-touch (NT) saphenous vein (SV) harvesting technique. However, wound complications correlated with such are more significant than those associated with the skeletonized technique. To solve this, we introduced the use of the electrothermal bipolar vessel sealing device via small incisions. In this study, a cordless retractor with a built-in LED light source was utilized. The NT-SV graft was harvested with a pedicle of surrounding tissue approximately 5 mm in size and attached to the main trunk. The intima, tunica media, adventitia, and vasa vasorum appeared normal by histological analysis. Our technique combines the potential advantages of a minimally invasive endoscope approach using bipolar electrothermy and the improved patency of a NT-SV.

Background Segmental arterial mediolysis (SAM) is a poorly understood, nonatherosclerotic, noninflammatory disease resulting from arterial medial degeneration. Patients may present with aneurysm, dissection, stenosis, or bleeding from visceral or renal arteries. Treatment algorithms are poorly characterized. Methods A retrospective review of all patients diagnosed with SAM was performed at our institution. Patients were identified by established criteria that include clinical presentation in combination with radiographic and serologic findings. Demographics, presenting symptoms, diagnostic evaluation, management, and outcomes were reviewed. Results There were 117 patients diagnosed with SAM between 2000 and 2016; 67.5% (n = 79) were male. Mean age was 52.7 years (range, 23.4-90 years); 69.2% (n = 81) presented with acute abdominal pain, 22.2% (n = 26) with flank pain, and 19.7% (n = 23) with back pain; 15.4% (n = 18) had abdominal pain longer than 30 days; 13.7% (n = 16) had acute hypertension, and 5.1% (n = 6) were hypotensive; 10.3% (n = 12) were asymptomatic. There were 93 (79.5%) dissections and 61 (52.1%) aneurysms. Hemorrhage was seen in 10 (8.5%). The celiac axis was affected in 54.7% (n = 64), renal arteries in 49.6% (n = 5 8), superior mesenteric artery in 43.6% (n = 51), and inferior mesenteric artery in 2.6% (n = 3). After diagnosis of SAM, aspirin was prescribed in 60.7% (n = 71). Statins were prescribed in 29.9% (n = 35). Antihypertensive medications were prescribed in 65% (n = 76), including beta blockers in 42.7% (n = 50); 40.2% (n = 47) of patients were prescribed anticoagulation. Interventions were performed in 26 (22%) patients; 13 had endovascular intervention only, 9 open surgery only, and 4 open and endovascular interventions. Of the 17 patients undergoing endovascular intervention, 19 procedures were performed, most commonly embolization (78.9% [n = 15]), followed by stenting (10.5% [n = 2]). Of the 13 patients undergoing open surgery, 14 procedures were performed, including arterial bypass (50% [n = 7]) and splenectomy with aneurysm ligation (15.4% [n = 2]). Other surgery involved thrombectomy (21.4% [n = 3]) and angioplasty (14.3% [n = 2]). Only 11.5% (n = 3) experienced a perioperative complication, including one hematoma, one abscess, and one death secondary to ongoing hemorrhage. Follow-up imaging was performed in 96.6% (n = 112). Mean follow-up was 1258 days (range, 2-5017 days). Of these, 27.7% (n = 31) had regression, 43.8% (n = 49) stability, and 28.6% (n = 32) progression. Average time between initial diagnosis and progression was 666 days. Conclusions SAM is an uncommon disease that may require intervention; it is therefore important that the vascular surgery community be aware of this disease. Follow-up imaging is required to monitor for disease progression.

The generalized fractional Maxwell model, formulated for hyperelastic material within the framework of the nonlinear viscoelasticity with internal variables, is applied to identify viscoelastic constitutive equations from layer-specific experimental data obtained by uniaxial harmonic loading of ex-vivo human descending thoracic aortas. The constitutive parameters are identified by using a genetic algorithm for the optimal fitting of the experimental data. The accuracy of the fitted fractional model is compared to the fitted integer order model with the same number of Maxwell elements. The formulation of an original strain energy density function for anisotropic nonlinear viscoelasticity is introduced and constitutive parameters are obtained from the experiments.

Background: Intravascular ultrasound (IVUS) provides axial grey-scale images of blood vessels. The large number of images require automatic analysis, specifically to identify the lumen and outer vessel wall. However, the high amount of noise, the presence of artifacts and anatomical structures, such as bifurcations, calcifications and fibrotic plaques, usually hinder the proper automatic segmentation of the vessel wall. Methods: Lumen, media, adventitia and surrounding tissues are automatically detected using Support Vector Machines (SVMs). The classification performance of the SVMs vary according to the kind of structure present within each region of the image. Random Forest (RF) is used to detect different morphological structures and to modify the initial layer classification depending on the detected structure. The resulting classification maps are fed into a segmentation method based on deformable contours to detect lumen-intima (LI) and media-adventitia (MA) interfaces. Results: The modifications in the layer classifications according to the presence of structures proved to be effective improving LI and MA segmentations. The proposed method reaches a Jaccard Measure (JM) of 0.88 ± 0.08 for LI segmentation, compared with 0.88 ± 0.05 of a semiautomatic method. When looking at MA, our method reaches a JM of 0.84 ± 0.09, and outperforms previous automatic methods in terms of HD, with 0.51mm ± 0.30. Conclusions: A simple modification to the arterial layer classification produces results that match and improve state-of-the-art fully-automatic segmentation methods for LI and MA in 20MHz IVUS images. For LI segmentation, the proposed automatic method performs accurately as semi-automatic methods. For MA segmentation, our method matched the quality of state-of-the-art automatic methods described in the literature. Furthermore, our implementation is modular and open-source, allowing for future extensions and improvements. Fil: Lo Vercio, Lucas. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Grupo de Plasmas Densos Magnetizados. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Grupo de Plasmas Densos Magnetizados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; Argentina Fil: del Fresno, Mirta Mariana. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Grupo de Plasmas Densos Magnetizados. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Grupo de Plasmas Densos Magnetizados; Argentina Fil: Larrabide, Ignacio. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Grupo de Plasmas Densos Magnetizados. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Grupo de Plasmas Densos Magnetizados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; Argentina

Aim To investigate if calcification and intimal media thickness (IMT) of arteries are present in children and adolescents with end-stage renal disease and to describe the risk factors associated with these alterations. Methods In an observational, cross-sectional prospective study, 68 patients were evaluated at the time of renal transplantation. A fragment of the inferior epigastric artery was removed during surgery for histopathological analysis to verify the presence or not of arterial calcification. Two outcomes were considered: the presence of calcium deposition and the measurement of the IMT of the artery. The potential exposure variables were: age, chronic kidney disease aetiology, diagnosis time, systolic blood pressure (SBP), use of oral active vitamin D, homocysteine and C-reactive protein. Results No arterial calcification was observed in the studied sample. The median value of the IMT of the inferior epigastric artery was 166 μm (interquartile range = 130-208). SBP standard deviation score and age were the only factors associated with this outcome. There was no statistical interaction between SBP and age with the IMT (P = 0.280). Conclusion Arterial calcification is rare in children and adolescents with end-stage renal disease. The factors associated with IMT were age and SBP.

Segmental arterial mediolysis (SAM) is a rare non-atherosclerotic, non-inflammatory, non-infectious arteriopathy in middle-aged patients that tends to affect medium-sized splanchnic arteries typically leading to dissecting aneurysms which in case of rupture have a high mortality. Treatment options include watchful waiting and endovascular or surgical intervention. There are no official treatment guidelines and to the best of our knowledge, there has not been any report of extensive exclusion of multiple splanchnic vessel regions in affected patients to date. We retrospectively examined the outcome of extensive splanchnic embolization in four patients suffering from SAM between 2011 and 2016 with follow-up periods of up to 7 years. One patient presented with abdominal pain due to rupture of aneurysms of the pancreaticoduodenal arcade, one with abdominal pain due to dissection, and two were clinically asymptomatic but displayed rapidly progressing disease over the course of 12 months. All patients were treated with complete exclusion of the diseased vessel segments by coiling all branches to and from the diseased segment. In three cases the main hepatic artery was excluded completely. In one case, the complete vascular bed of the celiac axis was excluded by coiling the distal vessel branches and placing a stent graft over the orifice of the celiac trunk. During a follow-up period of a minimum of 2 and a maximum of 7 years after intervention, there were no immediate or long-term complications except for a temporary arterio-portal fistula. Interestingly, no new diseased areas of SAM were detected afterwards. Extensive endovascular exclusion of the entire diseased arterial segment with coils seems to be a safe and effective treatment option in patients with SAM presenting with ruptured or rapidly growing aneurysms. Provided that patients have normal liver function and proper portal venous flow, risk of hepatobiliary complications seems to be low even after extensive embolization. · An asymptomatic SAM can be followed up.. · In case of disease progression or suspicion of aneurysm rupture, an endovascular approach is indicated where the whole pathological vessel bed should be excluded with coils.. · It seems that exclusion of even extensive vessel areas is tolerated..· Najafi A, Sheikh GT, Binkert C. Extensive Embolization of Splanchnic Artery Aneurysms due to Segmental Arterial Mediolysis. Fortschr Röntgenstr 2019; 191: 1010 - 1014.ZIEL: Die segmentale arterielle Mediolyse (SAM) ist eine seltene, nicht-atherosklerotische, nicht-inflammatorische und nicht-infektiöse Arteriopathie des mittleren Lebensalters, die vorwiegend mittelgroße Viszeralarterien betrifft und typischerweise zu dissezierten Aneurysmata führt, welche im Falle einer Ruptur mit einer hohen Mortalität einhergehen. Als Therapieoptionen kommen in Frage das „watchful waiting“, eine endovaskuläre oder eine chirurgische Intervention. Zurzeit existieren keine offiziellen Richtlinien. Unseres Wissens nach existieren keine Untersuchungen über ausgedehnte Embolisationen mehrerer Viszeralgefäße in dieser Patientengruppe. Wir haben retrospektiv das Resultat extensiver viszeraler Embolisationen bei vier Patienten zwischen 2011 und 2016 untersucht mit Langzeit Follow-Up von bis zu 7 Jahren. Ein Patient präsentierte sich mit Ruptur von Aneurysmen der pancreatico-duodenalen Arkade, ein Patient mit dem Bild eines akuten Abdomens infolge einer Dissektion und zwei Patienten waren asymptomatisch. Die drei Letztgenannten zeigten unter engmaschiger Verlaufskontrolle (bis 12 Monate) einen Progress. Alle Patienten wurden endovaskulär behandelt, wobei jeweils das gesamte erkrankte Versorgungsgebiet, sowohl zuführende als auch abführende Gefäße, mittels Coils ausgeschaltet wurde. In drei von vier Fällen wurden alle hepatischen Arterien gecoilt. Bei einem Patienten wurde das gesamte Stromgebiet des Truncus coeliacus ausgeschaltet mittels Coiling der distalen Gefäße und Stentgraft des Truncusabgangs. Post-interventionell zeigten sich nach einem Follow-Up-Intervall von 2 bis 7 Jahren bis auf eine temporäre arterio-portale Fistel keine weiteren Kurzzeit- oder Langzeitkomplikationen. Interessanterweise entwickelten sich zudem nach dem akuten Krankheitsschub keine neuen Aneurysmata. Das endovaskuläre Ausschalten auch größerer viszeraler Versorgungsgebiete scheint eine sichere und effektive Behandlungsoption bei Patienten mit rupturierter oder progredienter SAM zu sein. Unter der Voraussetzung einer normalen Leberfunktion mit regelrechtem portalvenösem Fluss dürfte die hepatobiliäre Komplikationsrate, auch nach extensiver Embolisation, gering sein.· Eine asymptomatische SAM kann primär beobachtet werden.. · Bei Größenprogredienz der Aneurysmata oder Verdacht auf Ruptur ist eine endovaskuläre Therapie angezeigt, dabei soll das gesamte pathologische Gefäßgebiet mit Coils ausgeschaltet werden.. · Es scheint, dass auch der Ausschluss größerer Gefäßareale toleriert wird..· Najafi A, Sheikh GT, Binkert C. Extensive Embolization of Splanchnic Artery Aneurysms due to Segmental Arterial Mediolysis. Fortschr Röntgenstr 2019; 191: 1010 – 1014.

Angioleiomyomas (ALMAs) are benign tumors that arise from smooth muscle cells that form the tunica media of vascular structures. To our knowledge, only five cases of ALMA of the external auditory canal (EAC) have been reported. We report the case of a 52-year-old man with left otalgia, otorrhea, auricular fullness, and hearing loss. On otomicroscopic examination, a reddish and smooth mass completely occluding the EAC was seen. Computed tomography scan showed a soft tissue mass with a complete opacification of the left EAC. A possible diagnosis of ALMA should be considered when finding a tumor inside the external ear canal. An accurate pathological examination should be performed to differentiate benign vascular ALMA from malignant leiomyosarcomas. Complete surgical excision is the treatment of choice in benign tumors.

Background Various investigations have reported that the internal mammary artery (IMA) is an efficient and functional choice of conduit for vascular graft surgeries, especially for coronary artery bypass grafts; however, the quest to find an ideal vascular substitute remains. We hypothesized that acellular IMA could be an appropriate graft for small-diameter vascular bypasses that could be used in various surgeries including coronary artery bypass grafting. Methods We decellularized human IMAs and performed histologic evaluations and scanning electron microscopy to confirm the decellularization process and the preservation of the extracellular matrix. Subsequently, we grafted the scaffolds into the superficial femoral arteries of 8 New Zealand rabbits with an end-to-end anastomosis. Computed tomography angiograms were provided at 3, 12, and 36 months postoperatively. Subsequently, the animals were killed, and biopsies were taken for histologic and immunohistochemical assessments. Results Evaluation of the acellular tissue confirmed the efficacy of the decellularization protocol and the preservation of the extracellular matrix. All 8 animals survived the entire follow-up period. Doppler ultrasonography and computed tomography angiographies verified the conduit's patency. Histologic assessments depicted the recellularization of all 3 layers of the scaffold. Smooth muscle cells were detected in tunica media. Immunohistochemical assessments confirmed these findings. Conclusions In conclusion, we demonstrated that acellular human IMA could be used as an efficient small-diameter vascular substitute with high patency. These findings could pave the path for future investigations on the clinical application of acellular IMA as a novel vascular graft for small-diameter bypass surgeries.

Biological aging occurs as a result of the interaction between genetics, chronological age and external factors. It is the basis for new concepts of vascular aging, whose progression is determined by the difference between biological and chronological age. From the structural point of view, the effects of vascular aging are more evident in the tunica media of large elastic arteries, marked by increased arterial stiffness, lumen dilation and wall thickness. These effects are described in the continuum of cardiovascular aging (proposed by Dzau in 2010), in which the progressive steps of microvasculature lesions of the heart, kidney and brain are initiated from the aging process. The increase of arterial stiffness can be detected by several non-invasive methods. Cardiovascular events have been traditionally described using scores that combine conventional risk factors for atherosclerosis. In the classic cardiovascular continuum (Dzau, 2006), to determine the exact contribution of each risk factor is challenging; however, since arterial stiffness reflects both early and cumulative damage of these cardiovascular risk factors, it is an indicator of the actual damage to the arterial wall. This article provides a general overview of pathophysiological mechanisms, arterial structural changes, and hemodynamic consequences of arterial stiffness; non-invasive methods for the assessment of arterial stiffness and of central blood pressure; the cardiovascular aging continuum, and the application of arterial stiffness in cardiovascular risk stratification.O envelhecimento biológico é reflexo da interação entre genética, idade cronológica e fatores externos; é a base para novos conceitos em envelhecimento vascular, cuja progressão é determinada pela diferença entre idade biológica e cronológica. Do ponto de vista estrutural, os efeitos do envelhecimento vascular são mais evidentes na camada média das grandes artérias elásticas e resultam em aumento da rigidez arterial, da dilatação do lúmen e da espessura da parede. Esses efeitos são descritos no continuum de envelhecimento cardiovascular (proposto por Dzau em 2010) em que as etapas progressivas de lesões da microvasculatura de coração, rins e cérebro, têm início a partir do processo de envelhecimento. O aumento da rigidez arterial pode ser verificado de forma não invasiva por vários métodos. Os eventos cardiovasculares têm sido tradicionalmente previstos utilizando escores que combinam fatores de risco convencionais para aterosclerose. No continuum cardiovascular clássico (Dzau, 2006), é desafiador avaliar o peso exato da contribuição de cada fator de risco; entretanto, por refletir o dano precoce e cumulativo desses fatores de riscos cardiovascular, a rigidez arterial reflete o verdadeiro dano à parede arterial. Este artigo fornece uma visão geral dos mecanismos da fisiopatogenia, alterações estruturais das artérias e consequências hemodinâmicas do envelhecimento arterial; métodos não invasivos para a avaliação da rigidez arterial e da medida central da pressão arterial; o continuum de envelhecimento cardiovascular, e aplicação do conceito de rigidez arterial na estratificação de risco cardiovascular.

Transcatheter aortic valve implantation (TAVI) represents a catheter-based and minimally invasive replacement of the aortic valve. TAVI is considered to be a relatively safe procedure and has evolved to a standard procedure in inoperable and high-risk patients with aortic stenosis. We present a case of an octogenarian who died in hospital less than a day after an initially satisfactory TAVI. Cardiologists suspected a combination of cardiogenic and hemorrhagic shock as the cause of death. Autopsy showed rupture of an extensive aortic dissection, which had developed within 24 h after the procedure. The cause of death was eventually defined as internal bleeding due to a rapid two-stage vascular process. The manner of death was considered accidental because an iatrogenic vessel injury beyond the aortic arch was causative for the death. This unusual case highlights the potential for rare, but fatal, complications within the scope of cardiac catheterizations, such as TAVI. Additionally, our findings suggest that these complications need to be recognized in the diagnostic process and management of post-interventional complications.

Medial degeneration is a common histopathological finding in aortopathy and is considered a mechanism for dilatation. We investigated if medial degeneration is specific for sporadic thoracic aortic aneurysms versus nondilated aortas. Specimens were graded by pathologists, blinded to the clinical diagnosis, according to consensus histopathological criteria. The extent of medial degeneration by qualitative (semi-quantitative) assessment was not specific for aneurysmal compared to nondilated aortas. In contrast, blinded quantitative assessment of elastin amount and medial cell number distinguished aortic aneurysms and referent specimens, albeit with marked overlap in results. Specifically, the medial fraction of elastin decreased from dilution rather than loss of protein as cross-sectional amount was maintained while the cross-sectional number, though not density, of smooth muscle cells increased in proportion to expansion of the media. Furthermore, elastic lamellae did not thin and interlamellar distance did not diminish as expected for lumen dilatation, implying a net gain of lamellar elastin and intralamellar cells or extracellular matrix during aneurysmal wall remodeling. These findings support the concepts that: (1) medial degeneration need not induce aortic aneurysms, (2) adaptive responses to altered mechanical stresses increase medial tissue, and (3) greater turnover, not loss, of mural cells and extracellular matrix associates with aortic dilatation.

Objective: The present study explores three-dimensional microscope integrated extravascular OCT as the first suitable intraoperative imaging modality of cerebral aneurysm (CA) and parent vessel wall morphology. Methods: Incidental CAs (n=16) of the anterior circulation with indication for [for full text, please go to the a.m. URL], 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Background The underlying pathophysiology of coronary artery spasm (CAS) remains unclear. We aim to determine whether coronary artery medial layer thickness is associated with CAS using optical coherence tomography. Methods and Results A total of 50 patients with previous myocardial infarction underwent optical coherence tomography of the left anterior descending artery: 20 with CAS and 30 without CAS. Intimal and medial layer areas were measured by planimetric analysis of optical coherence tomography images. The medial area/external elastic membrane (EEM) area was significantly greater in patients with than without CAS (0.13±0.01 versus 0.09±0.01, respectively, P y =−1.85 x 2 +0.81 x +0.01, R 2 =0.43, P y =2993.2 x 2 −1359.6 x +117.1, R 2 =0.53, P Conclusions The structural thickness of the coronary medial layer was increased in patients with CAS, which may provide mechanistic insight into the pathogenesis of CAS. Registration URL: https://www.upload.umin.ac.jp ; Unique identifier: UMIN000018432.

Background Coronary artery aneurysm (CAA) is an important complication of Kawasaki disease (KD) that is associated with arterial structure damage. However, few studies have examined structural changes in coronary arteries that are not associated with CAA. Methods We examined coronary arteries in KD patients with CAAs who underwent follow-up coronary angiography (CAG) and optical coherence tomography (OCT). Coronary arterial branches with no abnormal findings during the most recent CAG were classified into two groups. Arteries with an acute-phase CAA that later regressed were classified as group R; arteries with no abnormal findings on either acute or convalescent phase CAG were classified as group N. Coronary arterial wall structural changes were compared between groups using OCT. Results Fifty-seven coronary arterial branches in 23 patients were evaluated by OCT. Thirty-six branches showed no abnormality during the most recent CAG. Both groups R and N comprised 18 branches. Maximum intimal thicknesses in groups R and N were 475 and 355 µm, respectively (p = 0.007). The incidences of media disruption were 100% and 67%, respectively (p = 0.02). Calcification, macrophage accumulation, and thrombus were not found in either group. Conclusions Intimal thickening and disruption of the media occur in coronary arteries with acute phase CAAs that later regress in the convalescent phase, as well as in arteries with normal CAG findings in the acute and convalescent phases.

BACKGROUND Paclitaxel-coated balloon angioplasty for de-novo coronary artery lesions causes late lumen enlargement (LLE), however, the mechanisms and predictors of LLE have not been elucidated. METHODS AND RESULTS We retrospectively analyzed 91 consecutive patients with 95 de-novo coronary lesions, who underwent paclitaxel-coated balloon angioplasty without stenting from August 2018 to July 2019 as well as follow-up coronary angiography and optical coherence tomography (OCT). The mean follow-up duration was 8.2 ± 2.9 months. The target lesion revascularization rate was 7.3%. OCT demonstrated LLE in 50.5% of lesions. The lesions with LLE had a higher incidence of vessel enlargement (76.6 vs. 29.2%, p

Objective: To elucidate the effect of diabetes mellitus (DM) on the atherosclerotic process in saphenous vein grafts by determining urotensin-II (U-II) levels in harvested saphenous veins of patients who underwent coronary artery bypass grafting (CABG). Methods: Coronary artery disease (CAD) patients who underwent CABG were divided into two groups: Group I (eight non-diabetic patients; CAD group) and Group II (13 patients; DM+CAD group). All patients underwent coronary angiography prior to surgery and Gensini score was used to determine the severity of coronary atherosclerosis. Saphenous vein samples were stained with hematoxylin-eosin and U-II, then damage score, H-Score, and vein layer thicknesses were calculated and statistically evaluated. Results: In light microscopic evaluation, significant difference was observed between the groups in terms of endothelial cells damage, internal elastic lamina degradation, and tunica media vascular smooth muscle cells (VSMCs) damage (P

RationaleThe rupture of the fibrous cap in atherosclerotic lesions is the underlying cause of most thrombi leading to heart attack and a frequent cause of stroke. Caps are produced by smooth muscle cells (SMCs) that are recruited to the subendothelial space. We hypothesized that the recruitment mechanisms are likely common to embryonic artery development, which relies prominently on Notch signaling to form the subendothelial layers of medial SMCs.ObjectiveTo analyze the causal roles of the Notch signaling pathway in SMCs for atherogenesis and cap formation.Methods and ResultsNotch elements involved in arterial media development were found expressed in regions of fibrous cap in mouse plaques. To assess the causal role of Notch signaling in cap formation, we studied atherosclerosis in mice in which the Notch pathway was inactivated specifically in SMCs by conditional knockout of the essential effector transcription factor RBPJ. No major effects were observed on plaque size, but the presence of cap SMCs was significantly reduced. Lineage tracing revealed that the accumulation of SMC-derived plaque cells in the cap region was unaltered but that Notch-defective cells failed to re-acquire the SMC phenotype in the cap. To analyze whether the accumulation of SMC-derived cells in atherogenesis requires down-regulation of Notch signaling, we studied atherosclerosis in mice with constitutive Notch signaling in SMCs achieved by conditional expression of the Notch intracellular domain. Forced Notch signaling inhibited the ability of medial SMCs to contribute to plaque cells, including both cap SMCs and osteochondrogenic cells, and significantly reduced atherosclerosis development.ConclusionsSequential loss and gain of Notch signaling is needed to build the cap SMC population. The shared mechanisms with embryonic arterial media assembly suggest that the fibrous cap forms as a neo-media that restores the connection between endothelium and stabilizing SMCs, which is transiently disrupted by atherogenesis.

Coronary ectasia is a rare vessel defect that represents a pathological and incidental finding in routine coronary angiography performed for other coronary syndromes. This defect exposes to the risk of intra-coronary thrombosis by blood stasis due to the turbulent blood flow in those dilated areas that can lead to sudden death. We report an autopsy case of a male subject suddenly deceased. A medico-legal autopsy concluded an ischemic heart failure due to a vascular thrombosis by a blood clot in a coronary ectasia. Our case report aimed to discuss the mechanisms of sudden death attributed to coronary artery ectasia.

Objective: There is no medical treatment to prevent abdominal aortic aneurysm (AAA) growth and rupture, both of which are linked to smoking. Our objective was to map the tunica-specific pathophysiology of AAA with consideration of the intraluminal thrombus, age, and sex, and to subsequently identify which mechanisms were linked to smoking and diameter growth rate. Approach and Results: Microarray analyses were performed on 246 samples from 76 AAA patients and 13 controls. In media and adventitia, there were 5889 and 2701 differentially expressed genes, respectively. Gene sets related to adaptive and innate immunity were upregulated in both tunicas. Media-specific gene sets included increased matrix disassembly and angiogenesis, as well as decreased muscle cell development, contraction, and differentiation. Genes implicated in previous genome-wide association studies were dysregulated in media. The intraluminal thrombus had a pro-proteolytic and proinflammatory effect on the underlying media. Active smoking resulted in increased inflammation, oxidative stress, and angiogenesis in all tissues and enriched lipid metabolism in adventitia. Processes enriched with active smoking in control aortas overlapped to a high extent with those differentially expressed between AAAs and controls. The AAA diameter growth rate (n=24) correlated with T- and B-cell expression in media, as well as lipid-related processes in the adventitia. Conclusions: This tunica-specific analysis of gene expression in a large study enabled the detection of features not previously described in AAA disease. Smoking was associated with increased expression of aneurysm-related processes, of which adaptive immunity and lipid metabolism correlated with growth rate.

Introduction Diabetes Mellitus (DM) has been known to be a risk factor for the development of more severe form of saphenous vein graft disease after coronary artery bypass grafting (CABG). We aimed to evaluate the impact of type II-DM on histopathological features of great saphenous vein grafts of patients undergoing CABG. Patients and methods Forty consecutive patients undergoing elective CABG were enrolled into the study. Patients were grouped into two; Diabetic group (n = 20); includes patients with preoperative diagnosis of type II-DM and Nondiabetic group (n = 20): those without type II-DM. In all patients, a short segment of the great saphenous vein graft at the level of medial malleolus was taken for light microscopy and transmission electron microscopy (TEM) evaluation. Moreover, immunoexpressions of Caveolin-1, Vascular cell adhesion protein 1 (VCAM-1) and endothelial nitric oxide synthase (eNOS) were studied. Results There were no differences in the demographics of patients between two groups. The magnitude of intimal fibrosis in diabetic group was slightly higher than in nondiabetics (1.95 ± 0.99 versus 1.3 ± 0.8, P = .04). In TEM, vacuolization in endothelial cells, substance accumulation along with coarse collagen fibers and cytoplasmic degeneration with vacuolization in muscle cells were detected in diabetic group. While there were no differences in Caveolin-1 and VCAM-1 immunostaining, the intensity of positive eNOS immunostaining was significantly higher in endothelium (2.10 ± 0.64 versus 1.55 ± 0.68, P = .01) and tunica media 1.75 ± 0.63 versus 1.2 ± 0.52, P = .007) in nondiabetic group, respectively) compared with diabetic group. Conclusion Type II DM might be a reason for decreased expression of eNOS and increased intimal fibrosis, vacuolization of endothelial and smooth muscle cells in saphenous vein grafts. The clinical implications of these alterations on the graft patency need to be evaluated.

Background Kawasaki disease (KD) is a systemic vasculitis syndrome that occurs most frequently in children. Most clinical and pathological studies have focused on its coronary artery lesions. To date, no detailed studies of the aorta have been conducted. We studied KD autopsy cases with the aims of clarifying the time-course of changes in aortic lesions, the differences in the inflammatory cells and degree of inflammation at various aortic sites, and the progression of the inflammation. Materials and Methods The study materials were aortic specimens taken from 37 KD autopsy cases (acute phase: 19; remote phase: 18). Twenty-seven of the cases also had coronary aneurysms. We chose 3 aortic sites, i.e., the thoracic aorta, aortic root and aortic bifurcation, and we histologically observed and compared those sites in regard to the changes with time, the kinds of infiltrating cells and the number of inflammatory cells. We also observed the relationship between the vasa vasorum and inflammatory cell localization in the tunica media, and examined the progression of inflammation in the tunica media. Results Destruction of the vascular architecture was not seen in any of the 37 cases, but inflammatory cell infiltration was observed in 90% of the acute-phase cases. The inflammatory cell infiltration involved the tunica intima and tunica adventitia of the aorta on the 6th disease-day, and all layers of the aorta on the 13th disease-day; the infiltration peaked on the 18th disease-day. The infiltration gradually disappeared thereafter, and no significant infiltration was seen in the remote phase. The infiltrating inflammatory cells consisted mainly of CD163-positive macrophages. Comparison of the 3 sites of the aorta showed that the inflammatory cell infiltration was more severe in the aortic root and aortic bifurcation than in the thoracic aorta. The progression of inflammation to the aortic tunica media from the adventitia showed 2 patterns: 1 in which macrophages were aggregated around the vasa vasorum; and a second in which there was no such aggregation around the vasa vasorum, but there was diffuse inflammatory cell infiltration of the tunica media. In addition to this, there were findings of direct infiltration of cells from the tunica intima into the tunica media. Conclusion Inflammation in KD occurs in the aorta. The changes with time and the kinds of infiltrating cells were the same as reported to date for coronary arteries in KD. There were differences in the degree of inflammation among the 3 aortic sites. It can be thought that the inflammation from the adventitia to the media progresses via the vas vasorum, and also, there is a possibility of spreading directly. From the intima to the media, inflammation spreads directly. However, formation of aneurysms and destruction of the vascular architecture of the aorta were absent in this study, unlike in coronary arteries.