A Biochemical Approach to Understand the Pathogenesis of Advanced Pulmonary Arterial Hypertension: Metabolomic Profiles of Arginine, Sphingosine-1-Phosphate, and Heme of Human Lung

PloS One
Yidan D ZhaoMarc de Perrot

Abstract

Pulmonary arterial hypertension (PAH) is a vascular disease characterized by persistent precapillary pulmonary hypertension (PH), leading to progressive right heart failure and premature death. The pathological mechanisms underlying this condition remain elusive. Analysis of global metabolomics from lung tissue of patients with PAH (n = 8) and control lung tissue (n = 8) leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted arginine pathways with increased Nitric oxide (NO) and decreased arginine. Our results also showed specific metabolic pathways and genetic profiles with increased Sphingosine-1-phosphate (S1P) metabolites as well as increased Heme metabolites with altered oxidative pathways in the advanced stage of the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to the vascular remodeling in severe pulmonary hypertension. Profiling metabolomic alterations of the PAH lung has provided a new understanding of the pathogenic mechanisms of PAH, which benefits therapeutic targeting to specific metabolic pathways involved in the progression...Continue Reading

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Citations

Jan 23, 2016·Journal of the American College of Cardiology·Enrique CalvoJesús Vázquez
Jun 24, 2017·Antioxidants & Redox Signaling·Angelo D'AlessandroKurt R Stenmark
Aug 5, 2017·Respiratory Research·Mengyuan KanBlanca E Himes
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Jun 7, 2019·Antioxidants & Redox Signaling·Olga RafikovaRuslan Rafikov
Oct 20, 2020·Medicinal Research Reviews·Achini K VidanapathiranaStephen J Nicholls

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Datasets Mentioned

BETA
GSE53408

Methods Mentioned

BETA
gene array
gene

Software Mentioned

Partek Genomics Suite
Affymetrix

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