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Low serum IGF-1 is a risk factor for cardiac allograft vasculopathy in cardiac transplant recipients
Seyedhossein Aharinejad1, Mohamed Salama, Susanne Rödler
1Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria. seyedhossein.aharinejad@meduniwien.ac.at
Insights
Low serum concentrations of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) are linked to cardiac allograft vasculopathy (CAV) after heart transplantation. These biomarkers may help identify patients at risk for CAV and suggest potential therapeutic targets.
Area of Science:
- Cardiology
- Immunology
- Biochemistry
Background:
- Cardiac allograft vasculopathy (CAV) affects 43% of heart transplant recipients within 8 years, with limited treatment options.
- The pathogenesis of CAV is not fully understood, impacting long-term survival.
- The role of insulin-like growth factor-1 (IGF-1) in cardiovascular diseases is known, but its specific involvement in CAV remains unclear.
Purpose of the Study:
- To investigate the association between insulin-like growth factor-1 (IGF-1) and cardiac allograft vasculopathy (CAV).
- To determine if IGF-1 and IGF-binding protein-3 (IGFBP-3) levels can serve as biomarkers for CAV development.
- To explore the potential of IGF-1 as a therapeutic agent for preventing CAV.
Main Methods:
- Protein array screening of serum samples from heart transplant recipients with and without CAV.
- Enzyme-linked immunosorbent assay (ELISA) to quantify serum IGF-1 and IGFBP-3 levels in CAV and no-CAV groups.
- Multivariate logistic regression analysis to identify independent risk factors for CAV.
Main Results:
- IGF-1 and IGFBP-3 were differentially expressed in patients with CAV compared to those without (P=0.037 and P<0.0001).
- Serum IGF-1 concentrations were significantly lower in CAV patients (159.7±114 ng/mL) versus no-CAV patients (234.1±136 ng/mL; P=0.02).
- Serum IGFBP-3 concentrations were significantly lower in CAV patients (0.46±0.37 mg/L) versus no-CAV patients (1.03±0.73 mg/L; P=0.04).
- IGF-1 (OR, 0.89; P=0.04) and IGFBP-3 (OR, 0.09; P=0.03) were identified as independent risk factors for CAV.
Conclusions:
- Lower serum concentrations of IGF-1 and IGFBP-3 are associated with the development of CAV.
- Assessing serum IGF-1 and IGFBP-3 levels may aid in identifying heart transplant recipients at risk for CAV.
- IGF-1 may represent a potential therapeutic strategy to protect cardiac allografts from CAV.
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.
