Abstract 18543: Insulin-Like Growth Factor-1 and Igf-1 Binding Protein-3 Mediate Coronary Artery Vasculopathy in Heart Transplant Recipients
The pathogenesis of cardiac allograft vasculopathy (CAV) in long term survivors after heart transplantation (HTX) remains controversial. Histologically, CAV is characterized by intimal hyperplasia of the coronary arteries. Migration, differentiation and proliferation of progenitor cells appear to be critical in CAV pathogenesis, however, the exact mechanism remains unclear. Recently, it was suggested that insulin-like growth factor-1 (IGF-1) and IGF-1 binding protein-3 (IGFBP-3) might play a pathological role in heart failure and affect the migration and proliferation of progenitor cells in vitro. Peripheral blood samples were obtained from 70 HTX patients and CAV was diagnosed in 35 recipients by coronary artery angiography and intravascular ultrasound. Circulating progenitor cells (CPCs) were then cultured from the blood mononuclear cell fraction and phenotyped by multiparametric flow cytometry. The circulating cytokine profile in CAV patients was determined by protein array, which revealed elevated IGF-1 and IGFBP-3 concentrations in CAV (p<0.02) compared to no-CAV patients. Moreover, CPCs from CAV patients proliferated at a higher rate (p<0.01) compared to those from no-CAV patients. IGF-1 serum concentrations correlated with the number of CPCs in CAV patients (rs=0.49, p<0.03). In vitro treatment of CPCs obtained from no-CAV patients with serum of CAV patients enhanced the proliferative capacity of CPCs (p<0.05). These results indicate that IGF-1 and IGFBP-3 are associated with CAV pathogenesis and could govern CPC proliferation in CAV patients, contributing to intimal hyperplasia. Assessment of IGF-1 and IGFPB-3 could be beneficial in CAV monitoring and their targeting might be beneficial in CAV prevention.
- © 2010 by American Heart Association, Inc.