restoration of altered microrna expression in the ischemic heart with resveratrol恢复改变微rna表达与白藜芦醇缺血性心脏.pdfVIP

Restoration of Altered MicroRNA Expression in the Ischemic Heart with Resveratrol 1 3 3 2 1 Partha Mukhopadhyay , Subhendu Mukherjee , Kaimul Ahsan , Angshuman Bagchi , Pal Pacher , Dipak K. Das3* 1 Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Bethesda, Maryland, United States of America, 2 Buck Institute for Age Research, Novato, California, United States of America, 3 Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, Connecticut, United States of America Abstract Background: Resveratrol, a constituent of red wine, is important for cardioprotection. MicroRNAs are known regulators for genes involved in resveratrol-mediated cardiac remodeling and the regulatory pathway involving microRNA has not been studied so far. Methods: We explored the cardioprotection by resveratrol in ischemia/reperfusion model of rat and determined cardiac functions. miRNA profile was determined from isolated RNA using quantitative Real-time PCR based array. Systemic analyses of miRNA array and theirs targets were determined using a number of computational approaches. Results: Cardioprotection by resveratrol and its derivative in ischemia/reperfusion [I/R] rat model was examined with miRNA expression profile. Unique expression pattern were found for each sample, particularly with resveratrol [pure compound] and longevinex [commercial resveratrol formulation] pretreated hearts. Longevinex and resveratrol pretreatment modulates the expression pattern of miRNAs close to the control level based on PCA analyses. Differential expression was observed in over 25 miRNAs, some of them, such as miR-21 were previously implicated in cardiac remodeling. The target