BACKGROUND: Patients with diabetes are at increased risk of ischemic events. Suv39h1 is a histone methyltransferase that catalyzes the methylation of histone 3 lysine 9, which is associated with the suppression of inflammatory genes in diabetes. However, the role of Suv39h1 in myocardial ischemia/reperfusion (I/R) injury under diabetic condition has not been evaluated. METHODS: To generate diabetic model, male SD rats were fed with 60% fat diet followed by intraperitoneal injection with 40mg/kg streptozotocin. Adenovirus encoding Suv39h1 gene was used for Suv39h1 overexpression. Each rat received injections of adenovirus at five myocardial sites. Three days after gene transfection, each rat was subjected to left main coronary artery occlusion and reperfusion. After 30 min ischemia and reperfusion for 4 h, the rats were euthanized for real-time PCR, Western blot, immunohistochemical staining, and morphometric analysis. RESULTS: Delivery of Ad-Suv39h1 into the hearts of diabetic rats could markedly increase Suv39h1 expression. Up-regulation of Suv39h1 significantly reduced infarct size and tissue damage after I/R injury, which was associated with protection from apoptosis of cardiac myocytes and reduction of inflammatory response. In addition, compared with injury group, Ad-Suv39h1 led to a decreased activity of mitogen-activated protein kinase family and its down-steam transcriptional factor NF-κB. CONCLUSION: Overexpression of Suv39h1 results in the de-activation of proinflammatory pathways and reduced apoptosis and myocardial injury. Therefore, Suv39h1 might represent a novel therapeutic strategy to reduce I/R injury under diabetic condition.
BACKGROUND:Patients with diabetes are at increased risk of ischemic events. Suv39h1 is a histone methyltransferase that catalyzes the methylation of histone 3 lysine 9, which is associated with the suppression of inflammatory genes in diabetes. However, the role of Suv39h1 in myocardial ischemia/reperfusion (I/R) injury under diabetic condition has not been evaluated. METHODS: To generate diabetic model, male SD rats were fed with 60% fat diet followed by intraperitoneal injection with 40mg/kg streptozotocin. Adenovirus encoding Suv39h1 gene was used for Suv39h1 overexpression. Each rat received injections of adenovirus at five myocardial sites. Three days after gene transfection, each rat was subjected to left main coronary artery occlusion and reperfusion. After 30 min ischemia and reperfusion for 4 h, the rats were euthanized for real-time PCR, Western blot, immunohistochemical staining, and morphometric analysis. RESULTS: Delivery of Ad-Suv39h1 into the hearts of diabeticrats could markedly increase Suv39h1 expression. Up-regulation of Suv39h1 significantly reduced infarct size and tissue damage after I/R injury, which was associated with protection from apoptosis of cardiac myocytes and reduction of inflammatory response. In addition, compared with injury group, Ad-Suv39h1 led to a decreased activity of mitogen-activated protein kinase family and its down-steam transcriptional factor NF-κB. CONCLUSION: Overexpression of Suv39h1 results in the de-activation of proinflammatory pathways and reduced apoptosis and myocardial injury. Therefore, Suv39h1 might represent a novel therapeutic strategy to reduce I/R injury under diabetic condition.