Abstract
BackgroundEndothelial progenitor cells (EPCs) play essential roles in vascular repair. Our previous study suggests OSS would lead EPCs transdifferention into the mesenchymal cell that aggravates pathological vascular remodeling. The primary purpose of this study was to apply OSS in vitro in EPCs and then explore proteins, metabolites, and the protein-metabolite network of EPCs.MethodsEndothelial progenitor cells were kept in static or treated with OSS. For OSS treatment, the Flexcell STR-4000 parallel plate flow system was used to simulate OSS for 12 h. Subsequently, an untargeted metabolomic LC/MS analysis and a TMT-labeled quantitative proteomic analysis were performed.ResultsA total of 4,699 differentially expressed proteins (DEPs) were identified, among which 73 differentially expressed proteins were potentially meaningful (P < 0.05), with 66 upregulated and 7 downregulated expressions. There were 5,664 differential metabolites (DEMs), of which 401 DEMs with biologically potential marker significance (VIP > 1, P < 0.05), of which 137 were upregulated and 264 were downregulated. The Prison correlation analysis of DEPs and DEMs was performed, and the combined DEPs–DEMs pathway analyses of the KGLM database show 39 pathways. Among the DEPs, including the Phosphoserine phosphatase (PSPH), Prostaglandin E synthase 3 (PTGES3), Glutamate–cysteine ligase regulatory subunit (GCLM), Transaldolase (TALDO1), Isocitrate dehydrogenase 1 (IDH1) and Glutathione S-transferase omega-1 (GSTO1), which are significantly enriched in the citric acid cycle (TCA cycle) and fatty acid metabolic pathways, promoting glycolysis and upregulation of fatty acid synthesis. Moreover, we screened the 6 DEPs with the highest correlation with DEMs for predicting the onset of early AS and performed qPCR to validate them.ConclusionThe comprehensive analysis reveals the following main changes in EPCs after the OSS treatment: dysregulation of glutamate and glycine metabolism and their transport/catabolic related proteins. Disorders of fatty acid and glycerophospholipid metabolism accompanied by alterations in the corresponding metabolic enzymes. Elevated expression of glucose metabolism.
Highlights
The occurrence and mortality of cardiovascular disease (CVD) are always high, endangering public health and safety
We found that high glutamate–cysteine ligase regulatory subunit (GCLM) expression after oscillatory shear stress (OSS) promoted cysteine and methionine metabolism, resulting in increased serum concentrations of Hcy
We found that the combination of differential genes phosphoserine phosphatase (PSPH), prostaglandin E synthase (PTGES3), GCLM, TALDO1, isocitrate dehydrogenase cytoplasmic (IDH1), and glutathione S-transferase omega-1 (GSTO1) has the ability to act as an early biomarker for the development of AS
Summary
The occurrence and mortality of cardiovascular disease (CVD) are always high, endangering public health and safety. Metabolic diseases caused by the accumulation of lipids from the intima leads to the formation of plaques, which are prone to form in the opening, bifurcation, and bending of an artery. This formation is closely related to the anatomy and hemodynamic characteristics of these portions of vessels (Cheng et al, 2006), which indicates shear stress (SS) plays an essential role in the development of these diseases. Endothelial progenitor cells (EPCs) play essential roles in vascular repair. Our previous study suggests OSS would lead EPCs transdifferention into the mesenchymal cell that aggravates pathological vascular remodeling. The primary purpose of this study was to apply OSS in vitro in EPCs and explore proteins, metabolites, and the protein-metabolite network of EPCs
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