Perinatal Phenotype and Hypothyroidism Are Associated with Elevated Levels of 21.5- to 22-kDa Basic Fibroblast Growth Factor in Cardiac Ventricles
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Control of cardiomyocyte growth and differentiation may be exercised, in part, at the level of expression of endogenous growth factors such as bFGF (basic fibroblast growth factor), believed to act locally, in an autocrine or paracrine fashion. Examination of bFGF accumulation by extract fractionation and immunoblotting indicated a 4-fold increase of an 18-kDa bFGF in adult compared to newborn rat heart ventricles. In contrast, a 22-kDa bFGF species, found to be the predominant form in newborn ventricles, displayed a 2.5-fold decrease in extracts from adult (compared to neonatal) ventricles. Since newborn rats are physiologically hypothyroid, the effect of thyroid status on the accumulation of 22-kDa bFGF in the heart was examined. A 21.5- to 22-kDa bFGF showed a 5-fold increase in extracts from hyperthyroid rat heart ventricles, compared to those from euthyroid controls. The 21.5- to 22-kDa bFGF was essentially unaffected by thyroid status in extracts from brain. Our data point to a correlation between immature or differentiated cardiac phenotype and the predominance of 21- to 22.5-kDa or 18-kDa bFGF species, respectively. Elevated levels of 21.5- to 22-kDa bFGF detected in cardiac ventricles in either physiological or experimentally induced hypothyroidism indicates that thyroid hormone may, directly or indirectly, down-regulate accumulation of the higher molecular mass forms of bFGF in the heart.
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