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Exp Ther Med. 2017 Jul;14(1):771-779. doi: 10.3892/etm.2017.4564. Epub 2017 Jun 8.

Role of angiopoietin-2 in the cardioprotective effect of fibroblast growth factor 21 on ischemia/reperfusion-induced injury in H9c2 cardiomyocytes.

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Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, P.R. China.
Department of Cardiology, Beijing Daxing Hospital, Capital Medical University, Beijing 102600, P.R. China.


Fibroblast growth factor 21 (FGF21) exerts a protective effect in ischemia/reperfusion (I/R)-induced cardiac injury. However, the exact molecular mechanism underlying the FGF21 action remains unclear. The present study aimed to evaluate the role of angiopoietin-2 (Angpt2) in the cardioprotective effect of FGF21. For this purpose, the H9C2 cell line was subjected to simulated I/R or aerobic conditions with or without FGF21 administration. Certain groups were also transfected with Angpt2 small interfering RNA (siRNA). Cell viability, apoptosis rate and cell migration were examined, and the expression levels of Angpt2, glucose transporter 1 (GLUT1) and caspase-3 were measured by quantitative polymerase chain reaction (qPCR) and western blot analyses. The results demonstrated that FGF21 administration suppressed apoptosis and increased the cell migration ability following I/R-induced injury. qPCR and western blot data showed a decreased level of GLUT1 after I/R-induced injury, which was reversed by FGF21 administration. Furthermore, inhibition of Angpt2 expression using siRNA enhanced the cardioprotective effect of FGF21 by upregulation of GLUT1. In conclusion, FGF21 administration protected against I/R-induced injury in cardiomyocytes, and further inhibition of Angpt2 with FGF21 administration induced the expression of GLUT1, which may promote the energy metabolism in cardiomyocytes, consequently resulting in a more efficient cardioprotective effect. These results suggested that FGF21 administration and inhibition of Angpt2 could be a novel therapeutic approach for I/R-induced cardiac injury.


H9c2; angiopoietin-2; apoptosis; fibroblast growth factor 21; myocardial ischemia/reperfusion injury

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