ABSTRACT
The high metabolic demand of the myocardium makes it highly reliant on oxygen for energy. Even moderate hypoxia leads to a deficiency of oxygen in the myocardium. Hypoxia not only affects the right ventricle (RV) myocardium directly, but also promotes pathological conditions that severely stress the RV, such as pulmonary arterial hypertension (PAH). Thus, hypoxia profoundly impacts RV function. Many signaling pathways regulated by hypoxia, including HIF-1α, affect the pulmonary vasculature, and the RV cardiomyocyte. Hypoxia signaling pathways intersect to affect inflammation, extracellular matrix remodeling, mitochondrial function, and energy generation; all of which contribute to RV dysfunction in PAH and other conditions (Figure). Some pathways that are active in the physiological hypoxia of the fetus are reactivated in the pathological hypoxia of PAH and the failing RV. Some of these signaling pathways may constitute therapeutic targets to improve RV function, especially in the setting of PAH.
