Trophic Effect of Human Pericardial Fluid on Adult Cardiac Myocytes : Differential Role of Fibroblast Growth Factor-2 and Factors Related to Ventricular Hypertrophy

Abstract

Abstract Pericardial fluid (PF) may contain myocardial growth factors that exert paracrine actions on cardiac myocytes. The aims of this study were (1) to investigate the effects of human PF and serum, collected from patients undergoing cardiac surgery, on the growth of cultured adult rat cardiac myocytes and (2) to relate the growth activity of both fluids to the adaptive changes in overloaded human hearts. Both PF and serum increased the rate of protein synthesis, measured by [ ¹⁴ C]phenylalanine incorporation in adult rat cardiomyocytes (PF, +71.9±8.2% [n=17]; serum, +14.9±6.5% [n=13]; both P <.01 versus control medium). The effects of both PF and serum on cardiomyocyte growth correlated positively with the respective left ventricular (LV) mass. However, the magnitude of change with PF was 3-fold greater than with serum ( P <.01). These trophic effects of PF were mimicked by exogenous basic fibroblast growth factor (FGF2) and inhibited by anti-FGF2 antibodies and transforming growth factor-β (TGF-β), suggesting a relationship to FGF2. In addition, FGF2 concentration in PF was 20 times greater than in serum. On the other hand, the LV mass–dependent trophic effect, present in both fluids, was independent of FGF2 concentration or other factors, such as angiotensin II, atrial natriuretic factor, and TGF-β. These data suggest that FGF2 in human PF is a major determining factor in normal myocyte growth, whereas unidentified LV mass–dependent factor(s), present in both PF and serum, participates in the development of ventricular hypertrophy.