Erythropoietin decreased myocardial apoptosis and infarct size in wild-type mice subjected to ischemia and reperfusion, an effect that was significantly diminished in eNOS(-/-) mice.
Does erythropoietin prevent cardiomyocyte apoptosis and reduce infarct size via eNOS in mouse models of ischemia/reperfusion?
Erythropoietin protects cardiomyocytes from apoptosis and reduces infarct size following ischemia/reperfusion through an eNOS-dependent mechanism.
OBJECTIVE: Erythropoietin (EPO), a cytokine best known for its ability to increase red blood cell mass, has recently been shown to protect cardiomyocytes from apoptotic cell death. The objective of the present study was to investigate the role of endothelial nitric oxide synthase (eNOS) in the anti-apoptotic effects of EPO in cardiomyocytes. METHODS AND RESULTS: Neonatal mouse ventricular cardiomyocytes were isolated and cultured from wild-type and eNOS(-/-) mice. Treatment with EPO significantly reduced apoptosis induced by norepinephrine (NE) in the wild-type cardiomyocytes. The reduction of apoptosis was associated with significant increases in eNOS expression, phosphorylation and NO production. However, the anti-apoptotic effects of EPO were significantly decreased in wild-type cardiomyocytes treated with L-NAME, which inhibits nitric oxide synthase activity. The results were further confirmed using eNOS(-/-) cardiomyocytes. To investigate the in vivo significance of eNOS in mediating the anti-apoptotic effects of EPO, wild-type and eNOS(-/-) mice were subjected to myocardial ischemia and reperfusion. EPO decreased myocardial apoptosis and infarct size in wild-type mice. However, the protective effects of EPO were significantly diminished in eNOS(-/-) mice. CONCLUSIONS: EPO increases eNOS expression and NO production in cardiomyocytes. The anti-apoptotic effects of EPO in cardiomyocytes are mediated by eNOS-derived NO production.
Burger et al. (Tue,) conducted a other in Myocardial ischemia and reperfusion. Erythropoietin (EPO) vs. Control / eNOS(-/-) mice / L-NAME was evaluated on Apoptosis and infarct size. Erythropoietin decreased myocardial apoptosis and infarct size in wild-type mice subjected to ischemia and reperfusion, an effect that was significantly diminished in eNOS(-/-) mice.