The role of hypoxia-inducible factors in cardiovascular diseases

Cardiovascular diseases are the leading cause of death worldwide. During the development of cardiovascular diseases, hypoxia plays a crucial role. Hypoxia-inducible factors (HIFs) are the key transcription factors for adaptive hypoxic responses, which orchestrate the transcription of numerous genes involved in angiogenesis, erythropoiesis, glycolytic metabolism, inflammation, and so on. Recent studies have dissected the precise role of cell-specific HIFs in the pathogenesis of hypertension, atherosclerosis, aortic aneurysms, pulmonary arterial hypertension, and heart failure using tissue-specific HIF-knockout or -overexpressing animal models. More importantly, several compounds developed as HIF inhibitors or activators have been in clinical trials for the treatment of renal cancer or anemia; however, little is known on the therapeutic potential of these inhibitors for cardiovascular diseases. The purpose of this review is to summarize the recent advances on HIFs in the pathogenesis and pathophysiology of cardiovascular diseases and to provide evidence of potential clinical therapeutic targets.