Targeting Endothelial HIF2α/ARNT Expression for Ischemic Heart Disease Therapy.

Ischemic heart disease (IHD) is a major cause of mortality and morbidity worldwide, with novel therapeutic strategies urgently needed. Endothelial dysfunction is a hallmark of IHD, contributing to its development and progression. Hypoxia-inducible factors (HIFs) are transcription factors activated in response to low oxygen levels, playing crucial roles in various pathophysiological processes related to cardiovascular diseases.

A Novel ARNT-Dependent HIF-2α Signaling as a Protective Mechanism for Cardiac Microvascular Barrier Integrity and Heart Function Post-Myocardial Infarction.

Myocardial infarction (MI) significantly compromises the integrity of the cardiac microvascular endothelial barrier, leading to enhanced leakage and inflammation that contribute to the progression of heart failure. While HIF2α is highly expressed in cardiac endothelial cells (ECs) under hypoxic conditions, its role in regulating microvascular endothelial barrier function during MI is not well understood. In this study, we utilized mice with a cardiac-specific deletion of HIF2α, generated through an inducible Cre (Cdh5Cre-ERT2) recombinase system.