Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, PR China.
Beijing An Zhen Hospital, Capital Medical University, Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, 100029, China.
Biochem Biophys Res Commun. 2021 Apr 9;548:182-188. doi: 10.1016/j.bbrc.2021.02.034. Epub 2021 Feb 26.
Intermittent hypoxia (IH), a main characteristic of obstructive sleep apnea (OSA) syndrome, is an independent risk factor of cardiovascular complications. However, the mechanism has not been fully elucidated. Growing evidence has revealed alterations of extracellular vesicle (EV) contents, mostly miRNAs, playing a pathogenic role in cardiovascular complications. In current study, we attempt to compare the disparity of myocardial EV miRNA components after IH or normoxia treatment and determine whether EVs from IH-treated cardiomyocytes could affect endothelial function. 63 differentially expressed miRNAs were identified in EVs from IH-exposed cardiomyocytes by miRNA chip assay. Among them, 16 miRNAs with homologous sequence in mouse and human were verified by qPCR assay and 11 miRNAs were proved with the same tendency as miRNA chip assay. KEGG predicted that the function of differentially expressed miRNA was enriched to Akt signaling pathway. Notably, EVs from IH-exposed cardiomyocytes dramatically impaired endothelial-dependent relaxation and inhibited Akt/eNOS expression in endothelial cells. This study provides the first evidence that IH significantly alters myocardial EV miRNA composition and reveals a novel role of myocardial EVs in endothelial function under IH status, which will help to understand the OSA- or IH-related endothelial dysfunction from a new scope.
间歇性低氧（IH）是阻塞性睡眠呼吸暂停（OSA）综合征的主要特征，是心血管并发症的独立危险因素。然而，其机制尚未完全阐明。越来越多的证据表明，细胞外囊泡（EV）内容物的改变，主要是 miRNAs，在心血管并发症中发挥致病作用。在本研究中，我们试图比较 IH 或常氧处理后心肌 EV miRNA 成分的差异，并确定 IH 处理的心肌细胞来源的 EV 是否会影响内皮功能。miRNA 芯片检测到 IH 暴露的心肌细胞来源的 EV 中有 63 个差异表达的 miRNA。其中，通过 qPCR 检测验证了与小鼠和人类同源序列的 16 个 miRNA，11 个 miRNA 的趋势与 miRNA 芯片检测一致。KEGG 预测差异表达 miRNA 的功能富集到 Akt 信号通路。值得注意的是，IH 暴露的心肌细胞来源的 EV 显著损害内皮依赖性舒张，并抑制内皮细胞中 Akt/eNOS 的表达。本研究首次提供了证据，证明 IH 显著改变了心肌 EV miRNA 的组成，并揭示了 IH 状态下心肌 EV 在内皮功能中的新作用，这将有助于从新的角度理解 OSA 或 IH 相关的内皮功能障碍。
