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Elevated expression of activated Na+/H+ exchanger protein induces hypertrophy in isolated rat neonatal ventricular cardiomyocytes

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Abstract

The plasma membrane protein the Na+/H+ exchanger isoform1 (NHE1) has been implicated in various cardiac pathologies including ischemia/reperfusion damage to the myocardium and cardiac hypertrophy. Levels of NHE1 protein and activity are elevated in cardiac disease; however, the mechanism by which these factors contribute to the accompanying hypertrophy in the myocardium is still not clear. To investigate the mechanism of NHE1-induced hypertrophy in the myocardium we constructed two adenoviral vectors expressing either wild type NHE1 protein or a constitutively active NHE1 protein. Infection of neonatal rat ventricular cardiomyocytes (NRVM) resulted in elevated expression of both wild type NHE1 or constitutively active NHE1. Only expression of activated NHE1 protein resulted in an increase in cell size and in an increase in protein synthesis in isolated cardiomyocyte cells. The results demonstrate that expression of activated NHE1 promotes cardiac hypertrophy in isolated cardiac cells and that simple elevation of levels of wild type NHE1 protein does not have a significant hypertrophic effect in NRVM. The results suggest that regulation of NHE1 activity is a critical direct effector of the hypertrophic effect induced in the myocardium by the NHE1 protein.

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Abbreviations

HA:

Hemagglutinin

NHE:

Na+/H+ exchanger

NRMVs:

Neonatal rat ventricular cardiomyocytes

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Acknowledgments

This study was supported by the Canadian Institutes of Health Research #MOP-97816. Larry Fliegel is supported by an Alberta Heritage Foundation for Medical Research Senior Scientist award.

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  1. Departments of Biochemistry and Pediatrics, University of Alberta, Edmonton, AB, T6G 2H7, Canada

    Fatima Mraiche & Larry Fliegel

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  1. Fatima Mraiche
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  2. Larry Fliegel
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Correspondence to Larry Fliegel.

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Mraiche, F., Fliegel, L. Elevated expression of activated Na+/H+ exchanger protein induces hypertrophy in isolated rat neonatal ventricular cardiomyocytes. Mol Cell Biochem 358, 179–187 (2011). https://doi.org/10.1007/s11010-011-0933-z

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