Key result
Integrative multi-omics analysis revealed that pulmonary arterial hypertension is characterized by dysregulated mitochondrial metabolic pathways, including accelerated one-carbon metabolism, abnormal TCA cycle flux, and increased oxidative stress.
Why the study?
Pulmonary arterial endothelial cells are mechanistically linked to pulmonary arterial hypertension origins, prompting global proteomics and phosphoproteomics to confirm known pathways and identify new areas of investigation.
Case-Control (n=42)
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.
No takes yet. Share an insight, caveat, or question.
Xu et al. (2019) conducted a case-control in Pulmonary arterial hypertension (n=42). Pulmonary arterial hypertension vs. Healthy controls was evaluated on Differentially expressed proteins, phosphopeptides, and metabolites. Integrative multi-omics analysis revealed that pulmonary arterial hypertension is characterized by dysregulated mitochondrial metabolic pathways, including accelerated one-carbon metabolism, abnormal TCA cycle flux, and increased oxidative stress.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: