Irisin reduces ischemia-induced neuronal injury via activation of the Akt and ERK1/2 signaling pathways and contributes to the neuroprotective effect of physical exercise against cerebral ischemia, suggesting that irisin may be a factor linking metabolism and cardio-cerebrovascular diseases.

The mismatch between the distal diameter of the stent graft and the diameter of the compressed true lumen seems to be the major factor in the occurrence of SIDR. Placement of an RBS, as an adjunctive technique to TEVAR, could reduce the incidence of SIDR. On the basis of early- to midterm observations, RBSs may improve morphological remodeling of the dissected aorta at certain levels.

Neointimal hyperplasia as a consequence of vascular injury is aggravated by inflammatory reaction and oxidative stress. The α7 nicotinic acetylcholine receptor (α7nAChR) is a orchestrator of cholinergic anti-inflammatory pathway (CAP), which refers to a physiological neuro-immune mechanism that restricts inflammation. Here, we investigated the potential role of CAP in neointimal hyperplasia using α7nAChR knockout (KO) mice. Male α7nAChR-KO mice and their wild-type control mice (WT) were subjected to wire injury in left common carotid artery. At 4 weeks post injury, the injured aortae were isolated for examination. The neointimal hyperplasia after wire injury was significantly aggravated in α7nAChR-KO mice compared with WT mice. The α7nAChR-KO mice had increased collagen contents and vascular smooth muscle cells (VSMCs) amount. Moreover, the inflammation was significantly enhanced in the neointima of α7nAChR-KO mice relative to WT mice, evidenced by the increased expression of tumor necrosis factor-α/interleukin-1β, and macrophage infiltration. Meanwhile, the chemokines chemokine (C-C motif) ligand 2 and chemokine (CXC motif) ligand 2 expression was also augmented in the neointima of α7nAChR-KO mice compared with WT mice. Additionally, the depletion of superoxide dismutase (SOD) and reduced glutathione (GSH), and the upregulation of 3-nitrotyrosine, malondialdehyde and myeloperoxidase were more pronounced in neointima of α7nAChR-KO mice compared with WT mice. Accordingly, the protein expression of NADPH oxidase 1 (Nox1), Nox2 and Nox4, was also higher in neointima of α7nAChR-KO mice compared with WT mice. Finally, pharmacologically activation of CAP with a selective α7nAChR agonist PNU-282987, significantly reduced neointima formation, arterial inflammation and oxidative stress after vascular injury in C57BL/6 mice. In conclusion, our results demonstrate that α7nAChR-mediated CAP is a neuro-physiological mechanism that inhibits neointima formation after vascular injury via suppressing arterial inflammation and oxidative stress. Further, these results imply that targeting α7nAChR may be a promising interventional strategy for in-stent stenosis.

Objective: We have summarized the incidence, anticoagulation panels, laboratory characteristics, and mortality of venous thromboembolism (VTE) in hospitalized patients with coronavirus disease 2019 .Methods: After systematically searching PubMed, Embase, the Cochrane Library, MedRxiv, and BioRxiv, a systematic review and meta-analysis of 18 retrospective, 6 prospective observational, and 2 cross-sectional studies was performed according to the guidelines of the PRISMA (preferred reporting items for systematic reviews and meta-analyses) statement.Results: Overall, 4382 hospitalized patients with COVID-19 were included. Men accounted for significantly more patients than did women (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.25-2.02; P < .001). The total incidence of VTE among the patients with COVID-19 was 28.3% (95% CI, 21.6%-35.4%), with an incidence of 38.0% (95% CI, 29.1%-47.4%) and 17.2% (95% CI, 11.4%-23.8%) among those with severe and general COVID-19, respectively. The total incidence of deep vein thrombosis (DVT) of the lower extremities was 18.3% (95% CI, 10.8%-27.2%). The incidence of DVT was 22.1% (95% CI, 11.0%-35.5%) and 12.8% (95% CI, 5.0%-23.3%) in those with severe and general COVID-19, respectively. The total incidence of pulmonary embolism was 17.6% (95% CI, 12.3%-23.5%), with a rate of 21.7% (95% CI, 14.8%-29.3%) in severe cases and 12.5% (95% CI, 6.1%-23.5%) in general cases. When COVID-19 severity was unclassified, the mortality for the patients with VTE was not significantly greater (25.2%; 95% CI, 12.2%-40.5%) than that for those without VTE (10.2%; 95% CI, 3.4%-19.5%; OR, 1.88; 95% CI, 0.46-7.64; P ¼ .377). However, among the patients with severe COVID-19, those who had developed VTE had significantly greater mortality compared with those without VTE (OR, 2.02; 95% CI, 1.15-3.53; P ¼ .014). The patients with COVID-19 and VTE had significantly higher D-dimer levels than did similar patients without VTE in multiple studies. Conclusions:The occurrence of VTE, DVT, and pulmonary embolism has been substantial among hospitalized patients with COVID-19, especially among those with severe COVID-19. Patients with severe COVID-19 and VTE had significantly greater mortality compared with similar patients without VTE. An increased D-dimer level might be an indicator of the occurrence of VTE in patients with COVID-19.

JMJD3 is a novel factor involved in vascular remodelling. Deficiency of JMJD3 reduces neointima formation after vascular injury by a mechanism that inhibits Nox4-autophagy signalling activation, and suggesting JMJD3 may serve as a perspective target for the prevention and treatment of vascular diseases.

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Background: The transcription factor BACH1 (BTB and CNC homology 1) suppressed endothelial cells (ECs) proliferation and migration and impaired angiogenesis in the ischemic hindlimbs of adult mice. However, the role and underlying mechanisms of BACH1 in atherosclerosis remain unclear. Methods: Mouse models of atherosclerosis in endothelial cell (EC)-specific-Bach1 knockout mice were used to study the role of BACH1 in the regulation of atherogenesis and the underlying mechanisms. Results: Genetic analyses revealed that coronary artery disease-associated risk variant rs2832227 was associated with BACH1 gene expression in carotid plaques from patients. BACH1 was upregulated in ECs of human and mouse atherosclerotic plaques. Endothelial Bach1 deficiency decreased turbulent blood flow- or western diet-induced atherosclerotic lesions, macrophage content in plaques, expression of endothelial adhesion molecules (ICAM1 [intercellular cell adhesion molecule-1] and VCAM1 [vascular cell adhesion molecule-1]), and reduced plasma TNF-α (tumor necrosis factor-α) and IL-1β levels in atherosclerotic mice. BACH1 deletion or knockdown inhibited monocyte–endothelial adhesion and reduced oscillatory shear stress or TNF-α-mediated induction of endothelial adhesion molecules and/or proinflammatory cytokines in mouse ECs, human umbilical vein ECs, and human aortic ECs. Mechanistic studies showed that upon oscillatory shear stress or TNF-α stimulation, BACH1 and YAP (yes-associated protein) were induced and translocated into the nucleus in ECs. BACH1 upregulated YAP expression by binding to the YAP promoter. BACH1 formed a complex with YAP inducing the transcription of adhesion molecules. YAP overexpression in ECs counteracted the antiatherosclerotic effect mediated by Bach1-deletion in mice. Rosuvastatin inhibited BACH1 expression by upregulating microRNA let-7a in ECs, and decreased Bach1 expression in the vascular endothelium of hyperlipidemic mice. BACH1 was colocalized with YAP, and the expression of BACH1 was positively correlated with YAP and proinflammatory genes, as well as adhesion molecules in human atherosclerotic plaques. Conclusions: These data identify BACH1 as a mechanosensor of hemodynamic stress and reveal that the BACH1-YAP transcriptional network is essential to vascular inflammation and atherogenesis. BACH1 shows potential as a novel therapeutic target in atherosclerosis.

Rationale: Sorting Nexin 10 (SNX10) has been reported to play a critical role in regulating macrophage function and lipid metabolism. Objective: To investigate the precise role of SNX10 in atherosclerotic diseases and the underlying mechanisms. Methods and Results: SNX10 expression was compared between human healthy vessels and carotid atherosclerotic plaques. Myeloid cell-specific SNX10 knockdown mice were crossed onto the APOE-/- background and atherogenesis (high cholesterol diet-induced) was monitored for 16 weeks. We found that SNX10 expression was increased in atherosclerotic lesions of aortic specimens from humans and APOE-/- mice. Myeloid cell-specific SNX10 deficiency (ΔKO) attenuated atherosclerosis progression in APOE-/- mice. The population of anti-inflammatory monocytes/macrophages was increased in the peripheral blood and atherosclerotic lesions of ΔKO mice. In vitro experiments showed that SNX10 deficiency inhibited foam cell formation through interrupting the internalization of CD36, which requires the interaction of SNX10 and Lyn-AKT. The reduced Lyn-AKT activation by SNX10 deficiency promoted the nuclear translocation of TFEB, thereby enhanced lysosomal biogenesis and LAL activity, resulting in an increase of free fatty acids to fuel mitochondrial fatty acid oxidation. This further promoted the reprogramming of macrophages and shifted toward the anti-inflammatory phenotype. Conclusions: Our data demonstrate for the first time that SNX10 plays a crucial role in diet-induced atherogenesis via the previously unknown link between the Lyn-Akt-TFEB signaling pathway and macrophage reprogramming, suggest that SNX10 may be a potentially promising therapeutic target for atherosclerosis treatment.