© 2000 American Heart Association, Inc.
Cellular Biology |
Transgenic Myocardial Overexpression of Fibroblast Growth Factor-1 Increases Coronary Artery Density and Branching
From the Max-Planck-Institute (B.F., A.B., S.W., S.K., W.S., R.Z.), Department of Experimental Cardiology, Bad Nauheim, Germany; the Institut für Tierzucht und Tierverhalten (G.E., H.N.), Department of Biotechnology, Neustadt, Germany; Medizinische Universität zu Luebeck (W.M.F.), Medizinische Klinik II, Luebeck, Germany; the Cardiovascular Research Institute (P.A.D.), Maastricht, the Netherlands; and Kerckhoff-Clinic (R.Z.), Bad Nauheim, Germany.
Correspondence to Dr René Zimmermann, Max-Planck-Institute, Department of Experimental Cardiology, Benekestrasse 2, 61231 Bad Nauheim, Germany. E-mail r.zimmer{at}kerckhoff.mpg.de
Abstract—Fibroblast growth factor (FGF)-1 plays important roles during myocardial and coronary morphogenesis. FGF-1 is also involved in the physiological response of the adult heart against ischemia, which includes cardiomyocyte protection and vascular growth. In the present study, we have generated transgenic mice with specific myocardial overexpression of the gene. Transgene expression was verified by Northern blot, and increased FGF-1 protein content was assessed by Western blot and immunoconfocal microscopy. Anatomic, histomorphological, and ultrastructural analyses revealed no major morphological or developmental abnormalities of transgenic hearts. Capillary density was unaltered, whereas the density of coronary arteries, especially arterioles, was significantly increased, as was the number of branches of the main coronary arteries. In addition, the coronary flow was significantly enhanced in transgenic mice ex vivo. These differences in the anatomic pattern of the coronary vasculature are established during the second month of postnatal life. The present findings demonstrate an important role of FGF-1 in the differentiation and growth of the coronary system and suggest that it is a key regulatory molecule of the differentiation of the arterial system.
Key Words: fibroblast growth factor-1 • transgenic • hearts • coronary arteries
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