Vascular Program, Institute for Cell Engineering; Departments of Pediatrics, Medicine, Oncology, Radiation Oncology, and Biological Chemistry; and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; email:
Annu Rev Physiol. 2014;76:39-56. doi: 10.1146/annurev-physiol-021113-170322. Epub 2013 Aug 21.
Cardiac function is required for blood circulation and systemic oxygen delivery. However, the heart has intrinsic oxygen demands that must be met to maintain effective contractility. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis in all metazoan species. HIF-1 controls oxygen delivery, by regulating angiogenesis and vascular remodeling, and oxygen utilization, by regulating glucose metabolism and redox homeostasis. Analysis of animal models suggests that by activation of these homeostatic mechanisms, HIF-1 plays a critical protective role in the pathophysiology of ischemic heart disease and pressure-overload heart failure.
心脏功能对于血液循环和全身氧气输送至关重要。然而,心脏本身也有氧气需求,必须得到满足才能维持有效的收缩能力。缺氧诱导因子 1(HIF-1)是一种转录因子,作为所有后生动物物种中氧气稳态的主调控因子发挥作用。HIF-1 通过调节血管生成和血管重塑来控制氧气输送,通过调节葡萄糖代谢和氧化还原稳态来控制氧气利用。对动物模型的分析表明,通过激活这些稳态机制,HIF-1 在缺血性心脏病和压力超负荷性心力衰竭的病理生理学中发挥着关键的保护作用。