Atherosclerosis is a highly prevalent disease that can significantly increase the risk of major vascular events, such as myocardial or cerebral infarctions. The anoxemia theory states that a disparity between oxygen supply and demand contributes to atherosclerosis. Hypoxia inducible factor-1 (HIF-1) is a heterodimeric protein, part of the basic helix-loop-helix family and one of the main regulators of cellular responses in a low‑oxygen environment. It plays a key role in the development of atherosclerosis through cell-specific responses, acting on endothelial cells, vascular smooth muscle cells (SMCs) and macrophages. Through the upregulation of VEGF, NO, ROS and PDGF, HIF-1 is able to cause endothelial cell dysfunction, proliferation, angiogenesis and inflammation. Activation of the NF-kB pathway in endothelial cells is an important contributor to inflammation and positively feedbacks to HIF-1. HIF-1 also plays a significant role in both the proliferation and migration of smooth muscle cells – two important features of atherosclerosis, while the formation of foam cells (lipid-laden macrophages) is also a critical step in atherosclerosis and mediated by HIF-1 through various mechanisms such as dysfunctional efflux pathways in macrophages. Overall, HIF-1 exerts its effect on the pathogenesis of atherosclerosis via a variety of molecular and cellular events in the process. In this review article, we examine the effects HIF-1 on vascular cells and macrophages in the development of atherosclerosis, highlighting the environmental cues and signalling pathways that control HIF-1 expression/activation within the vasculature. We will highlight the potential of HIF-1 as a therapeutic target on the disease development.

动脉粥样硬化是一种高度流行的疾病，可显着增加主要血管事件的风险，例如心肌或脑梗塞。缺氧理论指出，氧气供需之间的差异会导致动脉粥样硬化。缺氧诱导因子-1 (HIF-1) 是一种异二聚体蛋白，是基本螺旋-环-螺旋家族的一部分，也是低氧环境中细胞反应的主要调节因子之一。它通过细胞特异性反应，作用于内皮细胞、血管平滑肌细胞 (SMC) 和巨噬细胞，在动脉粥样硬化的发展中起关键作用。通过上调 VEGF、NO、ROS 和 PDGF，HIF-1 能够引起内皮细胞功能障碍、增殖、血管生成和炎症。内皮细胞中 NF-kB 通路的激活是炎症的重要贡献者，并且对 HIF-1 有正反馈。HIF-1 在平滑肌细胞的增殖和迁移中也发挥着重要作用——这是动脉粥样硬化的两个重要特征，而泡沫细胞（载脂巨噬细胞）的形成也是动脉粥样硬化的关键步骤，由 HIF-1 介导通过各种机制，例如巨噬细胞中功能失调的外排途径。总体而言，HIF-1 通过过程中的各种分子和细胞事件对动脉粥样硬化的发病机制产生影响。在这篇综述文章中，我们研究了 HIF-1 在动脉粥样硬化发展过程中对血管细胞和巨噬细胞的影响，突出控制脉管系统内 HIF-1 表达/激活的环境线索和信号通路。我们将强调 HIF-1 作为疾病发展的治疗靶点的潜力。