Journal of molecular and cellular cardiology
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J. Mol. Cell. Cardiol. · Jun 2007
HIF-1alpha induced-VEGF overexpression in bone marrow stem cells protects cardiomyocytes against ischemia.
Hypoxia inducible factor-1alpha (HIF-1alpha) is a proangiogenic transcription factor stabilized and activated under hypoxia. It regulates the expression of numerous target genes, including vascular endothelial growth factor (VEGF) and other cytoprotective proteins. In this study, we hypothesized that bone marrow stem cells (BMSCs) secrete growth factors which protect cardiomyocytes via HIF-1alpha pathway. ⋯ The increase and translocation of HIF-1alpha in BMSCs were completely blocked by 2-methoxyestradiol (2-ME2; 5 mumol), a HIF-1alpha inhibitor. Moreover, the protection of cardiomyocytes by BMSC and VEGF secretion was abolished by neutralizing HIF-1alpha antibody in a concentration dependent manner (200-3200 ng/ml). Bone marrow stem cells protect cardiomyocytes by up-regulation of VEGF via activating HIF-1alpha.