Research Progress on the Mechanism of HIF-2α in Cardiovascular Diseases

doi:10.12114/j.issn.1007-9572.2024.0294

Abstract

Abstract:

Hypoxia plays a crucial role in the development of cardiovascular diseases, and hypoxia-inducible factor (HIF), as a key transcription factor in adaptive hypoxia, coordinates the transcription of many genes involved in angiogenesis, erythropoiesis, glycolysis, and inflammation, etc. Previous studies have focused on the mechanisms related to HIF-1α, and more recent studies have found that HIF-2α also plays an important role in the pathogenesis of myocardial infarction, atherosclerosis, pulmonary hypertension and hypertrophic cardiomyopathy, and that there are dynamic regulatory mechanisms for the expression of HIF-1α and HIF-2α. In this paper, we systematically summarize the role and characteristics of HIF-2α expression in the above diseases: when HIF-2α is up-regulated, it positively affects the repair and prognosis of the disease; and we also discuss the interaction between HIF-1α and HIF-2α mutual antagonism in the regulation of redox status and the necessity of the presence of pro-inflammatory and pro-fibrotic pathways. The purpose of this review is to summarize the recent advances of HIF-2α in cardiovascular diseases and to summarize promising clinical therapeutic targets. It is anticipated that the targeted modulation of HIF-2α will achieve new advancements in the treatment of actual diseases, which will be of considerable significance for the treatment and prognosis enhancement of cardiovascular disorders.

Key words: Cardiovascular diseases, Hypoxia-inducible factor, Hypoxia, Myocardial infarction, Prolyl hydroxylases, Sirtuin 1

摘要：

在心血管疾病的发展过程中，缺氧起着至关重要的作用。缺氧诱导因子（HIF）作为适应性缺氧反应的关键转录因子协调参与血管生成、红细胞生成、糖酵解代谢、炎症等多种基因的转录。既往研究重点聚焦在HIF-1α的相关机制上，而最近的研究发现HIF-2α在心肌梗死、动脉粥样硬化、肺动脉高压和肥厚型心肌病发病机制中也起到重要作用，并且HIF-1α和HIF-2α的表达存在动态的调控机制。本文系统概括了以上疾病中，HIF-2α表达发挥的作用及特点：HIF-2α水平的改变可以对疾病的修复及预后发挥积极影响；并探讨了HIF-1α和HIF-2α相互拮抗作用在调节氧化还原状态和调节促炎和促纤维化途径中存在的必要性。本综述的目的是总结HIF-2α在心血管疾病的最新进展，并总结具有研究前景的临床治疗靶点。期望HIF-2α的定向调节在实际疾病治疗中获得新的进展，这将对心血管疾病的治疗及预后改善具有重大意义。

关键词: 心血管疾病, 缺氧诱导因子, 低氧, 心肌梗死, 脯氨酰羟化酶, 组蛋白去乙酰化酶1

CLC Number:

R 54

ZHAO Zhuo,WANG He. Research Progress on the Mechanism of HIF-2α in Cardiovascular Diseases[J]. Chinese General Practice, 2025, 28(33): 4241-4248. DOI: 10.12114/j.issn.1007-9572.2024.0294.
赵倬,王贺. 缺氧诱导因子2α在心血管系统疾病中的作用机制研究进展[J]. 中国全科医学, 2025, 28(33): 4241-4248. DOI: 10.12114/j.issn.1007-9572.2024.0294.

Figures/Tables 3

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