Cardiac-specific overexpression of fibroblast growth factor-2 protects against myocardial dysfunction and infarction in a murine model of low-flow ischemia

Preconditioning the heart before an ischemic insult has been shown to protect against contractile dysfunction, arrhythmias, and infarction. Pharmacological studies have suggested that fibroblast growth factor-2 (FGF2) is involved in cardioprotection. However, because of the number of FGFs expressed...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2003-12, Vol.108 (25), p.3140-3148
Main Authors: HOUSE, Stacey L, BOLTE, Craig, MING ZHOU, DOETSCHMAN, Thomas, KLEVITSKY, Raisa, NEWMAN, Gilbert, EL J. SCHULTZ, Jo
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cardiology. Vascular system
Coronary Circulation
Coronary heart disease
Cytoprotection
Female
Fibroblast Growth Factor 2 - genetics
Fibroblast Growth Factor 2 - metabolism
Fibroblast Growth Factor 2 - physiology
Heart
Heart - physiopathology
Humans
Male
Medical sciences
Mice
Mice, Knockout
Mice, Transgenic
Myocardial Contraction
Myocardial Infarction - pathology
Myocardial Reperfusion Injury - metabolism
Myocardial Reperfusion Injury - physiopathology
Myocardium - metabolism
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Summary:Preconditioning the heart before an ischemic insult has been shown to protect against contractile dysfunction, arrhythmias, and infarction. Pharmacological studies have suggested that fibroblast growth factor-2 (FGF2) is involved in cardioprotection. However, because of the number of FGFs expressed in the heart and the promiscuity of FGF ligand-receptor interactions, the specific role of FGF2 during ischemia-reperfusion injury remains unclear. FGF2-deficient (Fgf2 knockout) mice and mice with a cardiac-specific overexpression of all 4 isoforms of human FGF2 (FGF2 transgenic [Tg]) were compared with wild-type mice to test whether endogenous FGF2 elicits cardioprotection. An ex vivo work-performing heart model of ischemia was developed in which murine hearts were subjected to 60 minutes of low-flow ischemia and 120 minutes of reperfusion. Preischemic contractile function was similar among the 3 groups. After ischemia-reperfusion, contractile function of Fgf2 knockout hearts recovered to 27% of its baseline value compared with a 63% recovery in wild-type hearts (P
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.0000105723.91637.1C