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Cardioprotection from ischemia by fibroblast growth factor: role of inducible nitric oxide synthase
P Cuevas1, F Carceller, V Martinez-Coso
1Servicio de Histología, Departamento de Investigación, Hospital Ramón y Cajal, Ctra. de Colmenar, Km. 9.100, 28034-Madrid, Spain. pedro.cuevas@hrc.es
Abstract:
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.
Insights
Acidic fibroblast growth factor (FGF-1) protects the heart from reperfusion injury by improving contractile function and reducing infarct size. FGF-1 also upregulates inducible nitric oxide synthase, suggesting a novel cardioprotective mechanism.
Area of Science:
- Cardiovascular Research
- Molecular Cardiology
- Ischemia-Reperfusion Injury
Background:
- Fibroblast growth factor (FGF) shows protective effects in myocardial reperfusion injury.
- Mechanisms underlying FGF's cardioprotection are not fully understood.
Purpose of the Study:
- To investigate the cardioprotective effects of human recombinant acidic fibroblast growth factor (FGF-1) in a rat model of myocardial reperfusion injury.
- To explore the molecular mechanisms, including inducible nitric oxide synthase (iNOS) expression, involved in FGF-1-mediated cardioprotection.
Main Methods:
- A rat model of myocardial reperfusion injury was established via left coronary artery occlusion and reperfusion.
- Intravenous administration of FGF-1 at the onset of reperfusion.
- Assessment of left ventricular contractile function, histological changes, infarct size, and iNOS expression.
Main Results:
- FGF-1 administration significantly improved left ventricular contractile function (more than doubled compared to vehicle).
- Histological analysis showed better preservation of myocardial tissue in the FGF-1 group.
- FGF-1 treatment significantly reduced normalized infarct size (p <0.01) and increased iNOS expression in the area at risk.
Conclusions:
- Human recombinant FGF-1 demonstrates significant cardioprotective effects against myocardial reperfusion injury in rats.
- FGF-1 enhances myocardial tolerance to ischemia by improving function, reducing infarct size, and upregulating iNOS.
- Findings suggest a novel non-mitogenic role for FGF-1 in cardioprotection, highlighting its clinical potential.