Abstract
Pulmonary hypertension (PH) represents a group of disorders characterized by elevated mean pulmonary artery (PA) pressure, progressive right ventricular failure, and often death. Some of the hallmarks of pulmonary hypertension include endothelial dysfunction, intimal and medial proliferation, vasoconstriction, inflammatory infiltration, and in situ thrombosis. The vascular remodeling seen in pulmonary hypertension has been previously linked to the hyperproliferation of PA smooth muscle cells. This excess proliferation of PA smooth muscle cells has recently been associated with changes in metabolism and mitochondrial biology, including changes in glycolysis, redox homeostasis, and mitochondrial quality control. In this review, we summarize the molecular mechanisms that have been reported to contribute to mitochondrial dysfunction, metabolic changes, and redox biology in PH.
Highlights
Received: 21 January 2022Pulmonary hypertension (PH) represents a myriad of disorders characterized by elevated mean pulmonary artery pressure
In a rat model of PH and human pulmonary artery smooth muscle cells (HPASMC) subjected to hypoxia, the inhibition of fatty acid synthase (FAS) by siRNA led to increases in apoptosis and glucose oxidation while the mitochondrial in HPASMC demonstrated normal ROS
Despite a lack of understanding of the events that occur in the early stages of pulmonary arterial hypertension (PAH), emerging data suggest that oxidative stress and inflammation, known to impact vascular cell contractility and proliferation, are linked to nuclear and mitochondrial DNA damage [100]
Summary
Pulmonary hypertension (PH) represents a myriad of disorders characterized by elevated mean pulmonary artery pressure. It is a progressive and, often, a lethal disease in both children and adults. Standard treatment targets different pathways to augment vasodilation [4] Despite these therapeutic interventions, the prognosis is generally poor, necessitating further investigation into the pathogenesis of the aforementioned vascular remodeling to improve novel therapeutic strategies [5]. This review aims to summarizes the current understanding of the role of mitochondrial dysfunction in the development of PH. This will include electron transport chain (ETC) dysfunction and the shift in energy production from mitochondrial oxidative phosphorylation to glycolysis, mitochondrial DNA damage, impaired quality control (biogenesis and mitophagy), imbalances in mitochondrial. A cutting-edge understanding of the mitochondrial metabolic, molecular, and physiologic role in this disease should enable the development of mitochondria-targeted therapies to slow or revert PH development
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