HIF-1α调控动脉粥样硬化的研究进展

Advances in hypoxia inducible factor-1α regulating atherosclerosis

摘要:

动脉粥样硬化提供了局部缺氧微环境,缺氧诱导因子1α(HIF-1α)被激活,一方面通过诱导血管内皮生长因子(VEGF)促进病理性血管新生,增加斑块脆弱性；另一方面通过调控巨噬细胞代谢重编程,增强NOD样受体蛋白3(NLRP3)炎症小体活性[促进白细胞介素1β(IL-1β)成熟]及M1型极化,加剧炎症反应。在血管平滑肌细胞中,HIF-1α通过VEGF自分泌、巨噬细胞迁移抑制因子(MIF)和溶质载体家族3成员2(SLC3A2)等途径促进增殖和迁移,同时诱导成骨分化加速血管钙化。在血管内皮细胞中,HIF-1α通过增强单核细胞黏附,并与核因子κB(NF-κB)形成正反馈环路放大氧化应激,进一步破坏内皮稳态。本文总结了HIF-1α通过协调血管生成、炎症放大及细胞表型转化,促进斑块不稳定和血栓风险,为靶向干预提供了分子理论基础。

Abstract:

Atherosclerosis creates a hypoxic microenvironment that activates hypoxia-inducible factor-1α (HIF-1α). This factor promotes pathological angiogenesis via vascular endothelial growth factor (VEGF) induction, increasing plaque vulnerability, while simultaneously exacerbating inflammation through metabolic reprogramming of macrophages, enhanced NOD-like receptor protein 3 (NLRP3) inflammasome activity (driving interleukin-1β (IL-1β) maturation), and M1 polarization. In vascular smooth muscle cells, HIF-1α stimulates proliferation, migration, and osteogenic differentiation via VEGF autocrine signaling, macrophage migration inhibitory factor (MIF), and solute carrier family 3 member 2 (SLC3A2) pathways, accelerating vascular calcification. In vascular endothelial cell, HIF-1α amplifies oxidative stress by enhancing monocyte adhesion and forming a feedback loop with nuclear factor-κB (NF-κB), further disrupting endothelial homeostasis. This paper summarizes that HIF-1α promotes plaque instability and thrombotic risk by coordinating angiogenesis, inflammatory amplification and cellular phenotype transformation, which provides a molecular theoretical basis for targeted intervention.