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Molecular Defects in Cardiovascular Disease pp 185–195Cite as

Mechanisms Underlying Development of Cardiomyocyte Hypertrophy via Na–H Exchange Stimulation

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Abstract

Na–H exchange (NHE) is the principal mechanism by which the cardiac cell extrudes protons following the development of intracellular acidosis. Although ten isoforms of NHE have now been identified, cardiac cells possess primarily the ubiquitous NHE-1 subtype. There is now strong evidence that NHE-1 contributes to chronic maladaptive myocardial responses to injury including myocardial remodelling and the antiporter likely contributes to the development of heart failure. Experimental studies using both in vitro approaches as well as animal models of heart failure have consistently demonstrated salutary effects of NHE-1 inhibitors in attenuating hypertrophy in response to various stimuli as well as inhibiting heart failure in a large number of animal models. The beneficial effects of NHE-1 inhibitors reflect direct antiremodelling/antihypertrophic effects on the heart which occur via a number of intracellular processes including diminution of intracellular sodium accumulation, prevention of mitochondrial remodelling and reduction in the calcium-dependent activation of the hypertrophic calcineurin pathway. Taken together, NHE-1 inhibition represents a potentially effective therapeutic approach for the treatment of heart failure.

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Acknowledgements

The work originating from the author’s laboratory has been supported by the Canadian Institutes of Health Research.

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  1. Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada

    Morris Karmazyn

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  1. Morris Karmazyn
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Correspondence to Morris Karmazyn .

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  1. St. Boniface General Hospital, Research Centre, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

  2. Jikei University School of Medicine, Shibuya-ku, Ebisu 3-31-6, Tokyo, 150-0013, Japan

    Makoto Nagano

  3. Czech Republic, Institute of Physiology, Academy of Sciences of the, Videnska 1083, Prague, 142 20, Czech Republic

    Bohuslav Ostadal

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Karmazyn, M. (2011). Mechanisms Underlying Development of Cardiomyocyte Hypertrophy via Na–H Exchange Stimulation. In: Dhalla, N., Nagano, M., Ostadal, B. (eds) Molecular Defects in Cardiovascular Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7130-2_14

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