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Pulmonary arterial hypertension (PAH) is characterized by impaired regulation of pulmonary hemodynamics and vascular growth. Alterations of metabolism and bioenergetics are increasingly recognized as universal hallmarks of PAH, as metabolic abnormalities are identified in lungs and hearts of patients, animal models of the disease, and cells derived from lungs of patients. Mitochondria are the primary organelle critically mediating the complex and integrative metabolic pathways in bioenergetics, biosynthetic pathways, and cell signaling. Here, we review the alterations in metabolic pathways that are linked to the pathologic vascular phenotype of PAH, including abnormalities in glycolysis and glucose oxidation, fatty acid oxidation, glutaminolysis, arginine metabolism, one-carbon metabolism, the reducing and oxidizing cell environment, and the tricarboxylic acid cycle, as well as the effects of PAH-associated nuclear and mitochondrial mutations on metabolism. Understanding of the metabolic mechanisms underlying PAH provides important knowledge for the design of new therapeutics for treatment of patients. [ABSTRACT FROM AUTHOR]

Pulmonary arterial endothelial cells (PAEC) are mechanistically linked to origins of pulmonary arterial hypertension (PAH). Here, global proteomics and phosphoproteomics of PAEC from PAH (n = 4) and healthy lungs (n = 5) were performed using LC-MS/MS to confirm known pathways and identify new areas of investigation in PAH. Among PAH and control cells, 170 proteins and 240 phosphopeptides were differentially expressed; of these, 45 proteins and 18 phosphopeptides were located in the mitochondria. Pathologic pathways were identified with integrative bioinformatics and human protein-protein interactome network analyses, then confirmed with targeted proteomics in PAH PAEC and non-targeted metabolomics and targeted high-performance liquid chromatography of metabolites in plasma from PAH patients (n = 30) and healthy controls (n = 12). Dysregulated pathways in PAH include accelerated one carbon metabolism, abnormal tricarboxylic acid (TCA) cycle flux and glutamate metabolism, dysfunctional arginine and nitric oxide pathways, and increased oxidative stress. Functional studies in cells confirmed abnormalities in glucose metabolism, mitochondrial oxygen consumption, and production of reactive oxygen species in PAH. Altogether, the findings indicate that PAH is typified by changes in metabolic pathways that are primarily found in mitochondria. [ABSTRACT FROM AUTHOR]

The article presents information on a hypothesis which studies that phenotype of Primary Pulmonary Hypertension (PPH) edothelial cells in angiogenesis causes Primary Pulmonary Hypertension (PPH) disease. The article authors say that they developed hypothesis to substantiate that PPH cells in angiogenesis causes PPH . For this research they isolated and characterized Primary Pulmonary Artery Endothelial Cells (PAECs) from control and PPH lungs. The article author says that in the absence of growth factors, PPH PAECs have is three times greater in PPH patients.