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-1α protein expression in cardiomyocytes. Subsequent assays showed that IGFBP-1 suppression decreased HIF-1α expression and inhibited hypoxia-induced apoptosis in cardiomyocytes, which was reversed by HIF-1α overexpression, indicating that HIF-1α is essential to IGFBP-1 function in cellular apoptosis. In addition, we showed that IGFBP-1 regulated HIF-1α stabilization through interacting with VHL. The present findings suggest that IGFBP-1–HIF-1α could be targeted for treating ischemic heart disease.

缺氧在缺血性心脏病中很重要。过量的胰岛素样生长因子结合蛋白-1 (IGFBP-1) 量被认为会损害急性心肌梗塞中的心肌细胞。然而，IGFBP-1 影响心肌细胞的机制仍未明确。本研究表明，缺氧可上调心肌细胞中 IGFBP-1 和 HIF-1α 蛋白的表达。随后的分析表明，IGFBP-1 抑制降低了 HIF-1α 的表达并抑制了缺氧诱导的心肌细胞凋亡，这被 HIF-1α 过表达逆转，表明 HIF-1α 对 IGFBP-1 在细胞凋亡中的功能至关重要。此外，我们表明 IGFBP-1 通过与 VHL 相互作用调节 HIF-1α 的稳定性。目前的研究结果表明，IGFBP-1-HIF-1α 可以靶向治疗缺血性心脏病。