ADULT CARDIOMYOCYTES EXPRESS FUNCTIONAL HIGH-AFFINITY RECEPTORS FOR BASIC FIBROBLAST GROWTH-FACTOR

As a first step in addressing the question of function for basic fibro blast growth factor (bFGF) in the adult myocardium, expression of bFGF receptors by adult rat myocytes was investigated. Cross-linking of I- 125-labeled bFGF to purified sarcolemmal vesicles from adult hearts in dicated specific binding to 90- to 104-kDa proteins, whereas equilibri um binding studies revealed the presence of ''low''-affinity (1 nM) an d ''high''-affinity (115 pM) sites. Adult myocytes were found to expre ss short and long variants of bFGF receptor 1 (FGFR-1, tyrosine kinase ) mRNA. Adult heart overall levels of FGFR-1 mRNA were decreased by ab out one-third of corresponding fetal values. Several lines of evidence indicated that bFGF receptors in adult cardiomyocytes in situ and/or in isolation are functional. Isolated adult myocytes were found to be capable of heparin-resistant internalization of I-125-labeled bFGF, to lose their viability after interaction with bFGF-saporin (a mitotoxin known to kill cells after entry via the bFGF receptor), and to respon d to bFGF by activation of mitogen-activated protein kinase. In additi on, introduction of exogenous bFGF into the myocardium by Langendorff perfusion resulted in stimulation of tyrosine phosphorylation in assoc iation with cardiomyocyte intercalated disks, as assessed by immunoflu orescence. It is concluded that adult cardiomyocytes express functiona lly coupled high-affinity bFGF receptors and that they are capable of a biologic response to bFGF in vivo.