Fibroblast growth factor-1 improves cardiac functional recovery and enhances cell survival after ischemia and reperfusion: a fibroblast growth factor receptor, protein kinase C, and tyrosine kinase-dependent mechanism.
OBJECTIVE
We sought to investigate the role of fibroblast growth factor (FGF)-1 during acute myocardial ischemia and reperfusion.


BACKGROUND
The FGFs display cardioprotective effects during ischemia and reperfusion.


METHODS
We investigated FGF-1-induced cardioprotection during ischemia and reperfusion and the intracellular signaling pathways responsible for these effects in an ex vivo murine setup of myocardial ischemia and reperfusion.


RESULTS
Cardiac-specific human FGF-1 overexpression was associated with enhanced post-ischemic hemodynamic recovery and decreased lactate dehydrogenase release during reperfusion. Inhibition of the FGF receptor, protein kinase C (PKC), and tyrosine kinase (TK) resulted in blockade of FGF-1-induced protective effects on cardiac functional recovery and cell death.


CONCLUSIONS
The overexpression of FGF-1 induces cardioprotection through a pathway that involves the FGF receptor, PKC, and TK.
Palmen
Meindert
M
Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), The Netherlands.
Daemen
Mat J A P
MJ
De Windt
Leon J
LJ
Willems
Jodil
J
Dassen
Willem R M
WR
Heeneman
Sylvia
S
Zimmermann
Rene
R
Van Bilsen
Marc
M
Doevendans
Pieter A
PA
D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000502:physiology*; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism / Q000502:physiology*; D006352:Heart Ventricles / Q000378:metabolism; D006439:Hemodynamics; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D011758:Pyrroles; D017468:Receptors, Fibroblast Growth Factor; C105686:SU 5402; D016220:Fibroblast Growth Factor 1; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C