Mechanism Of Action Of ARB Antihypertensive Drugs On Endothelial Progenitor Cells In Patients With Hypertension

Objective: To clarify the promotive effect of Irbesartan on endothelial progenitor cells and elucidate its mechanism of action,providing a new theoretical and experimental basis for the treatment of cardiovascular diseases with Irbesartan.Methods: Endothelial progenitor cells(EPCs)were stimulated with irbesartan for 24 h.CCK-8 assay was used to determine the proliferation ability of EPCs after different concentrations of irbesartan intervention,and the effect on the ability of cells to migrate,as measured by the Transwell method;Using transcriptomics to find differentially expressed genes,and DO enrichment analysis,GO enrichment analysis,and KEGG enrichment analysis were performed on the differential genes.To explore the omics mechanism of irbesartan promoting the proliferation and migration of EPCs.Specific inhibitors and western blot were used to verify the regulatory mechanism of irbesartan in EPCs.Results:(1)Irbesartan promotes the proliferation and migration of EPCs.(2)The results of transcriptome analysis showed that there were 229 differentially expressed genes,including101 up-regulated genes and 128 down-regulated genes.(3)KEGG enrichment results showed that the differentially expressed genes were mainly enriched in NF-κB signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,Jak-STAT signaling pathway,CGMP-PKG signaling pathway,P53 and other signaling pathways;DO enrichment analysis showed that the differentially expressed genes were mainly enriched in skin system diseases,keratosis,lung cancer,reproductive organ cancer,respiratory system tumors,cellular cancer,cerebrovascular disease,atherosclerotic cardiovascular disease and other diseases;GO enrichment analysis shows that differential genes in biological processes were mainly enriched in GO terms of biological regulation,metabolism,regulation of biological processes and immune response;The differential genes in molecular function were mainly enriched in integration,catalysis,molecular function regulation,transcription regulation,transport activity,etc;The differentially expressed genes in cell components were mainly enriched in cells,organelles,and cell exosomes.(4)Irbesartan activates the MAPK signalling pathway and the use of PD98059,an inhibitor of ERK,inhibits irbesartan-induced proliferation of EPCs and SB203580,an inhibitor of P38,inhibits irbesartan-induced migration of EPCs.(5)Irbesartan enhanced the phosphorylation of p65,and the proliferation and migration induced by EPCs were inhibited by BAY11-7082,an inhibitor of NF-κB.Conclusion:(1)Irbesartan promoted the proliferation and migration of EPCs.(2)Irbesartan was involved in the proliferation of EPCs by activating ERK-NF-κB signaling pathway,and in the migration of EPCs by activating p38-NF-κB signaling pathway.