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

doi:10.12114/j.issn.1007-9572.2024.0294

中国全科医学 ›› 2025, Vol. 28 ›› Issue (33): 4241-4248.DOI: 10.12114/j.issn.1007-9572.2024.0294

所属专题：心血管最新文章合辑

• 综述与专论 • 上一篇

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

赵倬¹^,², 王贺¹^,²^,^*()

1．450000　河南省郑州市，河南中医药大学第一附属医院心脏中心　国家区域（中医）心血管诊疗中心
2．450000　河南省郑州市，河南中医药大学　中西医防治重大疾病河南省协同创新中心

收稿日期:2024-08-01 修回日期:2024-09-01 出版日期:2025-11-20 发布日期:2025-09-17
通讯作者: 王贺
作者贡献：
赵倬负责文章的构思与设计、研究资料的收集与整理、论文撰写、绘图；王贺负责论文修订、文章的质量控制及审校，对文章整体负责、监督管理。
基金资助:
国家自然科学基金资助项目(82274316)

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

ZHAO Zhuo¹^,², WANG He¹^,²^,^*()

1. Heart Center, the First Affiliated Hospital of Henan University of CM/National Regional (Traditional Chinese Medicine) Cardiovascular Diagnosis and Treatment Center, Zhengzhou 450000, China
2. Henan University of CM/Henan Collaborative Innovation Center for Prevention and Treatment of Major Diseases, Zhengzhou 450000, China

Received:2024-08-01 Revised:2024-09-01 Published:2025-11-20 Online:2025-09-17
Contact: WANG He

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摘要/Abstract

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

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

中图分类号:

R 54

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.
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.

图/表 3

图1 无氧条件下HIF-α机制图注：HIF-α=缺氧诱导因子α，ARNT=芳烃受体核转运子。

Figure 1 HIF-α mechanism diagram under hypoxic cinditions

图2 HIF-2α结构图注：bHLH=碱性螺旋-环-螺旋，PAS=Per-ARNT-Sim，Hsp90=热休克蛋白，ODD=氧依赖降解结构域，TAD=反式激活结构域，pVHL=E3泛素连接酶复合物的底物识别部分（靶向HIF-2α进行泛素化降解），Sirt1=沉默调节蛋白（去乙酰化HIF-α），HAF=泛素化HIF-α，FIH-1=天冬氨酸羟化酶。

Figure 2 HIF-2α structurel diagram

图3 药物作用原理注：SGLT2=钠-葡萄糖共转运蛋白2，PHD=脯氨酰羟化酶。

Figure 3 Principle of drugs

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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

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

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[10]	韩正, 孙梦, 傅方琳, 潘姚佳, 王为强. 50岁及以上人群三酰甘油葡萄糖指数与心血管代谢性共病关系的研究[J]. 中国全科医学, 2025, 28(18): 2278-2284.
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[14]	聂媛媛, 方达, 徐浩, 杨东辉, 毕艳, 顾天伟. 不同肝纤维化风险的2型糖尿病患者临床特征及心血管疾病风险研究[J]. 中国全科医学, 2025, 28(15): 1847-1854.
[15]	邓毅凡, 何胜虎, 张晶, 朱莉. 钠-葡萄糖共转运蛋白2抑制剂对急性心肌梗死患者经皮冠状动脉介入治疗术后主要不良心血管事件发生的影响：一项Meta分析[J]. 中国全科医学, 2025, 28(15): 1884-1890.