{"doi":"10.7554/elife.85571","title":"SIRT2 inhibition protects against cardiac hypertrophy and ischemic injury","abstract":"\n Sirtuins (SIRT) exhibit deacetylation or ADP-ribosyltransferase activity and regulate a wide range of cellular processes in the nucleus, mitochondria, and cytoplasm. The role of the only sirtuin that resides in the cytoplasm, SIRT2, in the development of ischemic injury and cardiac hypertrophy is not known. In this paper, we show that the hearts of mice with deletion of\n Sirt2\n (\n \n Sirt2\n -/-\n \n ) display improved cardiac function after ischemia-reperfusion (I/R) and pressure overload (PO), suggesting that SIRT2 exerts maladaptive effects in the heart in response to stress. Similar results were obtained in mice with cardiomyocyte-specific\n Sirt2\n deletion. Mechanistic studies suggest that SIRT2 modulates cellular levels and activity of nuclear factor (erythroid-derived 2)-like 2 (NRF2), which results in reduced expression of antioxidant proteins. Deletion of\n Nrf2\n in the hearts of\n \n Sirt2\n -/-\n \n mice reversed protection after PO. Finally, treatment of mouse hearts with a specific SIRT2 inhibitor reduced cardiac size and attenuates cardiac hypertrophy in response to PO. These data indicate that SIRT2 has detrimental effects in the heart and plays a role in cardiac response to injury and the progression of cardiac hypertrophy, which makes this protein a unique member of the SIRT family. Additionally, our studies provide a novel approach for treatment of cardiac hypertrophy and injury by targeting SIRT2 pharmacologically, providing a novel avenue for the treatment of these disorders.\n 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and Resveratrol in Medicine","Coenzyme Q10 studies and effects","Biochemical effects in animals","Medicine","Animals","Mice","Cardiomegaly","Ischemia","Myocytes, Cardiac","NF-E2-Related Factor 2","Sirtuin 2"],"mesh_terms":["Animals","Cardiomegaly","Ischemia","Myocytes, Cardiac","NF-E2-Related Factor 2","Mice","Sirtuin 2"],"keywords":["Cardiac hypertrophy","SIRT2","Ischemic injury","Medicine","Ischemia","Sirtuin","Cardiology","Muscle hypertrophy","Biology","Internal medicine","Pharmacology","Genetics","Gene","Mouse","Heart Failure","Sirtuins","QH301-705.5","NF-E2-Related Factor 2","Science","Q","R","Cardiomegaly","Mice","Sirtuin 2","Animals","Myocytes, Cardiac","Biology (General)"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and 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