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


CONCLUSIONS
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.
Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria. seyedhossein.aharinejad@meduniwien.ac.at
Seyedhossein
S
Aharinejad
Mohamed
M
Salama
Susanne
S
Rödler
Marek
M
Ehrlich
Andreas
A
Zuckermann
Guenther
G
Laufer
D000328:Adult; D000368:Aged; D003920:Diabetes Mellitus / Q000097:blood; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000502:physiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000209:etiology*
C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I