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Atherosclerosis (AS) is a common disease that seriously threatens human health. So far, the pathogenesis of AS has not been fully understood. This project investigates the effects of circARHGAP12 on AS and its regulatory mechanism. ApoE−/− knockout mice (ApoE) were adopted and reared with a high‐fat diet to construct an AS model. Lentivirus was established to knock down the expression of circARHGAP12 in mice. After 12 weeks, the aorta was removed and the expression of circARHGAP12 was detected. Vascular oil red O staining was used to detect the degree of AS. The expression of inflammatory factors was detected by ELISA. Aortic smooth muscle cells (MASMCs) were cultured to evaluate the effects of circARHGAP12 on the phenotype of MASMCs. RNA pull‐down and luciferase assay were used to verify the downstream target genes of circARHGAP12. In addition, the effects of circARHGAP12 on MASMCs proliferation and migration were detected by MTT and transwell assay. Compared with the normal group, the expression of circARHGAP12 in the MASMCs under ox‐LDL treatment was elevated, and circARHGAP12 silencing could inhibit AS in vitro and in vivo. The results of the mechanism study showed that circARHGAP12 can directly bind with miR‐630. In addition, miR‐630 can also target EZH2 to modulate the transcription of TIMP2 and to influence the migration of MASMCs. circARHGAP12 is upregulated in AS. CircARHGAP12 knockdown can inhibit the progression of AS. This study expands on the role of circRNA in AS and provides potential targets for the treatment of AS. [ABSTRACT FROM AUTHOR]

Background: Angiotensin-converting enzyme (ACE) I/D polymorphism has been indicated to be correlated with aortic aneurysm (AA) susceptibility, but study results are still debatable. Thus, a meta-analysis was conducted.Methods: Databases including PubMed, Embase, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) were searched. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.Results: Ten studies with 3557 cases and 5231 controls were included in this meta-analysis. The association between ACE I/D genotype and AA risk was significant (OR=1.30; 95%CI, 1.07-1.57; p<0.01; I(2)=68%). When stratified by ethnicity, a significantly elevated risk was observed in Caucasians (OR=1.31; 95%CI, 1.07-1.61; p<0.01; I(2)=71%). In the abdominal AA subgroup, a significantly increased risk was observed (OR=1.29; 95%CI, 1.03-1.62; p=0.02; I(2)=73%). However, ACE I/D polymorphism was not associated with thoracic AA risk (OR=1.33; 95%CI, 0.85-2.07; p=0.21; I(2)=52%). Subgroup analysis on blood pressure status showed that an increased risk was found in hypertensive patients (OR=1.52; 95%CI, 1.02-2.26; p=0.04; I(2)=0%) but not in normotensive subjects (OR=1.46; 95%CI, 0.72-2.96; p=0.30; I(2)=25%).Conclusions: In conclusion, this meta-analysis suggested that ACE I/D polymorphism is a risk factor for AA. [ABSTRACT FROM AUTHOR]

Integrin (ITG) α5β1 is a dominant fibronectin receptor that is abundantly expressed on the surface of vascular smooth muscle cells (VSMCs). However, the association between integrin α5β1 and the proliferation and migration of VSMCs has yet to be elucidated. The aim of the present study was to characterize the roles of ITGα5 and ITGβ1 in the proliferation and migration of VSMCs, and to determine the effects of ITGα5β1 on integrin-linked kinase (ILK) and focal adhesion kinase (FAK) mRNA expression. Lentiviral expression vectors as well as RNA interference vectors of ITGα5 and ITGβ1 were successfully constructed and transfected into VSMCs to obtain ITGα5‑ and ITGβ1‑overexpressing or -silenced cells, respectively. Cell cycle distribution, proliferation and migration were analyzed in the transfected VSMCs in order to clarify the roles of ITGβ1 and ITGα5 in the proliferation and migration of VSMCs. ITGβ1 was markedly associated with the proliferation and migration of VSMCs, and FAK was shown to be involved in the signaling pathways of ITGβ1. ITGα5 did not exert any effects on VSMCs. The results of the present study may provide a possible therapeutic target for the prevention and treatment of early vascular disease associated with VSMCs.