Ornithine is a key mediator in hyperphosphatemia-mediated human umbilical vein endothelial cell apoptosis: Insights gained from metabolomics
Abstract
Hyperphosphatemia is associated with accelerated vascular endothelial dysfunction in patients with chronic kidney disease (CKD). The purpose of this study is to investigate the molecular mechanisms underlying hyperphosphatemia-caused endothelial dysfunction. The metabolic fingerprinting of human umbilical vein endothelial cells (HUVECs) subjected to hyperphosphatemia was characterized using an integrated metabolomics approach. HUVECs cultured in physiologically simulated hyperphosphatemia with or without phosphonoformic acid, a sodium-dependent phosphate transporter inhibitor (N=6) were collected for metabolomics analysis. Multivariate principle component analysis and partial least squares discriminant analysis were applied to analyze the metabolic data. The key metabolites were confirmed by quantitative analysis using liquid chromatography coupled with tandem mass spectrometer (LC-MS/MS). 36 metabolites were significantly altered in HUVECs following the challenges of hyperphosphatemia mimic, involving several metabolic pathways (all P<0.05). Among them, ornithine increased significantly in the HUVECs mediated by hyperphosphatemia mimic, and its levels positively correlated with cell apoptosis rate (r=0.674, P=0.002), and sever...Continue Reading
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis