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.


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.
Li
Xiao-Kun
XK
Research Institute for Diabetic Complications, School of Pharmaceutical Sciences, Wenzhou Medical College, Wenzhou, PR China. xiaokunli@163.net
Lin
Zhuo-Feng
ZF
Li
Yan
Y
Hu
Shifeng
S
Tan
Yi
Y
Huang
Zhifeng
Z
Meng
Juan
J
Liang
Li-Ming
LM
Xiao
Jian
J
Qu
Jia
J
Cai
Lu
L
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D002346:Carotid Sinus / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology* / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects
D016220:Fibroblast Growth Factor 1; D000431:Ethanol; D006861:Hydrogen Peroxide