Laboratory of Cardiovascular Diseases, Guangdong Medical University, Zhanjiang, Guangdong 524000, P.R. China.
Guangdong Key Laboratory of Age‑related Cardiac and Cerebral Diseases, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China.
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.11991. Epub 2021 Mar 24.
Myocardial ischemia‑reperfusion injury (MIRI) is a severe injury to the ischemic myocardium following the recovery of blood flow. Currently, there is no effective treatment for MIRI in clinical practice. Over the past two decades, biological studies of hypoxia and hypoxia‑inducible factor‑1α (HIF‑1α) have notably improved understanding of oxygen homeostasis. HIF‑1α is an oxygen‑sensitive transcription factor that mediates adaptive metabolic responses to hypoxia and serves a pivotal role in MIRI. In particular, previous studies have demonstrated that HIF‑1α improves mitochondrial function, decreases cellular oxidative stress, activates cardioprotective signaling pathways and downstream protective genes and interacts with non‑coding RNAs. The present review summarizes the roles and associated mechanisms of action of HIF‑1α in MIRI. In addition, HIF‑1α‑associated MIRI intervention, including natural compounds, exosomes, ischemic preconditioning and ischemic post‑processing are presented. The present review provides evidence for the roles of HIF‑1α activation in MIRI and supports its use as a therapeutic target.
心肌缺血再灌注损伤（MIRI）是指缺血心肌血流恢复后发生的严重损伤。目前，临床上尚无针对 MIRI 的有效治疗方法。在过去的二十年中，对缺氧和缺氧诱导因子-1α（HIF-1α）的生物学研究显著提高了人们对氧平衡的认识。HIF-1α 是一种氧敏感转录因子，介导缺氧时的适应性代谢反应，在 MIRI 中起关键作用。特别是，先前的研究表明 HIF-1α 可改善线粒体功能，降低细胞氧化应激，激活心脏保护信号通路和下游保护性基因，并与非编码 RNA 相互作用。本综述总结了 HIF-1α 在 MIRI 中的作用及其相关作用机制。此外，还介绍了与 HIF-1α 相关的 MIRI 干预措施，包括天然化合物、外泌体、缺血预处理和缺血后处理。本综述为 HIF-1α 激活在 MIRI 中的作用提供了证据，并支持将其用作治疗靶点。
