The peroxisome proliferator activated receptor γ agonist pioglitazone can improve adhesion of endothelial progenitor cells from bone marrow in rat model of metaboic syndrome and its mechanism exploration

Objective To explore whether peroxisome proliferator activated receptor γ (PPARγ) agonists pioglitazone (PIO) could affect the adhesion ability of endothelial progenitor cells (EPCs) from bone marrow in a rat model of metaboic syndrome, and further to explore the mechanism in vivo and ex vivo. Methods Diet-induced rat model of metaboic syndrome was established. EPCs were cultured using density gradient centrifugation and differential velocity adherent methods, and identified with double dyeing method. The adhesion ability of EPCs from bone marrow was compared by cell counting method among three groups incuding control group, metaboic syndrome group and PIO group. EPCs from bone marrow of rats with metaboic syndrome were cultured for 7 days, then were divided into 5 groups, respectively given PIO; PIO and PPAR antagonists GW9662; PIO and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) channel blocker Wortmannin; PIO and extracellular signal-regulated kinase (ERK) channel blocker PD98059, and a blank control group. Then the adhesion ability of EPCs was tested. Results As compared with the blank control group, the adhesion ability of EPCs was decreased in metaboic syndrome group (21.13±2.77 vs. 33.20±3.06, t=3.516, P=0.000). PIO treatment could improve the adhesion ability of EPCs (27.16±2.27 vs. 21.13±2.77, t=2.917, P=0.007). Ex vivo studies also showed PIO could improve the adhesion ability of EPCs cultured for 7 days (35.5±3.56 vs. 21.3±2.78, t=4.512, P=0.006). The effect disappeared when there were PPAR-γ antagonist GW9662 and PI3K/Akt channel blocker Wortmannin (22.50±3.16 vs. 35.50±3.56, t=4.512, P=0.006; 23.10±3.11 vs. 35.50±3.56, t=4.011, P=0.008), but the effect didn’t disappare when there was ERK channel blocker PD98059 (34.90±3.46 vs. 35.50±3.56, t=0.355, P=0.211). Conclusion The EPCs adhesion ability was decreased in rat model of metaboic syndrome. PIO could improve EPCs adhesion ability, which was possibly mediated by PI3K/Akt signal pathway. Key words: Endothelial progenitor cell; Metabolic Syndrome; Pioglitazone; Adhesion; Phosphatidylinositol 3 kinase/protein kinase B