We have previously extracted acidic and basic fibroblast growth factors (FGFs) from the hearts of various species including human hearts and from the isolated heart muscle cells of rats. These growth factors stimulate proliferation of a large variety of cells in culture and can act as differentiation or survival factors. FGFs lack a signal sequence necessary for export from the cell, therefore their mode of stimulatory action is poorly understood. We propose that FGFs might be involved in the """"""""wound response"""""""" which occurs when endothelial cells (EC), smooth muscle cells (SMC), and cardiocytes (C) are isolated from their normal environment, maintained on plastic dishes and exposed to wound factors in serum during culturing. EC and SMC in normal adult organisms do not divide, but when injured during vascular disease and manipulation, both cell types proliferate. When placed in culture, EC and SMC proliferate, but cardiocytes stop dividing shortly after birth and cannot be induced to divide in culture. In heart disease cardiocytes are injured by oxygen deprivation and some die and are replaced by non-muscle cells. We extracted FGFs from all 3 cell types with biochemical buffers, affinity chromatography, radioimmuno assays, growth assays, immunodetection methods with specific antibodies and detection of mRNAs with in situ hybridization. Our results show that cultured EC and SMC contain 5-10 fold more FGFs than freshly isolated cells, they express the surface receptor and translocate FGFs to their nuclei where they could exert direct effects on DNA synthesis without leaving the cell. Cultured cardiocytes contain more than twice the amount of FGFs, when compared to freshly isolated cells, they express the receptor for FGFs and show nuclear calization of FGFs. They respond to added FGFs by increased DNA synthesis, yet they never divide, but become multinucleated. In cardiocytes, FGFs might be involved in hypertrophy or act as differentiation factors.
