title: Myocardial Hypertrophic Preconditioning Attenuates Cardiomyocyte Hypertrophy and Slows Progression to Heart Failure Through Upregulation of S100A8/A9.
abstract: BACKGROUND
  Transient preceding brief ischemia provides potent cardioprotection against subsequent long ischemia, termed ischemic preconditioning. Here, we hypothesized that transient short-term hypertrophic stimulation would induce the expression of hypertrophy regression genes and render the heart resistant to subsequent hypertrophic stress, and slow the progression to heart failure, as well.
  
  
  RESULTS
  Cardiomyocyte hypertrophy was induced in mice by either transverse aortic constriction or an infusion of phenylephrine, and in neonatal rat ventricular cardiomyocytes by norepinephrine exposures. In the preconditioning groups, hypertrophic stimulation was provided for 1 to 7 days and then withdrawn for several days by either aortic debanding or discontinuing phenylephrine or norepinephrine treatment, followed by subsequent reexposure to the hypertrophic stimulus for the same period as in the control group. One or 6 weeks after transverse aortic constriction, the heart weight/body weight ratio was lower in the preconditioning group than in the control group, whereas the lung weight/body weight ratio was significantly decreased 6 weeks after transverse aortic constriction. Similar results were obtained in mice receiving phenylephrine infusion and neonatal rat ventricular cardiomyocytes stimulated with norepinephrine. Both mRNA and protein expression of S100A8 and S100A9 showed significant upregulation after the removal of hypertrophic stimulation and persisted for 6 weeks in response to reimposition of transverse aortic constriction. The treatment with recombinant S100A8/A9 inhibited norepinephrine-induced myocyte hypertrophy and reduced the expression of calcineurin and NFATc3, but the silencing of S100A8/A9 prevented such changes.
  
  
  CONCLUSIONS
  Preconditioning with prohypertrophic factors exerts an antihypertrophic effect and slows the progression of heart failure, indicating the existence of the phenomenon for hypertrophic preconditioning.
authors.affiliation: From Sate Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.W., B.W., J.Z., Z.Z., W.X., S.C., X.H., D.X., J.B., M.K., Y.L.); and Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (M.A., M.K.).
authors.forename: Xuan
authors.initials: X
authors.lastname: Wei
authors.affiliation: From Sate Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.W., B.W., J.Z., Z.Z., W.X., S.C., X.H., D.X., J.B., M.K., Y.L.); and Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (M.A., M.K.).
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.affiliation: From Sate Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.W., B.W., J.Z., Z.Z., W.X., S.C., X.H., D.X., J.B., M.K., Y.L.); and Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (M.A., M.K.).
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: From Sate Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.W., B.W., J.Z., Z.Z., W.X., S.C., X.H., D.X., J.B., M.K., Y.L.); and Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (M.A., M.K.).
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: From Sate Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.W., B.W., J.Z., Z.Z., W.X., S.C., X.H., D.X., J.B., M.K., Y.L.); and Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (M.A., M.K.).
authors.forename: Wanling
authors.initials: W
authors.lastname: Xuan
authors.affiliation: From Sate Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.W., B.W., J.Z., Z.Z., W.X., S.C., X.H., D.X., J.B., M.K., Y.L.); and Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (M.A., M.K.).
authors.forename: Shiping
authors.initials: S
authors.lastname: Cao
authors.affiliation: From Sate Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.W., B.W., J.Z., Z.Z., W.X., S.C., X.H., D.X., J.B., M.K., Y.L.); and Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (M.A., M.K.).
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Huang
authors.affiliation: From Sate Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.W., B.W., J.Z., Z.Z., W.X., S.C., X.H., D.X., J.B., M.K., Y.L.); and Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (M.A., M.K.).
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.affiliation: From Sate Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.W., B.W., J.Z., Z.Z., W.X., S.C., X.H., D.X., J.B., M.K., Y.L.); and Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (M.A., M.K.).
authors.forename: Dingli
authors.initials: D
authors.lastname: Xu
authors.affiliation: From Sate Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.W., B.W., J.Z., Z.Z., W.X., S.C., X.H., D.X., J.B., M.K., Y.L.); and Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (M.A., M.K.).
authors.forename: Jianping
authors.initials: J
authors.lastname: Bin
authors.affiliation: From Sate Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.W., B.W., J.Z., Z.Z., W.X., S.C., X.H., D.X., J.B., M.K., Y.L.); and Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (M.A., M.K.).
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
authors.affiliation: From Sate Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China (X.W., B.W., J.Z., Z.Z., W.X., S.C., X.H., D.X., J.B., M.K., Y.L.); and Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (M.A., M.K.). liao18@msn.com kitakaze@zf6.so-net.ne.jp.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
mesh_terms: D000818:Animals; D001024:Aortic Valve Stenosis / Q000150:complications; D019703:Calcineurin / Q000502:physiology; D040501:Calgranulin A / Q000096:biosynthesis* / Q000235:genetics; D040502:Calgranulin B / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000235:genetics / Q000473:pathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006333:Heart Failure / Q000209:etiology / Q000517:prevention & control*; D006984:Hypertrophy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000473:pathology*; D050778:NFATC Transcription Factors / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D050778:NFATC Transcription Factors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C576329:S100A9 protein, mouse; C445503:transcription factor NF-AT c3; D010656:Phenylephrine; D019703:Calcineurin
keywords: S100A8 protein; S100A9 protein; cardiomegaly; heart failure; myocardial preconditioning
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