Objectives Arterial wall inflammation and remodelling are the characteristic features of Takayasu’s arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. Studies have shown that cellular senescence in tissue is closely related to local inflammation persistence. We aimed to investigate whether VSMCs senescence contributes to vascular inflammation and the prosenescent factors in TAK. Methods VSMCs senescence and senescence-associated secretory phenotype were detected by histological examination, bulk RNA-Seq and single-cell RNA-seq conducted on vascular surgery samples of TAK patients. The key prosenescent factors and the downstream signalling pathway were investigated in a series of in vitro and ex vivo experiments. Results Histological findings, primary cell culture and transcriptomic analyses demonstrated that VSMCs of TAK patients had the features of premature senescence and contributed substantially to vascular inflammation by upregulating the expression of senescence-associated inflammatory cytokines. IL-6 was found to be the critical cytokine that drove VSMCs senescence and senescence-associated mitochondrial dysfunction in TAK. Mechanistically, IL-6-induced non-canonical mitochondrial localisation of phosphorylated STAT3 (Tyr705) prevented mitofusin 2 (MFN2) from proteasomal degradation, and subsequently promoted senescence-associated mitochondrial dysfunction and VSMCs senescence. Mitochondrial STAT3 or MFN2 inhibition ameliorated VSMCs senescence in ex vivo cultured arteries of TAK patients. Conclusions VSMCs present features of cellular senescence and are actively involved in vascular inflammation in TAK. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence.

BACKGROUND:We discuss the presentation and management of extracranial carotid artery aneurysms (ECAAs) and to develop a new type of classification. MATERIAL AND METHODS:A retrospective review of 35 ECAAs patients who were admitted in our institution ...

Background: Varicose veins are found to be associated with increased risk of venous thromboembolism (VTE) in many observational studies, but whether varicose veins are causally associated with VTE remains unclear. Therefore, we used a series of Mendelian randomization (MR) methods to investigate that association.Methods: 23 independent single-nucleotide polymorphisms (SNPs) for varicose veins were obtained from the Pan UK Biobank analysis. The outcomes datasets for deep vein thrombosis (DVT), pulmonary embolism (PE) and venous thromboembolism (VTE) were obtained from the FinnGen study. Before analysis, body mass index (BMI) and height were included as confounders in our MR model. Basic MR [inverse-variance weighted (IVW), weight-median, penalized weighted-median and MR-Egger methods] and MR-PRESSO were performed against each outcome using the whole SNPs and SNPs after excluding those associated with confounders. If causal associations were suggested for any outcome, a basic MR validation analysis, a multivariable MR analysis with BMI and height, a Causal Analysis Using Summary Effect estimates (CAUSE), and a two-step MR analysis with BMI and height, would follow.Results: Using 21 qualified SNPs, the IVW method (OR: 1.173, 95% CI: 1.070–1.286, p < 0.001, FDR = 0.002), the weighted median method (OR: 1.255, 95% CI: 1.106–1.423, p < 0.001, FDR = 0.001), the penalized weighted median method (OR: 1.299, 95% CI: 1.128–1.495, p < 0.001, FDR = 0.001) and the MR-PRESSO (OR: 1.165, 95% CI: 1.067–1.273, p = 0.003, FDR = 0.009) suggested potential causal effect of varicose veins on DVT, but no cause effect was found for PE and VTE. Excluding SNPs associated with confounders yielded similar results. The causal association with DVT was validated using a self-reported DVT cohort (IVW, OR: 1.107, 95% CI: 1.041–1.178, p = 0.001). The causal association maintained after adjustment for height (OR = 1.105, 95% CI: 1.028–1.188, p = 0.007), BMI (OR = 1.148, 95% CI: 1.059–1.244, p < 0.001) and them both (OR = 1.104, 95% CI: 1.035–1.177, p = 0.003). The causal association also survived the strict CAUSE (p = 0.018). Finally, in two-step MR, height and BMI were found to have causal effects on both varicose veins and DVT.Conclusion: Genetically predicted varicose veins may have a causal effect on DVT and may be one of the mediators of obesity and taller height that predispose to DVT.

To provide a meta-analysis of studies evaluating long-term all-cause mortality, aneurysm-related mortality and re-intervention after open or endovascular repair for abdominal aortic aneurysm. Electronic bibliographic sources were interrogated using a combination of free text and controlled vocabulary searches to identify studies comparing the long-term outcomes of open and endovascular repair for abdominal aortic aneurysm. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. Fixed effect or random effects models were used. We retrieved 4 randomized controlled trials (RCTs; 2,783 patients), 7 nonrandomized trials (86,035 patients). The primary outcome was all-cause mortality. Heterogeneity was high and publication bias could not be excluded. Despite these limitations, the analysis showed that open and endovascular abdominal aortic aneurysm repair had similar all-cause mortality (OR 1.16, 95% CI, 0.89-1.51) over 5 years follow up, which was maintained after at least 10 years of follow-up (OR 0.87, 95% CI, 0.73-1.03). There was no significant difference in aneurysm-related mortality by 5 years or longer follow-up. A significantly lower proportion of patients undergoing open repair required reintervention (OR 0.38, 95% CI 0.24-0.64), which was maintained over 5 years of follow-up. There is no long-term survival difference between the patients who underwent open or endovascular aneurysm repair. There is significantly higher risk of reinterventions after endovascular aneurysm repair.

Peripheral vascular disease (PVD) is a common clinical manifestation of atherosclerosis. Vascular endothelial growth factor (VEGF) gene therapy is a promising approach for PVD treatment. However, due to single-gene therapy limitations and high H₂O₂ pathological microenvironment, VEGF gene therapy are not as expectations and its clinical application are limited. Synergistic effects of Nerve factors and vascular factors in angiogenesis have attracted attention in recent years. In this study, VEGF and nerve growth factor (NGF) genes co-delivery nanoparticles (VEGF/NGF-NPs) were prepared by using H₂O₂ responsive 6s-PLGA-Po-PEG as a carrier. 6s-PLGA-Po-PEG could react with H₂O₂ specifically due to the internal peroxalate bond. Angiogenic effects of VEGF/NGF-NPs has been evaluated in cells and hindlimb ischemia mice model. Results showed that VEGF/NGF-NPs promoted VEGF and NGF co-expression simultaneously, eliminated excessive H₂O₂, strengthened reactions between SH-SY5Ys and HUVECs, and finally enhanced migration, tube formation, proliferation and H₂O₂ damage resistance of HUVECs. VEGF/NGF-NPs also recovered blood perfusion, promoted the expression of VEGF, NGF, eNOS and NO, and enhanced vascular coverage of pericytes. Treatment effects of VEGF/NGF-NPs may related to VEGF/eNOS/NO pathway. Altogether, VEGF/NGF-NPs eliminated excessive H₂O₂ while achieving gene co-delivery, and promoted stable angiogenesis. It’s a promising way for PVD treatment by using VEGF/NGF-NPs. Graphical Abstract