Low serum IGF-1 is a risk factor for cardiac allograft vasculopathy in cardiac transplant recipients

摘要

BACKGROUND.: Cardiac allograft vasculopathy (CAV) has an incidence of 43% at 8 years after heart transplantation with extremely limited treatment options and unclear pathogenesis. CAV constitutes a significant complication that limits the long-term survival of heart recipients. Insulin-like growth factor-1 (IGF-1) is associated with different cardiovascular diseases; however, its role in CAV pathogenesis remains unknown. METHODS.: Serum samples of 10 matched recipients with CAV and 10 with no-CAV were initially screened with a protein array. Subsequently, IGF-1- and IGF-binding protein-3 (IGFBP-3) were analyzed using enzyme-linked immunosorbent assay in 44 randomly selected CAV and 50 no-CAV patients at two time points. RESULTS.: The initial screening showed that IGF-1 and IGFBP-3 are differentially expressed in CAV compared with no-CAV patients (P=0.037 and P<0.0001, respectively). Subsequent enzyme-linked immunosorbent assay analyses indicated that serum IGF-1 protein concentrations were significantly lower in CAV patients (159.7±114 ng/mL) as compared with no-CAV patients (234.1±136 ng/mL; P=0.02). Serum IGFBP-3 protein concentrations were significantly lower in CAV (0.46±0.37 mg/L) as compared with no-CAV patients (1.03±0.73 mg/L; P=0.04). Multivariate logistic regression analyses showed that IGF-1 (odds ratio, 0.89; P=0.04) and IGFBP-3 (odds ratio, 0.09; P=0.03) are independent risk factors for CAV. CONCLUSION.: Low IGF-1 and IGFPB-3 serum concentrations are associated with CAV. The assessment of serum IGF-1 and IGFPB-3 might be beneficial in identifying cardiac allograft recipients who are prone to develop CAV. Moreover, IGF-1 might be a useful therapy that could protect cardiac allografts against CAV.