Molecular basis and clinical implications of HIFs in cardiovascular diseases

Oxygen maintains the homeostasis of an organism in a delicate balance in different tissues and organs. Under hypoxic conditions, hypoxia-inducible factors (HIFs) are specific and dominant factors in the spatiotemporal regulation of oxygen homeostasis. As the most basic functional unit of the heart at the cellular level, the cardiomyocyte relies on oxygen and nutrients delivered by the microvasculature to keep the heart functioning properly. Under hypoxic stress, HIFs are involved in acute and chronic myocardial pathology because of their spatiotemporal specificity, thus granting them therapeutic potential. Most adult animals lack the ability to regenerate their myocardium entirely following injury, and complete regeneration has long been a goal of clinical treatment for heart failure. The precise manipulation of HIFs (considering their dynamic balance and transformation) and the development of HIF-targeted drugs is therefore an extremely attractive cardioprotective therapy for protecting against myocardial ischemic and hypoxic injury, avoiding myocardial remodeling and heart failure, and promoting recovery of cardiac function.