Copper regulation of HIF-1 transcriptional activities

HIF-1 regulated VEGF expression were upregulated in reponse to ischemic injury. However, the VEGF mRNA level were increased in the early stage but decreased in the late stage of myocardial infarction. We found that activities of HIF-1 binding to the HRE sites were possiblely responsible for the differential expression of VEGF. The HIF-1 binding activities were regulated by copper. After ischemic injury, copper concentrations were decreased in the infarct myocardium in the late stage of myocardial infarction, which might reduce VEGF expression through insufficient HIF-1 binding to HRE sites. Rhesus monkeys were subjected to LAD ligation to induce myocardial infarction. After 6 hours or 4 weeks, the hearts were collected and the infarct myocardium were separated to detect VEGF expression by qRT-PCR and to measure HIF-1 binding acitivies by ChIP-Seq. Immunohistochestry was applied for HIF-1α detection. Copper concentrations were determined by atomic absorption spectrometry.