Pulmonary Hypertension and the Right Ventricle: The Roles of Mitochondrial Reactive Oxygen Species in Causing Further Right Ventricular Mitochondrial Changes

Pulmonary hypertension (PH) is a fatal disorder that is gaining considerable attention as an imminent global health concern. It is defined as an elevated mean pulmonary arterial pressure of ≥25 mm Hg at rest, while its pathogenesis is not well understood due to the involvement of complex molecular pathways. These pathways generally lead to pulmonary arterial smooth muscle cell proliferation, endothelial cell resistance to apoptosis, and vasoconstriction. These processes obliterate the lumens of pulmonary arterioles and thus increases mean pulmonary arterial pressure. This results in elevated right ventricular (RV) afterload that puts in motion a range of RV changes, in particular, RV mitochondrial changes. Of note, PH affects the RV in such a manner that RV mitochondria produce excessive reactive oxygen species (ROS). In this chapter, the roles of RV mitochondrial ROS in PH related RV failure are comprehensively discussed. Accumulating evidence is critically reviewed in relation to the impact of mitochondrial ROS on (a) RV remodelling, (b) RV mitochondrial gene expression and dynamics, and (b) RV mitochondrial respiration.