Ullah Karim, Wu Rongxue
Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, IL, United States.
Front Physiol. 2021 Jul 5;12:670653. doi: 10.3389/fphys.2021.670653. eCollection 2021.
Endothelial cells (ECs) form a physical barrier between the lumens and vascular walls of arteries, veins, capillaries, and lymph vessels; thus, they regulate the extravasation of nutrients and oxygen from the circulation into the perivascular space and participate in mechanisms that maintain cardiovascular homeostasis and promote tissue growth and repair. Notably, their role in tissue repair is facilitated, at least in part, by their dependence on glycolysis for energy production, which enables them to resist hypoxic damage and promote angiogenesis in ischemic regions. ECs are also equipped with a network of oxygen-sensitive molecules that collectively activate the response to hypoxic injury, and the master regulators of the hypoxia response pathway are hypoxia-inducible factors (HIFs). HIFs reinforce the glycolytic dependence of ECs under hypoxic conditions, but whether HIF activity attenuates or exacerbates the progression and severity of cardiovascular dysfunction varies depending on the disease setting. This review summarizes how HIF regulates the metabolic and angiogenic activity of ECs under both normal and hypoxic conditions and in a variety of diseases that are associated with cardiovascular complications.
内皮细胞（ECs）在动脉、静脉、毛细血管和淋巴管的管腔与血管壁之间形成物理屏障；因此，它们调节营养物质和氧气从循环系统外渗到血管周围间隙，并参与维持心血管稳态以及促进组织生长和修复的机制。值得注意的是，它们在组织修复中的作用至少部分是通过依赖糖酵解产生能量来实现的，这使它们能够抵抗缺氧损伤并促进缺血区域的血管生成。内皮细胞还配备有一个对氧敏感的分子网络，这些分子共同激活对缺氧损伤的反应，而缺氧反应途径的主要调节因子是缺氧诱导因子（HIFs）。缺氧诱导因子在缺氧条件下增强内皮细胞对糖酵解的依赖性，但缺氧诱导因子的活性是减轻还是加剧心血管功能障碍的进展和严重程度，取决于疾病背景。本综述总结了缺氧诱导因子在正常和缺氧条件下以及在与心血管并发症相关的多种疾病中如何调节内皮细胞的代谢和血管生成活性。
