Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Fujian Medical University, Fengze, Quanzhou 362000, China.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Taijiang, Fuzhou 350005, China.
Aging (Albany NY). 2021 Feb 11;13(6):8068-8077. doi: 10.18632/aging.202480.
miRNAs play critical roles in the regulation of many cardiovascular diseases. However, its role and potential mechanism in cardiac injury caused by obstructive sleep apnea (OSA) remain poorly elucidated. In the present study, we aimed to investigate the effects of miR-3574 on cardiomyocyte injury under intermittent hypoxia (IH).
We confirmed that IH inhibited cell viability, induced cell apoptosis and suppressed miR-3574 expression in the H9c2. miR-3574 overexpression could ameliorate the effects of IH on the cell viability and cell apoptosis in the H9c2. Axin1 was a target gene of miR-3574, and miR-3574 overexpression reduced the expression of Axin1. miR-3574 could inhibit the IH-induced cardiomyocyte injury via downregulating Axin1. However, Axin1 could partially reverse these effects of miR-3574.
Our study first reveals that miR-3574 could alleviate IH-induced cardiomyocyte injury by targeting Axin1, which may function as a novel and promising therapy target for OSA-associated cardiovascular diseases.
H9c2 were exposed to IH condition. CCK-8 assay was applied to determine cell viability of H9c2. qRT-PCR was conducted to measure the expression level of mRNA and miRNA. Western blot assay was then performed to detect the protein levels. Finally, we used dual-luciferase reporter assay identify the potential target of miR-3574.
miRNAs 在许多心血管疾病的调控中发挥着关键作用。然而,其在阻塞性睡眠呼吸暂停(OSA)引起的心肌损伤中的作用和潜在机制仍不清楚。本研究旨在探讨 miR-3574 在间歇性低氧(IH)下对心肌细胞损伤的影响。
我们证实 IH 抑制细胞活力,诱导细胞凋亡,并抑制 H9c2 中的 miR-3574 表达。miR-3574 的过表达可以改善 IH 对 H9c2 细胞活力和细胞凋亡的影响。Axin1 是 miR-3574 的靶基因,miR-3574 的过表达降低了 Axin1 的表达。miR-3574 可以通过下调 Axin1 抑制 IH 诱导的心肌细胞损伤。然而,Axin1 可以部分逆转 miR-3574 的这些作用。
本研究首次揭示 miR-3574 可以通过靶向 Axin1 减轻 IH 诱导的心肌细胞损伤,这可能为 OSA 相关心血管疾病提供新的有前途的治疗靶点。
H9c2 暴露于 IH 条件下。CCK-8 测定法用于测定 H9c2 的细胞活力。qRT-PCR 用于测量 mRNA 和 miRNA 的表达水平。然后进行 Western blot 测定以检测蛋白水平。最后,我们使用双荧光素酶报告基因测定法鉴定 miR-3574 的潜在靶标。