INDUCTION OF ACIDIC FIBROBLAST GROWTH-FACTOR AND FULL-LENGTH PLATELET-DERIVED GROWTH-FACTOR EXPRESSION IN HUMAN CARDIAC ALLOGRAFTS - ANALYSIS BY PCR, IN-SITU HYBRIDIZATION, AND IMMUNOHISTOCHEMISTRY

Background Further understanding of cardiac allograft vasculopathy (CAV) is needed to improve long-term survival after cardiac transplantation. The diffuse hyperplasia of coronary intima characteristic of CAV suggests that growth factors may play a role in the development of CAV. Fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) are potent mitogens for smooth muscle cells (SMCs), and PDGF is an important cofactor in the pathogenesis of native coronary atherosclerosis. Methods and Results Reverse transcriptase/polymerase chain reaction (RT/PCR), in situ hybridization, and immunohistochemistry were used to determine whether transplantation results in increased cardiac expression of acidic (a)FGF, basic (b)FGF, and PDGF-A and -B chains. Sixty-eight myocardial biopsies from 36 heart transplant recipients and 7 normal hearts were analyzed by PCR. aFGF mRNA was present in 54 of 61 allograft biopsies and was not found in any normal heart. In situ hybridization and immunohistochemistry demonstrated diffuse, intense expression of aFGF mRNA and protein in allograft biopsies, predominantly in myocytes and vascular walls. Only scattered aFGF expression was observed in normal hearts, mRNA for the full-length isoform of PDGF-A chain was found in 43 of 61 allograft biopsies and was not detected in any normal heart. In situ hybridization and immunohistochemistry confirmed that full-length PDCF-A chain mRNA and PDGF protein were present in myocytes and vascular walls. Conclusions Expression of aFGF and PDGF-A chain is significantly increased in cardiac allografts. Cardiac myocytes and vascular walls are the predominant sources of aFGF and PDGF. Diffuse expression of these growth factors in cardiac allografts may be important in the pathogenesis of CAV.