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Objective To evaluate the short-term outcomes of thoracic endovascular aortic repair (TEVAR) with outer branched and inner branched endografts in the treatment of Stanford type B aortic dissection (TBAD), and to analyze the effects of endografts on blood flow status of aortic dissection by computational fluid dynamics (CFD). Methods The clinical data of TBAD patients treated with outer branched endograft technology in outer branched endograft group and inner branched endograft technology in inner branched endograft group in Department of Vascular Surgery Tianjin Medical University General Hospital from May 2018 to December 2021 were collected, and the short-term results of two groups were analyzed retrospectively. Based on CT angiography images of patients in two groups, one typical case in each group was selected to construct personalized 3D model and CFD numerical simulation was performed. The parameters including flow field velocity distribution, wall pressure and wall shear stress (WSS) before and after surgery were compared and analyzed. Results A total of 55 cases with TBAD were enrolled, consisting of 49 cased in outer branched endograft group and 6 cases in inner branched endograft group. There was no statistical difference in baseline data between two groups, and surgical success rate were both 100%. Reconstruction of left subclavical artery(LSA) simple was 41(83.7%) cases in outer branched endograft group and all 6 cases in inner branched endograft group. In outer branched endograft group there were 5 cases with reconstruction of left common carotid artery (LCCA) combined with bridging carotic clavical artery, 2 cases with reconstruction of LCCA combined with LSA embolism, and 1 case with reconstruction of LCCA combined with LSA window. Four cases were lost during follow-up in outer branched endograft group. There were no significant differences in the aorta-related mortality rate (P=1.000), branch patency rate (P=1.000) and avoidance of secondary intervention of target vessels between the two groups during the perioperative period and follow-up period (P=0.298). After endograft implantation of two groups the flow field disturbance in dissection lesions improved significantly, aortic blood flow pattern restored normal, and local abnormally increased WSS decreased. However, the interference of inner branch on aortic arch and blood flow of branch was more obvious than that of outer branch. Conclusions Both outer branched endograft and inner branched endograft TEVAR for reconstruction of LSA had good short-term results in the treatment of TBAD. Compared with inner branched endograft, outer branched endograft has a higher anatomical fit and can restore the normal blood flow to a greater extent for aortic arch.

Introduction Atherosclerosis is a chronic inflammatory disease characterized by excessive cholesterol deposition in the walls of large and medium arteries. It is the leading cause of various cardiovascular diseases and [...], Subendothelial macrophage internalization of modified lipids and foam cell formation are hallmarks of atherosclerosis. Deubiquitinating enzymes (DUBs) are involved in various cellular activities; however, their role in foam cell formation is not fully understood. Here, using a loss-of-function lipid accumulation screening, we identified ubiquitin-specific peptidase 9 X-linked (USP9X) as a factor that suppressed lipid uptake in macrophages. We found that USP9X expression in lesional macrophages was reduced during atherosclerosis development in both humans and rodents. Atherosclerotic lesions from macrophage USP9X-deficient mice showed increased macrophage infiltration, lipid deposition, and necrotic core content than control apolipoprotein E-KO ([Apoe.sup.-/-]) mice. Additionally, loss-of- function USP9X exacerbated lipid uptake, foam cell formation, and inflammatory responses in macrophages. Mechanistically, the class A1 scavenger receptor (SR-A1) was identified as a USP9X substrate that removed the K63 polyubiquitin chain at the K27 site. Genetic or pharmacological inhibition of USP9X increased SR-A1 cell surface internalization after binding of oxidized LDL (ox-LDL). The K27R mutation of SR-A1 dramatically attenuated basal and USP9X knockdown-induced ox-LDL uptake. Moreover, blocking binding of USP9X to SR-A1 with a cell-penetrating peptide exacerbated foam cell formation and atherosclerosis. In this study, we identified macrophage USP9X as a beneficial regulator of atherosclerosis and revealed the specific mechanisms for the development of potential therapeutic strategies for atherosclerosis.

• Hyperhomocysteinemia can increase the risk of abdominal aortic aneurysm by 7-fold. • Hyperhomocysteinemia can impair aortic endothelial function via its involvement in a series of inflammatory reactions. • RASSF2 plays a role in inflammation and immune cell chemotaxis. • Homocysteine-related genes, RASSF2 and IL-1β, may participate in the formation of AAA by promoting endothelium inflammation. Abdominal aortic aneurysm (AAA) is a fatal cardiovascular disorder with high mortality and morbidity rates. To date, no drug has shown to significantly alleviate the risk of AAA. Previous studies have indicated that hyperhomocysteinemia (HHcy) significantly increases the incidence of AAA by disrupting endothelial cell homeostasis; however, the potential molecular mechanisms require clarification. Herein, we aimed to integrate transcriptomics analysis and molecular biology experiments to explore the potential molecular targets by which HHcy may increase the incidence of AAA. We integrated two AAA data profiles (GSE57691 and GSE7084) based on previously published microarray ribonucleic acid sequencing (RNAseq) data from the GEO database. Additionally, 500 μM homocysteine-treated human aorta endothelium cells microarray dataset (GSE175748) was downloaded and processed. Subsequently, single-cell RNA-seq profiles of the aortic aneurysms (GSE155468) were downloaded, scaled, and processed for further analysis. The microarray profiles analysis demonstrated that the Ras association domain family member 2 (RASSF2) and interleukin (IL)-1β are potentially the target genes involved in the HHcy-mediated aggravation of AAA formation. Single-cell RNAseq analysis revealed that RASSF2 might impair endothelial cell function by increasing inflammatory cell infiltration to participate in AAA formation. Finally, we conducted reverse transcription quantitative polymerase chain reaction and immunofluorescence analysis to validate the up-regulated mRNA expression of RASSF2 (p = 0.008) and IL-1β (p = 0.002) in AAA tissue compared to control tissue. Immunofluorescence staining revealed overexpression of RASSF2 protein in AAA tissue sections compared to control tissue (p = 0.037). Co-localization of RASSF2 and the aortic endothelium cell marker, CD31, was observed in tissue sections, indicating the potential involvement of RASSF2 in aortic endothelial cells. To summarise, our preliminary study revealed that HHcy may worsen AAA formation by up-regulating the expression of RASSF2 and IL-1β in aortic endothelium cells. [ABSTRACT FROM AUTHOR]

A reproducible canine aortic dissection (AD) model would be useful for evaluating the performance of novel endovascular treatment devices. Therefore, we attempted to create a reproducible canine model of Stanford type B AD (TBAB) by a surgical method. Computed tomography angiography was performed 2 h after the procedure to determine if a false lumen was present, and follow-up imaging was performed 10 d after the procedure using digital subtraction angiography, intravascular ultrasound (IVUS), and color Doppler flow imaging (CDFI) to confirm stable persistence of the false lumen. The success rate of model construction was 88.8% (16/18). All surviving dogs had distal re-entries (16/16). The number of re-entries in the dogs was 1.50 ± 0.52, and the mean length of the false lumen was 175.37 ± 16.98 mm. IVUS showed the area of the false lumen at the narrowest part of the arterial lumen was 84.88 ± 1.27%. The CDFI showed that the peak systolic velocity in the false lumen (10.89 ± 0.74 cm/s) was significantly slower than that in the true lumen (25.31 ± 1.72 cm/s; P<0.001). Moreover, the direction of blood flow in the true lumen was consistent, whereas that in the false lumen was disordered. We optimized the traditional surgical method to construct a canine model of TBAD to improve the success rate of model construction, and designed a novel device to lengthen the false lumen. The proposed model has wide implications in evaluating the performance of novel endovascular treatment devices and studying the AD-related hemodynamics.

A large number of epidemiological studies have confirmed that arteriosclerosis (AS) is a risk factor for abdominal aortic aneurysm (AAA). However, the relationship between AS and AAA remains controversial. The objective of this work is to better understand the association between the two diseases by identifying the co-differentially expressed genes under both pathological conditions, so as to identify potential genetic biomarkers and treatment targets for atherosclerosis-related aneurysms. Differentially-expressed genes (DEGs) shared by both AS and AAA patients were identified by bioinformatics analyses of Gene Expression Omnibus (GEO) datasets GSE100927 and GSE7084. These DEGs were then subjected to bioinformatic analyses of protein-protein interaction (PPI), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the identified hub genes were further validated by qRT-PCR in AS (n = 4), AAA (n = 4), and healthy (n = 4) individuals. Differential expression analysis revealed a total of 169 and 37 genes that had increased and decreased expression levels, respectively, in both AS and AAA patients compared with healthy controls. The construction of a PPI network and key modules resulted in the identification of five hub genes (SPI1, TYROBP, TLR2, FCER1G, and MMP9) as candidate diagnostic biomarkers and treatment targets for patients with AS-related AAA. AS and AAA are indeed correlated; SPI1, TYROBP, TLR2, FCER1G and MMP9 genes are potential new genetic biomarkers for AS-related AAA.

Earlier studies have suggested that indoleamine 2,3-dioxygenase (IDO) has a wide tissue distribution in mammals. However, detailed information on its cellular localization and also the levels of expression in various tissues is still scarce. In the present study, we sought to determine the cellular localization of IDO and also to quantify the level of its expression in various mouse tissues by using the branched DNA signal amplification assay, Western blotting, and immunohistochemical staining. The highest levels of constitutive IDO expression were found to be selectively present in the caput of epididymis, except for its initial segment. IDO expression was also detected inside the luminal compartment and even in the stereocilia within this region. In the prostate, high levels of IDO were selectively expressed in the capsular cells. In addition, high levels of IDO expression were also selectively detected in certain types of cells in the placenta, spleen, thymus, lung, and digestive tract. Notably, the morphological features of most of the positively stained cells in these organs closely resembled those of antigen-presenting cells. Based on the tissue distribution and cellular localization characteristics of IDO, it is hypothesized that its expression may serve two main functions: one is to deplete tryptophan in an enclosed microenvironment (such as in the epididymal duct lumen) to prevent bacterial or viral infection, and the other is to produce bioactive tryptophan catabolites that would serve to suppress T-cell-mediated immune responses against self-antigens, fetal antigens, or allogeneic antigens, in different situations.