Department of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, China.
Eur Rev Med Pharmacol Sci. 2020 Sep;24(17):9046-9054. doi: 10.26355/eurrev_202009_22850.
Acute myocardial infarction (AMI) is a severe fatal disease throughout the world. Myocardial IR limits the recovery of impaired cardiac function in AMI patients. This study aims to elucidate the role of long non-coding RNA (lncRNA) HOTAIR in myocardial ischemia-reperfusion (IR) and the underlying mechanism, thus providing a novel therapy for AMI.
Myocardial IR model in mice was firstly constructed by LAD. Plasma levels of LDH, CK-MB, HOTAIR, and microRNA-126 in mice were detected. Subsequently, in vitro HR model was constructed in H9c2 cells. Regulatory effects of HOTAIR on proliferative ability, LDH release, and Caspase-3 activity in H2O2-induced H9c2 cells were determined. Relative levels of inflammatory factors in in vitro HR model were measured by enzyme-linked immunosorbent assay (ELISA). The regulatory loop HOTAIR/microRNA-126/SRSF1 was finally verified by Dual-Luciferase reporter assay.
LDH and CK-MB were significantly released in mice with myocardial IR. HOTAIR was upregulated, while microRNA-126 was downregulated in IR mice and H2O2-induced H9c2 cells. Overexpression of HOTAIR stimulated proliferative ability, LDH release, and Caspase-3 activity in H2O2-induced H9c2 cells. Besides, overexpression of microRNA-126 inhibited the release of inflammatory factors in H9c2 cells undergoing HR induction. The regulatory loop HOTAIR/microRNA-126/SRSF1 was identified to influence IR development.
HOTAIR aggravates myocardial IR by competitively binding SRSF1 with microRNA-126.
急性心肌梗死（AMI）是一种严重的致命疾病，在全球范围内都存在。心肌缺血再灌注（IR）损伤限制了 AMI 患者受损心功能的恢复。本研究旨在阐明长链非编码 RNA（lncRNA）HOTAIR 在心肌缺血再灌注损伤中的作用及其潜在机制，为 AMI 提供新的治疗策略。
首先通过 LAD 构建小鼠心肌 IR 模型。检测小鼠血浆中 LDH、CK-MB、HOTAIR 和 microRNA-126 的水平。随后，在 H9c2 细胞中构建体外 HR 模型。检测 HOTAIR 对 H2O2 诱导的 H9c2 细胞增殖能力、LDH 释放和 Caspase-3 活性的影响。通过酶联免疫吸附试验（ELISA）测定体外 HR 模型中炎症因子的相对水平。最后通过双荧光素酶报告基因实验验证 HOTAIR/microRNA-126/SRSF1 调控环路。
心肌 IR 小鼠的 LDH 和 CK-MB 明显释放。IR 小鼠和 H2O2 诱导的 H9c2 细胞中 HOTAIR 上调，而 microRNA-126 下调。HOTAIR 的过表达刺激了 H2O2 诱导的 H9c2 细胞的增殖能力、LDH 释放和 Caspase-3 活性。此外，microRNA-126 的过表达抑制了 HR 诱导的 H9c2 细胞中炎症因子的释放。鉴定出 HOTAIR/microRNA-126/SRSF1 调控环路影响 IR 的发生。
HOTAIR 通过与 microRNA-126 竞争结合 SRSF1 加重心肌 IR。
