University of Western Ontario
Dept. Physiology and Pharmacology
Myocardial ischemia and reperfusion result in cardiac injury, cardiomyocyte death and persistent ventricular dysfunction. Endothelial nitric oxide synthase (eNOS) is constitutively expressed in the heart and produces low levels of nitric oxide (NO), an important molecule involved in a variety of cellular signaling. Activation of protein kinase B (Akt) increases eNOS expression and activity by phosphorylation of its serine residue 1177. ENOS-derived NO protects cardiomyocytes from apoptosis. It has been shown that ginseng protects the heart from myocardial ischemic injuries. Interestingly, ginseng root aqueous extract has been shown to activate eNOS via the PI3K/Akt-pathway in endothelial cells. However, the role of eNOS in ginseng’s cardiac protection during myocardial ischemia and reperfusion has not been established. The goal of the present study is to investigate the molecular mechanisms by which ginseng protects the ischemic myocardium. We hypothesize that ginseng increases NO production via Akt-eNOS signaling pathway to exert anti-apoptotic effects during myocardial ischemia and reperfusion. To test this hypothesis we will employ both in vitro and in vivo models to induce cardiomyocyte death and myocardial injury. Apoptosis will be induced by anoxia/reoxygenation in cultured neonatal cardiomyocytes from wild-type and eNOS-/- mice. In vivo, wild-type and eNOS-/- mice will be subjected to myocardial ischemia and reperfusion to induce myocardial apoptosis and infarction. The role of ginseng in Akt-eNOS activation leading to cardiac protection and inhibition of cardiomyocyte apoptosis during myocardial ischemia and reperfusion will be studied.
|Platform Technology Group:||Pre-Clinical|
|Research Keywords:||Myocardial ischemia and reperfusion, cardioprotection, nitric oxide, signal transduction, apoptosis, cardiomyocyte culture|
|Personal web page:||http://www.uwo.ca/physpharm/faculty/feng_qingping.html|
|Research Projects:||Cardioprotective effects of ginseng: role of nitric oxide|
|Trainees:||Hoda Moazzen (GS); Jing Tang (PDF); not currently accepting applications|