Overexpression of FGF-2 increases cardiac myocyte viability after injury in isolated mouse hearts.
We generated transgenic (TG) mice overexpressing fibroblast growth factor (FGF)-2 protein (22- to 34-fold) in the heart. Chronic FGF-2 overexpression revealed no significant effect on heart weight-to-body weight ratio or expression of cardiac differentiation markers. There was, however, a significant 20% increase in capillary density. Although there was no change in FGF receptor-1 expression, relative levels of phosphorylated c-Jun NH(2)-terminal kinase and p38 kinase as well as of membrane-associated protein kinase C (PKC)-alpha and total PKC-epsilon were increased in FGF-2-TG mouse hearts. An isolated mouse heart model of ischemia-reperfusion injury was used to assess the potential of increased endogenous FGF-2 for cardioprotection. A significant 34-45% increase in myocyte viability, reflected in a decrease in lactate dehydrogenase released into the perfusate, was observed in FGF-2 overexpressing mice and non-TG mice treated exogenously with FGF-2. In conclusion, FGF-2 overexpression causes augmentation of signal transduction pathways and increased resistance to ischemic injury. Thus, stimulation of endogenous FGF-2 expression offers a potential mechanism to enhance cardioprotection.
Sheikh
F
F
Department of Physiology, University of Manitoba, Winnipeg, Manitoba, R3E 3J7, Canada.
Sontag
D P
DP
Fandrich
R R
RR
Kardami
E
E
Cattini
P A
PA
D000818:Animals; D002196:Capillaries / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003326:Coronary Circulation / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D008822:Mice, Transgenic; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000201:enzymology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D009929:Organ Size; D011493:Protein Kinase C / Q000378:metabolism; D019076:Transgenes / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
D016222:Fibroblast Growth Factor 2; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases