Cardiovascular protection of nonmitogenic human acidic fibroblast growth factor from oxidative damage in vitro and in vivo.

BACKGROUND: In our previous study, a mutant human acidic fibroblast growth factor without mitogenic action (nonmitogenic human acidic fibroblast growth factor) was created, and its protection from the cytotoxic effect of hydrogen peroxide treatment was confirmed in cultured cardiomyocytes. METHODS: The present study was performed to further investigate whether genetically overexpressing nonmitogenic human acidic fibroblast growth factor in cardiomyocytes provides similar protection from the cytotoxic effect of hydrogen peroxide and whether in vivo administration of nonmitogenic human acidic fibroblast growth factor attenuates ischemia/reperfusion-induced cardiac dysfunction and tissue damage and protects the carotid sinus baroreceptor from alcohol-induced damage, as shown by a reduced response of blood pressure to short carotid artery occlusion. RESULTS AND CONCLUSIONS: Cardiomyocytes transfected by nonmitogenic human acidic fibroblast growth factor, with significant increases in the cellular expression and secretion of nonmitogenic human acidic fibroblast growth factor into a culture medium, were resistant to hydrogen-peroxide-induced cytotoxicity, as measured by cell viability. Hearts isolated from rats pretreated with saline, human acidic fibroblast growth factor, or nonmitogenic human acidic fibroblast growth factor for 24 h were subjected to ischemia/reperfusion in the Langendorff system. Ischemia/reperfusion induced cardiac dysfunction in the saline group, but not in the group pretreated with human acidic fibroblast growth factor or nonmitogenic human acidic fibroblast growth factor. Ischemia/reperfusion also caused a release of the cardiac enzyme lactic dehydrogenase into-and an increase in lipid peroxide content in the efflux of-the hearts of saline-treated rats, but not in rats pretreated with human acidic fibroblast growth factor or nonmitogenic human acidic fibroblast growth factor. There was no difference in cardioprotective effects between human acidic fibroblast growth factor and nonmitogenic human acidic fibroblast growth factor. Furthermore, the protective effect of in-vivo-administered nonmitogenic acidic fibroblast growth factor on alcohol-induced damage to the carotid sinus baroreceptor, as shown by the reduced response of blood pressure to short carotid artery occlusion, was also observed. These results suggest that nonmitogenic human acidic fibroblast growth factor, similar to the native human acidic fibroblast growth factor, provides significant cardiovascular protection from oxidative damage in vitro and in vivo.

Protective effects of non-mitogenic human acidic fibroblast growth factor on hydrogen peroxide-induced damage to cardiomyocytes in vitro.

AIM: To study the protective effect of non-mitogenic human acidic fibroblast growth factor (FGF) on cardiac oxidative injury in vivo. METHODS: Ventricular cardiomyocytes were isolated from 1- to 3-d-old neonatal SD mice and cultured in Dulbecco's minimum essential medium supplemented with 15% fetal bovine serum under an atmosphere of 50 mL/L CO2-95% air at 37 degrees, as well as assessed by immunocytochemical assay. We constructed the cardiomyocyte injury model by exposure to a certain concentration of H2O2. Cellular viability, superoxide dismutase (SOD) activity, leakage of maleic dialdehyde and anti-apoptosis effect were included to evaluate the cardiac protective effect of non-mitogenic human acidic FGF. RESULTS: Over 50% of the cardiomyocytes beat spontaneously on the 2nd d of culture and synchronously beat after being cultured for 3 d. Forty-eight hours after plating was completed, the purity of such cultures was 95% myocytes, assessed by an immunocytochemical assay. Cellular viability dramatically decreased with the increasing of the concentration of H2O2. Non-mitogenic human acidic FGF showed significant resistance to the toxic effect of H2O2, significantly increased the cellular viability as well as the activity of SOD, and dramatically decreased the leakage of maleic dialdehyde as well as the cellular apoptosis rate. CONCLUSION: Hydrogen peroxide shows strong cytotoxicity to the cultured cardiac myocytes, and non-mitogenic human acidic FGF shows strong cardio-protective effect when exposed to a certain concentration of H2O2.