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High-fat diet (HFD) can cause obesity, inducing dysregulation of the visceral adipose tissue (VAT). This study aimed to explore potential biological pathways and hub genes involved in obese VAT, and for that, bioinformatic analysis of multiple datasets was performed. The expression profiles (GSE30247, GSE167311 and GSE79434) were downloaded from Gene Expression Omnibus. Overlapping differentially expressed genes (ODEGs) between normal diet and HFD groups in GSE30247 and GSE167311 were selected to run protein–protein interaction network, GO and KEGG analysis. The hub genes in ODEGs were screened by Cytoscape software and further verified in GSE79434 and obese mouse model. A total of 747 ODEGs (599 up-regulated and 148 down-regulated) were screened, and the GO and KEGG analysis showed that the up-regulated ODEGs were significantly enriched in inflammatory response and extracellular matrix receptor interaction pathways. On the other hand, the down-regulated ODEGs were involved in metabolic pathways; however, there were no significant KEGG pathways. Furthermore, six hub genes, Mki67, Rac2, Itgb2, Emr1, Tyrobp and Csf1r were acquired. These pathways and genes were verified in GSE79434 and VAT of obese mice. This study revealed that HFD induced VAT expansion, inflammation and fibrosis, and the hub genes could be used as therapeutic biomarkers in obesity. [ABSTRACT FROM AUTHOR]

This study determines whether preconditioning (PC) of human endothelial progenitor cells (hEPCs) with bradykinin promotes infarcted myocardium repair via enhanced activation of B2 receptor (B2R)-dependent Akt/eNOS and increased angiogenesis. hEPCs with or without bradykinin preconditioning (BK-PC) were transplanted into a nude mouse model of acute myocardial infarction. Survival of transplanted cells was assessed using DiD-labeled hEPCs. Infarct size, cardiac function, and angiogenesis were measured 10 d after transplantation. Akt, eNOS, and vascular endothelial growth factor (VEGF) expressions in cardiac tissues were detected by western blotting, and NO production was determined using an NO assay kit. The cell migration and tube formation in cultured hEPCs were determined using transwell chamber and matrigel tube formation assays, respectively. The VEGF levels in the cell supernatant were measured using an enzyme-linked immunosorbent assay kit. BK-PC-hEPCs improved cardiac function, decreased infarct size, and promoted neovascularization 10 d following transplantation. PC increased Akt and eNOS phosphorylation, VEGF expression, and NO production in the ischemic myocardium. The effects of BK-PC were abrogated by HOE140 (B2R antagonist) and LY294002 (Akt antagonist). PC increased hEPC migration, tube formation, and VEGF levels in vitro. Activation of B2R-dependent Akt/eNOS phosphorylation by BK-PC promotes hEPC neovascularization and improves cardiac function following transplantation.