Insulin-like growth factor binding protein-1 regulates HIF-1α degradation to inhibit apoptosis in hypoxic cardiomyocytes

Hypoxia is important in ischemic heart disease. Excessive Insulin-like growth factor binding protein-1 (IGFBP-1) amounts are considered to harm cardiomyocytes in acute myocardial infarction. However, the mechanisms by which IGFBP-1 affects cardiomyocytes remain undefined. The present study demonstrated that hypoxia up-regulates IGFBP-1 and HIF-1 alpha protein expression in cardiomyocytes. Subsequent assays showed that IGFBP-1 suppression decreased HIF-1 alpha expression and inhibited hypoxia-induced apoptosis in cardiomyocytes, which was reversed by HIF-1 alpha overexpression, indicating that HIF-1 alpha is essential to IGFBP-1 function in cellular apoptosis. In addition, we showed that IGFBP-1 regulated HIF-1 alpha stabilization through interacting with VHL. The present findings suggest that IGFBP-1-HIF-1 alpha could be targeted for treating ischemic heart disease.