title: Resveratrol Upregulates Cardiac SDF-1 in Mice with Acute Myocardial Infarction through the Deacetylation of Cardiac p53.
abstract: OBJECTIVE
  We previously demonstrated that resveratrol (RSV) administration causes cardiac stromal cell-derived factor (SDF)-1 upregulation and can enhance the mobilization of stem cells in mice with acute myocardial infarction (AMI). However, the upstream signal transduction involved in SDF-1 regulation in the setting of AMI and RSV administration remains unclear. Because RSV is a sirtuin 1 (SIRT1) activator and SIRT proteins act as deacetylases, we investigated the role of SIRT1 in SDF-1 upregulation and its subsequent effects.
  
  
  RESULTS
  In vitro experiments with H9C2 cardiomyocytes under hypoxia and serum-deprivation conditions showed that p53 acted upstream of SDF-1. RSV could not regulate SDF-1 effectively after SIRT1 silencing, indicating that it is dependent on SIRT1. Subsequently, male C57BL/6 mice were divided into four groups: 1) sham, 2) MI, 3) MI+RSV, and 4) MI+RSV plus nicotinamide, an inhibitor of the deacetylase activity of SIRT (MI+RSV+NAM). Compared with the sham mice, AMI caused a slight increase in the cardiac p53 level and resulted in significant SIRT1 downregulation and p53 acetylation or activation. Compared with the MI mice, MI+RSV administration improved the cardiac SDF-1 level and reversed the reduction of SIRT1 and the activation of p53. Furthermore, we observed less cardiac dysfunction in MI+RSV mice and determined that NAM abolished the effects of RSV.
  
  
  CONCLUSIONS
  RSV enhances cardiac SDF-1 excretion after AMI partially through a SIRT1 normalization/p53 inactivation pathway.
authors.affiliation: Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Hong
authors.affiliation: Department of Clinical Laboratory, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Shimosawa
authors.initials: S
authors.lastname: Tatsuo
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Shou-Dong
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Hou
authors.initials: H
authors.lastname: Jian-Feng
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Jue
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Hai-Yan
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yue-Jin
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005355:Fibrosis; D020868:Gene Silencing / Q000187:drug effects; D006334:Heart Function Tests / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014463:Ultrasonography; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D054377:Chemokine CXCL12; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; D056564:Sirtuin 1; D000077185:Resveratrol