Transplantation of bradykinin-preconditioned human endothelial progenitor cells improves cardiac function via enhanced Akt/eNOS phosphorylation and angiogenesis.
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.
Department of Cardiology, Zhongda Hospital, Medical School of Southeast University 87 Dingjiaqiao, Nanjing, Jiangsu, 210009, China.
Zu-Long
ZL
Sheng
Department of Cardiology, Zhongda Hospital, Medical School of Southeast University 87 Dingjiaqiao, Nanjing, Jiangsu, 210009, China.
Yu-Yu
YY
Yao
Department of Cardiology, Zhongda Hospital, Medical School of Southeast University 87 Dingjiaqiao, Nanjing, Jiangsu, 210009, China.
Ye-Fei
YF
Li
Department of Cardiology, Zhongda Hospital, Medical School of Southeast University 87 Dingjiaqiao, Nanjing, Jiangsu, 210009, China.
Cong
C
Fu
Department of Cardiology, Zhongda Hospital, Medical School of Southeast University 87 Dingjiaqiao, Nanjing, Jiangsu, 210009, China.
Gen-Shan
GS
Ma
Bradykinin; endothelial progenitor cells; myocardial infarction; neovascularization; preconditioning