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Circulation. 2015 Apr 28;131(17):1506-17; discussion 1517. doi: 10.1161/CIRCULATIONAHA.114.013789. Epub 2015 Mar 27.

Myocardial Hypertrophic Preconditioning Attenuates Cardiomyocyte Hypertrophy and Slows Progression to Heart Failure Through Upregulation of S100A8/A9.

Author information

1
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.).
2
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.

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.

METHODS AND 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 In the preconditioning groups, hypertrophic stimulation was provided for 1 to 7 days and then withdrawn for several days by either aortic debanding or discontinuing phenylephrine or norepinephrine treatment, followed by subsequent reexposure to the hypertrophic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.

KEYWORDS:

S100A8 protein; S100A9 protein; cardiomegaly; heart failure; myocardial preconditioning

PMID:
25820336
PMCID:
PMC4415966
DOI:
10.1161/CIRCULATIONAHA.114.013789
[Indexed for MEDLINE]
Free PMC Article

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