Biological Regulation of HIF-1α and Its Role in Therapeutic Angiogenesis for Treatment of Ischemic Cardiovascular Disease

Hypoxia, characterized by insufficient oxygen saturation, triggers a wide array of vascular responses aimed at enhancing cell survival and proliferation. This process is primarily driven by the activation of oxygen-sensing hypoxia-inducible factors (HIFs). HIF-1α, a key mediator in this context, plays a crucial role in vascular restructuring in response to low oxygen tension and oxygen-independent signaling pathways, making it a promising therapeutic target for ischemic cardiovascular diseases such as peripheral artery disease and coronary artery disease. In this review, we explore both oxygen-dependent and oxygen-independent mechanisms of HIF-1α regulation, the role of the HIF protein family in vessel collateralization, and translational efforts to leverage HIF-1α's pivotal role in hypoxia signaling for the development of clinical treatments for ischemic cardiovascular disease.