Search

Purpose: Carotid artery stenting (CAS) is an option for carotid restenosis (CR) treatment with favorable outcomes. However, CAS has also emerged as an alternative to carotid endarterectomy (CEA) for the management of patients with primary carotid stenosis. This study aimed to report CR rates after CAS was performed in patients with primary lesions versus restenosis after CEA, to identify predictors of CR, and to report both neurological and overall outcomes.Materials and methods:From January 2000 to September 2018, a total of 782 patients were divided into 2 groups: The CAS (prim) group consisted of 440 patients in whom CAS was performed for primary lesions, and the CAS (res) group consisted of 342 patients with CAS due to restenosis after CEA. Indications for CAS were symptomatic stenosis/restenosis >70% and asymptomatic stenosis/restenosis >85%. A color duplex scan (CDS) of carotid arteries was performed 6 months after CAS, after 1 year, and annually afterward. Follow-up ranged from 12 to 88 months, with a mean follow-up of 34.6±18.0 months.Results:There were no differences in terms of CR rate between the patients in the CAS (prim) and CAS (res) groups (8.7% vs 7.2%, ?2=0.691, p=0.406). The overall CR rate was 7.9%, whereas significant CR (>70%) rate needing re-intervention was 5.6%, but there was no difference between patients in the CAS (prim) and CAS (res) groups (6.4% vs 4.7%, p=0.351). Six independent predictors for CR were smoking, associated previous myocardial infarction and angina pectoris, plaque morphology, spasm after CAS, the use of FilterWire or Spider Fx cerebral protection devices, and time after stenting. A carotid restenosis risk index (CRRI) was created based on these predictors and ranged from ?7 (minimal risk) to +10 (maximum risk); patients with a score >?4 were at increased risk for CR. There were no differences in terms of neurological and overall morbidity and mortality between the 2 groups.Conclusions:There was no difference in CR rate af

To remedy carotid artery stenosis and prevent stroke surgical intervention is commonly used, and the gold standard being carotid endarterectomy (CEA). During CEA cerebrovascular hemoglobin oxygen saturation decreases and when this decrease reaches critical levels it leads to cerebral hypoxia that causes neuronal damage. One of the proposed mechanism that affects changes during CEA and contribute to acute brain ischemia (ABI) is oxidative stress. The increased production of reactive oxygen species and reactive nitrogen species during ABI may cause an unregulated inflammatory response and further lead to structural and functional injury of neurons. Antioxidant activity are involved in the protection against neuronal damage after cerebral ischemia. We hypothesized that neuronal injury and poor outcomes in patients undergoing CEA may be results of oxidative stress that disturbed function of antioxidant enzymes and contributed to the DNA damage in lymphocytes. © 2019 The Authors

Hypothyroidism is a common endocrine disorder that predominantly occurs in females. It is associated with an increased risk of cardiovascular diseases (CVD), but the molecular mechanism is not known. Disturbance in lipid metabolism, the regulation of oxidative stress, and inflammation characterize the progression of subclinical hypothyroidism. The initiation and progression of endothelial dysfunction also exhibit these changes, which is the initial step in developing CVD. Animal and human studies highlight the critical role of nitric oxide (NO) as a reliable biomarker for cardiovascular risk in subclinical and clinical hypothyroidism. In this review, we summarize the recent literature findings associated with NO production by the thyroid hormones in both physiological and pathophysiological conditions. We also discuss the levothyroxine treatment effect on serum NO levels in hypothyroid patients. © 2020 The Authors

More people die from cardiovascular diseases (CVD) than from any other cause. Cardiovascular complications are thought to arise from enhanced levels of free radicals causing impaired “redox homeostasis,” which represents the interplay between oxidative stress (OS) and reductive stress (RS). In this review, we compile several experimental research findings that show sustained shifts towards OS will alter the homeostatic redox mechanism to cause cardiovascular complications, as well as findings that show a prolonged antioxidant state or RS can similarly lead to such cardiovascular complications. This experimental evidence is specifically focused on the role of glutathione, the most abundant antioxidant in the heart, in a redox homeostatic mechanism that has been shifted towards OS or RS. This may lead to impairment of cellular signaling mechanisms and elevated pools of proteotoxicity associated with cardiac dysfunction.

Chronic venous disease (CVeD) is a highly prevalent condition in the general population, and it has a significant impact on quality of life. While it is usually manifested by obvious signs, such as varicose veins and venous ulcers, other symptoms of the disease are less specific. Among the other symptoms, which include heaviness, swelling, muscle cramps and restless legs, pain is the symptom that most frequently compels CVeD patients to seek medical aid. However, there is a substantial discrepancy between pain severity and clinically detectable signs of CVeD, questioned by several opposing studies. Further evaluation is needed to clarify this subject, and to analyse whether pain development predicts objective CVeD progression. General management of CVeD starts with advising lifestyle changes, such as lowering body mass index and treating comorbidities. However, the mainstay of treatment is compression therapy, with the additional use of pharmacological substances. Venoactive drugs proved to be the drugs of choice for symptom alleviation and slowing the progression of CVeD, with micronized purified flavonoid fraction being the most effective one. Interventional therapy is reserved for advanced stages of the disease.

Abdominal Aortic Aneurysm (AAA) is a degenerative disease of the aortic wall with potentially fatal complications. Open Repair (OR) was considered the gold standard, until the emergence of Endovascular Aneurysm Repair (EVAR), which is less invasive and equally (if not more) effective. As the popularity of endovascular procedures grows, related complications become more evident, with kidney damage being one of them. Although Acute Kidney Injury (AKI) following EVAR is relatively common, its true incidence is still uncertain. Also, there is insufficient data concerning long-term renal outcomes after EVAR, especially with repeated contrast agent exposure. Despite the lack of firm evidence on the effectiveness of individual strategies, it is evident that prevention of AKI following EVAR requires a multifactorial approach. This review focuses on recent findings based on human studies regarding the current evidence of renal impairment after EVAR, its quantification and strategies for its prevention. © 2019 Bentham Science Publishers.

Sudden occlusion of an artery caused by a thrombus or emboli is the most frequent cause of acute brain ischemia (ABI). Carotid endarterectomy (CEA) represents the gold standard for preventing strokes of carotid origin. However, neuronal damage caused by ischemia and/or reperfusion may contribute to a poor clinical outcome after CEA. In response to shear stress caused by hypoxic-ischemic conditions in patients undergoing CEA, stimulation of the hypothalamic-pituitaryadrenal axis leads to biological responses known as hypermetabolic stress, characterized by hemodynamic, metabolic, inflammatory and immunological changes. These changes maintain homeostasis and assist recovery, but an unregulated inflammatory response could lead to further tissue damage and death of neurons. Nitric oxide (NO) is an important signaling molecule involved in several physiological and pathological processes, including ABI. However, an excess of NO could have detrimental effects. We hypothesized that the hypoxic-ischemic state induced by carotid clamping leads to overexpression of inducible NO synthase and that uncontrolled production of NO could adversely affect outcome after CEA. © 2018 Elsevier Ltd

Coronary artery disease (CAD) and myocardial infarction (MI) are recognized as leading causes of mortality in developed countries. Although typically associated with behavioral risk factors, such as smoking, sedentary lifestyle, and poor dietary habits, such vascular phenotypes have also long been recognized as being related to genetic background. We review the currently available data concerning genetic markers for CAD in English and non-English articles with English abstracts published between 2003 and 2018. As genetic testing is increasingly available, it may be possible to identify adequate genetic markers representing the risk profile and to use them in a clinical setting. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Background: Overexpression of inducible nitric oxide synthase (iNOS) is a key link between high-fat (HF) diet induced obesity and cardiovascular disease. Oestradiol has cardioprotective effects that may be mediated through reduction of iNOS activity/expression. Methods: In the present study, female Wistar rats were fed a standard diet or a HF diet (42% fat) for 10 weeks. iNOS gene and protein expressions were measured in heart tissue. HF-fed rats exhibited a significant increase in cardiac iNOS mRNA by 695% (p LT 0.05), iNOS protein level by 248% (p LT 0.01), without changes in nitrate/nitrite levels. Expression of CD36 protein in plasma membranes was increased by 37% (p LT 0.05), while the concentration of free fatty acids (FFA) was reduced by 25% (p LT 0.01) in HF-fed rats. Expression of the p50 subunit of nuclear factor-kappa B (NF kappa B-p50) in heart was increased by 77% (p LT 0.01) in HF-fed rats. Expression of protein kinase B (Akt) and extracellular signal-regulated kinases 1/2 (ERK1/2) were unchanged between the groups. There was a significant increase in the ratio of phospho-Akt/total Akt but not for phospho-ERK1/2/total ERK1/2 in HF-fed rats. Estrogen receptor-levels (by 50%; p LT 0.05) and serum oestradiol concentrations (by 35%; p LT 0.05) were shown to be significantly reduced in HF-fed rats. Results and Conclusion: Our results revealed that a HF diet led to increased iNOS expression, most likely via a mechanism involving Akt and NF kappa B-p50 proteins. Decreased levels of oestradiol and ER protein in the HF-fed group, in combination with increased iNOS levels are consistent with the hypothesis that oestradiol has a cardioprotective effect through its ability to regulate iNOS expression.

Copeptin is a sensitive and more stable surrogate marker for arginine vasopressin. In this study, we evaluated copeptin levels in carotid endarterectomy (CEA) patients, perioperatively, to determine whether copeptin levels can be related to carotid artery cross clamping (CC) time and to postoperative neurological outcomes. Copeptin, interleukin 6, C-reactive protein, cortisol, and brain natriuretic peptide were measured preoperatively (T1) and 3 hours postoperatively (T3) as well as intraoperatively (T2). We recruited 77 patients. Values of copeptin rose gradually over the observed times: T1 = 7.9 (6.4-9.6), T2 = 12.6 (9.3-16.8), and T3 = 72.3 (49.1-111.2) pmol/L. There was a significant difference for repeated measurement (P = .000, P = .000, and P = .000). Duration of carotid artery CC during CEA does not affect postoperative copeptin level (CC 13 minutes: 106.8 +/- 93.6 pmol/L, CC GT 13 minutes: 96.7 +/- 89.1 pmol/L; P = .634). Preoperative copeptin level was significantly higher in patients with ulcerated plaque morphology. Activation of the stress axis in patients undergoing CEA results in copeptin elevation. Duration of CC during CEA does not affect postoperative copeptin levels.

Background: The angiotensin II type 2 receptor (AT2R) - 1332 A/G polymorphism has been denoted as functional and associated with certain cardiovascular disease phenotypes. However, there are no studies considering the association of this gene polymorphism with carotid atherosclerosis (CA) and cerebrovascular events. Therefore, the aim of our study was to investigate a possible association of the AT2R - 1332 A/G polymorphism with the occurrence of carotid plaques (CPs) and history of cerebrovascular insult (CVI) in advanced CA. Methods: The study group included 381 controls and 509 patients with CA consecutively admitted for endarterectomy. Genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism method. The association was analyzed separately for males and females because the AT2R gene is located on the X chromosome. Results: The AT2R - 1332 GG genotype was associated with the advanced CA in the female study group (recessive model of inheritance, AA+AG versus GG; adjusted odds ratio [OR] = 2.25; 95% confidence interval [CI] 1.17-4.33; P=.01). In the male subgroup of patients with CA, the significant overrepresentation of G/- hemizygote was detected in patients with CVI compared to male patients without this event (crude OR = 2.05, 95% CI 1.20-3.50, P=.008). Conclusions: This study suggests a gender-specific association between the AT2R -1332 A/G polymorphism and the occurrence of CP and the history of CVI in advanced CA, but further replication studies are needed. (C) 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

An inverse association between diabetes mellitus (DM) and abdominal aortic aneurysm (AAA) risk have been reported. Apart from a lower AAA prevalence among patients with vs without DM, there are data showing that DM may exert a protective role on aneurysmal growth in patients with small AAAs, thus decreasing the risk of rupture. As atherosclerosis has almost the same risk factors as aneurysms, the decreased AAA prevalence in patients with DM may indicate that atherosclerosis is an associated feature and not a cause of the aneurysms. Alternatively, DM may be associated with factors that influence AAA formation. In this narrative review, we discuss the inverse association between DM and AAA. We also comment on underlying cellular and genetic pathophysiological mechanisms of DM, AAA and atherosclerosis. The effects of drugs, commonly prescribed in DM patients, on AAA development and growth are also considered.

The amino acid, L-Arginine (L-Arg) plays an important role in the cardiovascular system. Data from the literature show that L-Arg is the only substrate for the production of nitric oxide (NO), from which L-Arg develops its effects on the cardiovascular system. As a free radical, NO is synthesized in all mammalian cells by L-Arg with the activity of NO synthase (NOS). In states of hypertension, diabetes, hypercholesterolemia and vascular inflammation a disorder occurs in the metabolic pathway of the synthesis of NO from L-Arg which all together bring alterations of blood vessels. Experimental results obtained on animals, as well as clinical studies show that L-Arg has an effect on thrombocytes, on the process of coagulation and on the fibrolytic system. This mini review represents a summary of the latest scientific animal and human studies related to L-Arg and its mechanisms of actions with a focus on the role of L-Arg via NO pathway in cardiovascular disorders. Moreover, here we present data from recent animal and clinical studies suggesting that L-Arg could be one of the possible therapeutic molecules for improving the treatment of different cardiovascular disorders.

We report the relations between comorbidities and chronic venous disease. In this cross-sectional study, information was gathered from 1679 Serbian patients. The majority (65.0%) of patients were women. Mild forms of chronic venous disease (clinical, etiologic, anatomic and pathophysiologic [CEAP] classification; C0s-C1) were more frequent in women (11.6%), while severe forms (CEAP C4-C6) were more commonly encountered in men (42.1%). The most frequent comorbidity was emphysema/chronic obstructive pulmonary disease in both groups (74.3% in males and 70.6% in females). For females, diabetes mellitus (P LT .005), arterial hypertension (P LT .000), and skeletal/joint diseases (P LT .042) were more commonly found in the C4 to C6 category. Both males and females, with severe form of chronic venous disease, may benefit from additional screening for comorbidities. Further studies are needed to clarify the nature of association among comorbidities and chronic venous disease.

We assessed reactivity of cerebral vessels on hypercapnia in patients with carotid occlusive disease. The effects of vascular risk factors on carotid atherosclerosis and vasomotor reactivity (VMR) of cerebral arterioles were also examined. Patients (n = 50) with carotid stenosis (30% in 1 or both sides) were included; 30 patients acted as controls. Hypertension, hyperlipidemia, diabetes, cardiac diseases, inflammation, and smoking were recorded. Vasomotor reactivity was assessed with the apnea test by transcranial Doppler ultrasonography and estimated by flow velocity changes in the middle cerebral artery before and after hypercapnia induction. Vasomotor reactivity was defined by the breath holding index, and values under 0.69 were considered critical for VMR impairment. Vasomotor reactivity reduction was significant (P = .004) in patients with severe carotid stenosis ( GT 70%) and with symptomatic carotid disease (P LT .05). The risk factors did not significantly influence VMR reduction. Severe carotid stenosis impairs VMR and may increase the risk of stroke, especially in symptomatic patients.

It is now recognized that inflammatory processes regulate all stages of atherosclerosis, from disease initiation to thrombotic complications. C-reactive protein (CRP) is a plasmatic protein used as a general marker of inflammation. The high sensitivity C-reactive protein (hsCRP) refers to the measurement of CRP in blood samples using assays with sufficient sensitivity to quantify low (baseline) levels of this biomarker. Low-grade chronic inflammatory processes are linked to atherosclerosis and may be screened with the use of hsCRP, thus providing additional information in cardiovascular risk prediction. This review elaborates the role of CRP in atherogenesis and the value of hsCRP as a biomarker in cardiovascular risk prediction in both primary and secondary prevention setting.

Prema podacima Svetske zdravstvene organizacije, 15 miliona ljudi godišnje doživi moždani udar. Najčešći uzročnik moždanog udara je ishemija mozga, koja se dešava u skoro 85% slučajeva. Moždana ishemija izazvana tromboembolijskim događajima definiše se kao trajno ili prolazno smanjenje cirkulacije krvi, što za posledicu ima nedostatak kiseonika, glukoze i ostalih važnih nutritijenata, dovodeći postepeno do metaboličkih promena i apoptoze ćelija. Tokom operativnih zahvata kao što je karotidna endarterektomija (CEA) može doći do hipoksično-ishemičnog stanja mozga ili akutne ishemije mozga (ABI), kao i do samog moždanog udara. Glavni uzrok ABI u toku CEA je cerebralna hipoperfuzija koja je uzrokovana klemovanjem karotidne arterije, pri čemu dolazi do hipoksije, što može predstavljati jedan od okidača za niz fizioloških odgovora organizma, među kojima je oslobađanje različitih medijatora inflamacije. Jedan od medijatora inflamacije je i azot monoksid (NO), slobodni radikal koji pored mnogobrojnih fizioloških efekata ima važnu ulogu i u samom imunom odgovoru organizma. Međutim, NO može biti veoma štetan i svojim delovanjem dovesti do oštećenja ćelija i tkiva. Nedostatak podataka u literaturi o ulozi endotelne NOS (eNOS) i inducibilne NOS (iNOS) tokom CEA, kao i mehanizama njihove regulacije u stanjima ishemije, ukazuju na pravac kojim treba da se usmere buduća istraživanja. Poznavanje molekularnih mehanizama regulacije aktivnosti i ekspresije iNOS, svakako će pomoći razvoju novih terapijskih strategija u tretmanu štetnih efekata produkcije slobodnih radikala, pre svega nekontrolisane produkcije NO., According to the World Health Organization, 15 million people per year are affected by stroke. The most common cause of stroke is brain ischemia, which occurs in almost 85% of cases. Ischemia caused by thromboembolism is defined as permanently or temporarily decreased blood flow which prevents an adequate delivery of oxygen, glucose and other important nutrients, leading progressively to metabolic changes and cell apoptosis. Carotid endarterectomy (CEA) can cause hypoxic - ischemic states of the brain or acute brain ischemia (ABI) leading eventually to stroke. The main cause of ABI as a result of CEA is cerebral hypoperfusion caused by clamping of carotid arteries, when hypoxia occurs.. Hypoxia per se is one of the triggers of complex physiological responses in the body, including the release of various mediators of inflammation. One of these inflammatory mediators is nitric oxide (NO), a free radical which has numerous physiological effects and also plays an important role in the immune response of the organism. However, NO may be very harmful and cause cell and tissue damage. The lack of literature data on the role of endothelial NOS (eNOS) and inducible NOS (iNOS) during CEA, as well as the mechanisms of their regulation in ischemic conditions, suggest that intensifying future research in this field is very important. An insight into molecular mechanisms of iNOS activity and expression regulation will certainly help to develop new therapeutic strategies for treating harmful effects of free radicals, especially uncontrolled production of NO.

We evaluated the prognostic value of copeptin levels in a cohort of surgical patients after elective carotid endarterectomy (CEA). Twenty-one patients with perioperative stroke were prospectively recruited. The diagnosis of cerebrovascular event (CVE) was confirmed by computed tomography. Additionally, 21 patients with CEA without any complications (control patients) were enrolled. Blood samples were taken within 3 hours of the symptom onset. Circulating copeptin level was significantly higher in patients with CVE when compared to controls (P = .025), and significantly higher in nonsurvivors than in survivors (P = .030) after CVE. Plasma concentrations of interleukin 6 (IL-6) and C-reactive protein (CRP) were also elevated in patients with CVE (IL-6: P = .043; CRP: P = .002). We conclude that the activation of the stress axis in patients with CEA results with copeptin elevation, but more so in patients with perioperative stroke. Copeptin may be a helpful biomarker for stroke risk assessment in patients after CEA.

BACKGROUND: To present outcomes following an operative approach of extracranial carotid artery aneurysm (ECAAs) based on anatomic types and associated kinks. METHODS: This study represents retrospective analysis of anatomic type based approach to operative repair of 84 patients with ECAA from 1994 to 2011, 28 (33.3%) with associated kinking. Patients were followed for neurological ischemic events, hematoma, cranial nerve injury, myocardial infarction, neurological, and overall mortality. The results are presented as early, within 30 days after the surgery, and long term during the follow-up. RESULTS: In the early postoperative period, there were no strokes or mortalities, cranial nerve injury rate was 2.4% while 1 patient had myocardial infarction (1.2%). During the follow-up, 4 patients (4.8%) had stroke, out of which 2 patients died (2.3%), while overall mortality was 4.6%. The average 5-year survival rate was 96 +/- 3%. CONCLUSION: Excellent outcomes can be obtained with surgical repair of ECAA, which should be tailored to the anatomic types and presence of kinks. (C) 2014 Elsevier Inc. All rights reserved.

Acute brain ischemia caused by transient ischemic attack initiates a complex sequence of events in the central nervous system and hypothalamic-pituitary-adrenal (HPA) axis which may ultimately culminate in neuronal and cell damage. The brain is highly susceptible to ischemia and in response to stress shows changes in morphology and chemistry that are largely reversible. These responses are known to modify the function of the HPA axis, but their mechanisms are not yet clear. Duration and size of the HPA axis activation are regulated by corticotropin-releasing hormone, vasopressin (AVP), and glucocorticoids, including cortisol. Numerous studies suggest that activation of these hormones following brain ischemia can result in neurohormonal dysfunction that can exacerbate long-term prognosis following stroke. These studies represent evidence that changes in the HPA axis play an important role in brain ischemia.

Cardiovascular disease (CVD) is common cause of death in humans and its major underlying pathology is atherosclerosis. Atherosclerosis is a chronic inflammatory disease that predisposes to coronary artery disease (CAD), stroke and peripheral arterial disease, responsible for most of the cardiovascular morbidity and mortality. This inflammatory process, triggered by the presence of lipids in the vascular wall, and encompasses a complex interaction among inflammatory cells, vascular elements, and lipoproteins through the expression of several adhesion molecules and cytokines. Obesity is a risk factor for CVD but this association is not fully understood. Altered levels of obesity related peptides such as ghrelin may play an important role in this pathophysiology. Recent evidence indicates that ghrelin features several cardiovascular activities, including increased myocardial contractility, vasodilatation and protection from myocardial infarction. Recent data demonstrate that ghrelin can influence important key events in atherogenesis and thus they may play a role in atherosclerosis. In this review we present the latest data from recent animal and clinical studies which focus on a novel approach to ghrelin as a potential therapeutic agent in the treatment of a complex disease like atherosclerosis. Thus, ghrelin may become a new therapeutic target for the treatment of CVD. Further studies are necessary to investigate the potential mechanisms involved in the effects of ghrelin on the cardiovascular system.

Atherosclerosis is known as an inflammatory disease in which a recruitment of leukocytes to the endothelium wall represents a preliminary step of the initiation and the development of disease. The P-selectin glycoprotein ligand (PSGL-1) seems to be the major molecule mediating leukocyte-endothelium interactions and leukocyte rolling on stimulated endothelium. There are limited number of studies reporting on association of Met62Ile SNP in PSGL-1 gene and the risk for atherosclerosis. The aim of this study was to analyze possible association of this polymorphism with an advanced carotid atherosclerosis and biochemical markers of inflammation and haemostasis. The 275 patients consecutively admitted for carotid endarterectomy with stenosis GT 70% and 256 controls of the same ethnic origin were included in the study. The Met62Ile genotypes were determined by PCR RFLP. The Ile/Ile homozygotes had significantly higher CRP compared to the other genotypes in patients. Female patients had Ile allele dose-dependent association with the carotid plaque presence (Met/Met vs. Met/Ile vs. Ile/Ile; OR 1, OR 2.02, CI 1.0-4.08, OR 4.08, CI 1.0-16.81, respectively, p = 0.04). Our results suggest the impact of PSGL-1 Met62Ile polymorphism on inflammation in advanced atherosclerosis. We observed the sex-differential association of Met62Ile with advanced carotid atherosclerosis. Studies in larger and different populations should validate and further examine the suggested role of genetic variations in PSGL-1 with atherosclerosis and thrombosis.

Introduction: The ACE I/D polymorphism was mostly investigated in association with intima-media thickness, rarely with severe atherosclerotic phenotype. Materials and methods: We investigated the association of I/D polymorphism with severe carotid atherosclerosis (CA) (stenosis GT 70%) in asymptomatic and symptomatic patients undergoing carotid endarterectomy. The 504 patients subjected to endarterectomy and 492 healthy controls from a population in Serbia were investigated as a case-control study. Results: The univariate logistic regression analysis revealed ACE DD as a significant risk factor for severe CA (odds ratio [OR] = 1.3, 95% confidence interval [CI] 1.0-1.7, p = 0.04). After adjustment for the common risk factors (age, hypertension, smoking, and HDL) ACE was no longer significant. However, we found a significant independent influence of DD genotype on plaque presence in a normotensive subgroup of patients (OR 1.8, CI 1.2-3.0, p = 0.01, corrected for multiple testing). In symptomatic patients D allele carriers were significantly more frequent compared with asymptomatic patients (OR 1.6 CI 1.0-2.6, p = 0.05). Conclusions: Our data suggests that ACE I/D is not an independent risk factor for severe CA. On the other hand, a significant independent genetic influence of ACE I/D appeared in normotensive and symptomatic patients with severe CA. This should be considered in further research toward resolving the complex genetic background of severe CA phenotype.

Objective: Matrix metalloproteinases (MMPs) are involved in the remodeling of the extracellular matrix in the arterial wall. Collagen I is associated with vascular smooth muscle cell (VSMC) migration and monocyte differentiation. MMP-8 is expressed in atherosclerotic plaque and preferentially cleaves collagen type I. The aim of this study was to investigate the associations of two MMP-8 promoter polymorphisms, rs11225395 (-799 C/T) and rs1320632 (-381 A/G), with carotid plaque occurrence, and the influence of these polymorphisms on MMP-8 mRNA expression in plaque tissue. Methods: The study included a total of 766 participants: 277 controls and 489 patients with carotid atherosclerosis undergoing endarterectomy. The two investigated polymorphisms were genotyped by PCR-RFLP. The gene expression analysis was performed by real-time PCR. Results: In females only, a significantly higher frequency of the -381G allele was found in patients with carotid atherosclerosis compared to controls (OR, 1.7; 95% CI 1.1-2.9; p = 0.001). Significant up-regulation of MMP-8 gene expression was observed in patients carrying the -381G allele compared to those with the AA genotype (mean factor, 3.54; SE. range, 0.643-19.551; p = 0.007). Carotid plaque tissue of the haplotype G(-381)T(-799) showed a significantly higher mRNA level compared with the reference A(-381)C(-799) haplotype (p = 0.003). Conclusion: Our preliminary results indicate that MMP-8 -381A/G and -799 C/T gene polymorphisms could be risk factors for carotid atherosclerosis. Further validation and functional studies are needed to establish the potential regulatory role of these polymorphisms and their impact on susceptibility to carotid atherosclerosis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

In this study we compared the effects of duration of cold ischemia (longer and shorter ischemia) on the yield, viability and preservation of the physiological function and insulin secretion of adult human pancreatic islets in short-term (seven days) culture. Based on the tested parameters, we established that there are no major differences between these two test groups and that the storage and transport of pancreatic tissue in physiological solution at 4 degrees C gives quite satisfactory results.

The role of inflammation is well established in the pathogenesis of atherosclerosis and an increased level of circulating inflammatory markers may predict the future risk of atherosclerosis progression and plaque rupture. C-reactive protein (CRP) identification by hypersensitive methods (high-sensitivity CRP [hsCRP]) has become a clinical and laboratory inflammation marker. Carotid endarterectomy (CEA) is a well-established procedure for carotid stenosis treatment which can reduce stroke rate. Internal carotid artery (ICA) restenosis reduction may be prevented by the anti-inflammatory effect of statins. This review considers the recent findings on the presence of hsCRP and C3 complement concentration and inflammatory plaque composition as well as their effects on ICA restenosis rate, following eversion CEA with emphasis on human studies.

Ateroskleroza se manifestuje kao bolest koronarnih, perifernih i cerebrovaskularnih arterija. Aterosklerotične promene dovode do sužavanja prečnika arterija što dovodi do ishemije u mnogobrojnim organima, čime je poremećeno normalno funkcionisanje kako organa tako i organizma u celini. Centralnu ulogu u patogenezi ateroskleroze zauzima aterogena dislipidemija. Razvoj ateroskleroze počinje malim oštećenjima endotela izazvanim različitim činiocima, koji mogu uticati na povećanje ekspresije adhezivnih molekula. Disfunkcionalni endotel je mesto gde dolazi do infiltracije i akumulacije lipoproteina male gustine (LDL) u vaskularnom zidu. LDL tada podleže oksidativnoj modifikaciji, a kao krajnji produkt nastaje oksidovani LDL (oxLDL). Mnogobrojna eksperimentalna istraživanja ukazuju da su male guste LDL-čestice mnogo aterogenije u poređenju sa većim i lakšim LDL česticama. LDL podleže različitom stepenu oksidacije. Minimalno oksidovani LDL (LDL( - )) pokazuje svoj aterogeni potencijal time što stimuliše vaskularne endotelne ćelije na lučenje velikog broja proinflamatornih molekula kao što su adhezivni molekuli, hemotaktni proteini i faktori rasta. Za razliku od LDL(-), potpuno oksidovani LDL nema sposobnost preuzimanja putem LDL receptora već ga prepoznaju recptori 'hvatači', što dovodi do formiranja makrofag penastih ćelija a u nastavku i stvaranja ateroma. Prisustvo oxLDL u cirkulaciji kod ljudi predstavlja jedan od glavnih faktora rizika od kardiovaskularnih bolesti i ateroskleroze. Buduće studije imaju zadatak da izuče šta se dešava sa oxLDL- om in vivo, kao i da li je i u kojoj meri oksidacija LDL koja igra ključnu ulogu u nastanku penastih ćelija, značajna u kasnijim fazama stvaranja plaka.U okviru ovog preglednog člana, izloženi su najnoviji podaci iz litearture o uticaju oxLDL-a u patogenezi arteroskleroze., Atherosclerosis is manifested as a disease of coronary, cerebrovascular and peripheral arteries. Atherosclerotic changes lead to narrowing of the diameter of the arteries leading to ischemia in various organs, which disturbes the normal functioning of both organs and organism as a whole. Atherogenic dyslipidemia has a central role in the pathogenesis of atherosclerosis. Development of atherosclerosis begins with endothelial damage caused by variety of factors, which may cause an increase in expression of adhesion molecules. Dysfunctional endothelium is the place where infiltration and accumulation of low density lipoprotein (LDL) in the vascular wall occurs. LDL undergoes oxidative modification and the final product produced is oxidized LDL (oxLDL). Numerous experimental studies sug- gest that small dense LDL particles are particularly atherogenic compared with larger and lighter LDL particles. LDL is subject to varying degrees of oxidation. Minimally oxidized LDL (LDL(- )) exhibits its atherogenic potential by stimulating vascular endothelial cells to secrete a large number of proinflammatory molecules, such as adhesion molecules, chemotactic proteins, and growth factors. Unlike the LDL(-), fully oxidized LDL cannot bind the LDL receptors, but is recognized by scavenger receptors, which leads to the formation of macrophage foam cells and eventually atheroma. The presence of oxLDL in the circulation in humans is a major risk factor for cardiovascular disease and atherosclerosis. Future studies are warranted to elucidate the role of oxLDL in vivo, and whether and to what extent oxidation of LDL, which plays a key role in the development of foam cells, is critical for later stages in creating the plaque. In this review article, we present current knowledge of the impact of oxLDL in the pathogenesis of arteriosclerosis.

Objectives: Stromelysin-1 (MMP-3) as a key member of metalloproteinase family could have an important role in atherogenesis. The 5A/6A polymorphism in the promoter of MMP-3 gene affects the level of MMP-3 gene expression. We assessed whether the MMP-3 promoter low-and high-activity genotypes are related to susceptibility for carotid atherosclerosis (CA) in Serbian population. Design and methods: The study group of case-control design consisted of 515 participants. The 265 patients with ultrasonographic evidence of carotid plaque presence were recruited for the study. The 5A/6A polymorphism was typed by RFLP-PCR. Results: There was significantly higher prevalence of genotypes containing 6A allele in the patients with CA compared to controls (p LT 0.05). The model of inheritance with the dominant effect of 6A allele gave elevated and significant OR for carotid atherosclerosis (adjusted OR 2.35, CI = 1.0-5.5, p=0.048). Conclusions: Subjects carrying genotypes with 6A allele had significantly higher susceptibility to carotid atherosclerosis. (C) 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.