Abstract
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary arterial pressure due to increased pulmonary vascular resistance, secondary to sustained pulmonary vasoconstriction and excessive obliterative pulmonary vascular remodeling. Work over the last decade has led to the identification of a critical role for metabolic reprogramming in the PAH pathogenesis. It is becoming clear that in addition to its role in ATP generation, the mitochondrion is an important organelle that regulates complex and integrative metabolic- and signal transduction pathways. This review focuses on mitochondrial metabolism alterations that occur in deranged pulmonary vessels and the right ventricle, including abnormalities in glycolysis and glucose oxidation, fatty acid oxidation, glutaminolysis, redox homeostasis, as well as iron and calcium metabolism. Further understanding of these mitochondrial metabolic mechanisms could provide viable therapeutic approaches for PAH patients.
Highlights
The 6th World Symposium on Pulmonary Hypertension defines pulmonary hypertension (PH) as mean pulmonary arterial pressure > 20 mmHg at rest in the supine position measured by a right heart catheterization (RHC)
This review mainly focuses on the first group of PH, pulmonary arterial hypertension (PAH)
Mitochondrial modulation of reactive oxygen species (ROS), iron metabolism, and calcium homeostasis participate in controlling the vascular remodeling, right ventricular (RV) hypertrophy (RVH), and hypoxic pulmonary vasoconstriction (HPV), linked to PAH development [6]
Summary
The 6th World Symposium on Pulmonary Hypertension defines pulmonary hypertension (PH) as mean pulmonary arterial pressure (mPAP) > 20 mmHg at rest in the supine position measured by a right heart catheterization (RHC). This review mainly focuses on the first group of PH, pulmonary arterial hypertension (PAH). Dysfunction of various pulmonary vascular cells (PVCs), including endothelial and smooth muscle cells (SMC), is associated with PAH pathobiology [3]. Biomedicines 2022, 10, 341 vasculature and RV dysfunction and PAH development. Our previous work has demonstrated that increased HIF-2α expression in pulmonary vascular endothelial cells plays a pathogenic role in the development of severe PAH [5]. Mitochondrial modulation of reactive oxygen species (ROS), iron metabolism, and calcium homeostasis participate in controlling the vascular remodeling, RV hypertrophy (RVH), and hypoxic pulmonary vasoconstriction (HPV), linked to PAH development [6]. We review the role of metabolic pathways and related mechanisms in PAH and discuss whether these mechanisms may represent potential therapeutic perspectives
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