Cardioprotection from ischemia by fibroblast growth factor: role of inducible nitric oxide synthase.
Growing evidence from both animal experiments and clinical observations indicates that fibroblast growth factor (FGF) plays a protective role in myocardial reperfusion injury. The molecular and cellular mechanisms that lead to this postischemic myocardial protection, however, remain largely unexplored. We studied the cardioprotective effects of human recombinant acidic fibroblast growth factor (aFGF, FGF-1) in a rat model of myocardial reperfusion injury, induced by 20 minutes of left coronary artery occlusion followed by 24 hours of reperfusion. Intravenous FGF-1 administration at the onset of heart reperfusion attenuated both the functional impairment and the histological changes of ischemia/reperfusion injury. FGF-1 increases more than twice the left ventricular contractile function (p <0.005) compared to vehicle-treated rats. As shown by histology, myocardial tissue is better preserved with FGF-1 treatment. The infarct size, normalized for the area at risk, was significantly smaller in the FGF-1 group (p <0.01) than in the vehicle group. Furthermore, FGF-1 administration resulted in expression of inducible nitric oxide synthase (iNOS) in the area at risk. Since increased expression of iNOS could potentiate cardioprotection against myocardial reperfusion injury, our findings support a new non-mitogenic role for FGF and add a clinical interest for this protein in increasing myocardial ischemic tolerance.
Cuevas
P
P
Servicio de Histología, Departamento de Investigación, Hospital Ramón y Cajal, Ctra. de Colmenar, Km. 9.100, 28034-Madrid, Spain. pedro.cuevas@hrc.es
Carceller
F
F
Martinez-Coso
V
V
Cuevas
B
B
Fernandez-Ayerdi
A
A
Reimers
D
D
Asin-Cardiel
E
E
Giménez-Gallego
G
G
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D016220:Fibroblast Growth Factor 1; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006152:Cyclic GMP