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
Meindert Palmen, MD, PhD*,
Mat J.A.P. Daemen, MD, PhD ,
Leon J. De Windt, PhD*,
Jodil Willems ,
Willem R.M. Dassen, PhD*,
Sylvia Heeneman, PhD,
Rene Zimmermann, PhD ,
Marc Van Bilsen, PhD and
Pieter A. Doevendans, MD, PhD||,¶,*
* Department of Cardiology
Department of Pathology
Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands
Department of Vascular Genomics, Bad Nauheim, Germany
|| Interuniversity Cardiology Institute Netherlands
¶ Heart Lung Center Utrecht (HLCU), Utrecht, the Netherlands
Manuscript received December 12, 2002;
revised manuscript received March 1, 2004,
accepted May 4, 2004.
* Reprint requests and correspondence: Dr. Pieter. A. Doevendans, Heart and Lung Center Utrecht (HLCU), University Hospital Utrecht, Department of Cardiology (room HP E 03.406), 3584CX Utrecht, The Netherlands (Email: p.doevendans{at}hli.azu.nl).
OBJECTIVES: 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.
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Abbreviations and Acronyms
| | AOF = aortic flow | | DMSO = dimethyl sulfoxide | | dP/dtmax = maximal rate of positive pressure development (in mm Hg/s2) | | dP/dtmin = minimal rate of negative pressure development (in mm Hg2) | | FGF = fibroblast growth factor | | HW/BW = heart weight/body weight | | IPC = ischemic preconditioning | | I/R = ischemia and reperfusion | | LDH = lactic dehydrogenase | | LVDP = left ventricular developed pressure | | LVEDP = left ventricular end diastolic pressure | | LVPdia = diastolic left ventricular pressure | | LVPsys = systolic left ventricular pressure | | MAPK = mitogen-activated protein kinase | | PKC = protein kinase C | | TG = transgenic | | TK = tyrosine kinase | | WT = wild type |
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