IntroductionMicroRNAs play crucial roles in various types of diseases. However, to date, no information about the role of miR-497 in the development of atherosclerosis has been reported. This study investigated the possible role of miR-497 in vascular endothelial cell injury during the early stage of atherosclerosis.Materials and MethodsThe expression level of miR-497 in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL was detected using qRT-PCR. To perform gain of function and loss of function analyses, miR-497 mimics were transfected into HUVECs, and miR-497 inhibitors were transfected into HUVECs stimulated with ox-LDL. Flow cytometry was used to analyze cell cycle progression and apoptosis. EdU and CCK-8 assays were employed to detect DNA synthesis and cell proliferation, respectively. After bioinformatics prediction, a dual Luciferase Reporter assay was used to analyze the direct target genes of miR-497. The mRNA and protein levels of the target genes were detected using qRT-PCR and western blot analyses, respectively. Caspase-9/3 activity was analyzed to determine the mechanism of endothelial dysfunction.ResultsWe showed that miR-497 was significantly upregulated in HUVECs stimulated with ox-LDL. Ectopic expression of miR-497 suppressed cell proliferation, induced apoptosis and increased the activity of caspase-9/3. After verification, Bcl2 and CCND2 were shown to be direct target genes of miR-497 in HUVECs. MiR-497 significantly suppressed cell proliferation by arresting the cell cycle through the CCND2 protein and induced apoptosis through the Bcl2/Bax-caspase9-caspase3 pathway.ConclusionOverall, our study shows that miR-497 might play a role in the development of atherosclerosis by inducing apoptosis and suppressing the proliferation of vascular endothelial cells. Therefore, miR-497 could be a potential therapeutic target for the treatment of atherosclerosis.

Increasing evidence suggests that microRNAs (miRNAs) play important roles in impaired endothelial cell (EC) angiogenesis during aging. However, their exact roles in the aging process remain unclear. We aimed to determine whether miRNAs cause angiogenesis defects in ECs during aging and to uncover the underlying mechanisms. To study the miRNA-induced changes in ECs during aging, we performed microarray analyses on arterial ECs collected from young and aging mice. Using qRT–PCR, we showed that microRNA-125a-5p (mir-125a-5p) expression was approximately 2.9 times higher in old endothelial cells (OECs) compared with samples collected from young animals. Western blot assays showed a lower expression level of an mir-125a-5p target known as related transcriptional enhancer factor-1 (RTEF-1) in OECs compared with its expression levels in young cells. Overexpression of mir-125a-5p in young endothelial cells (YECs) using pre-mir-125a-5p caused the downregulation of RTEF-1, endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) and resulted in impaired angiogenesis, as evidenced by spheroid sprouting and tube formation assays in vitro. Conversely, repression of mir-125a-5p in OECs using anti-mir-125a-5p increased RTEF-1, eNOS and VEGF expression and improved EC angiogenesis. Importantly, impaired angiogenesis caused by knock-down of RTEF-1 was not efficiently rescued by anti-mir-125a-5p. Dual-luciferase reporter gene analysis showed that RTEF-1 is a direct target of mir-125a-5p, which regulates angiogenesis by repressing RTEF-1 expression and modulating eNOS and VEGF expression. These findings indicate that mir-125a-5p and RTEF-1 are potential therapeutic targets for improving EC-mediated angiogenesis in elderly individuals.

For infrapopliteal arterial occlusive disease, primary stenting has the same 1-year benefits as PTA. There is insufficient evidence to support the superiority of either method. Primary stenting is associated with a trend toward higher primary patency and lower secondary patency. Further large-scale prospective randomized trials should produce more reliable results.

Background: This study investigated whether expanding waist circumference (WC) is causally associated with an elevated risk of coronary heart disease (CHD), using a two-sample Mendelian randomization (MR) study through integrating summarized data from genome-wide association study. Methods: The data included in this analysis were mainly from the Genetic Investigation of ANthropometric Traits (GIANT), Consortium and Coronary ArteryDisease Genome wide Replication, and Meta-analysis plus the Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) Consortium. Three statistical approaches, inverse-variance weighted (IVW), weighted median, and MR-Egger regression method were conducted to assess the casual relationship. The exposure was WC, measured by 46 single-nucleotide polymorphisms from GIANT and the outcome was the risk of CHD. Then, we used the genetic data from Neale Lab and TAG to infer whether WC causally affected the established risk factors of CHD. Results: The IVW method presented that genetically predicted WC was positively casually associated with CHD (odds ratio [OR]: 1.57, 95% CI = 1.33-1.84; p = 4.81e-08), which was consistent with the result of weighted median and MR-Egger regression. MR-Egger regression indicated that there was no directional horizontal pleiotropy to violate the MR assumption. Additionally, expanded WC was also associated with higher risk of hypertension and diabetes, higher cholesterol, more smoking intensity, and decreased frequency of physical activity. Conclusion: Our analysis provided strong evidence to indicate a causal relationship between WC and increased risk of CHD. K E Y W O R D Scoronary heart disease, Mendelian randomization, waist circumference 2 of 11 | CHEN Et al.

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