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Cardiac remodeling and subcellular defects in heart failure due to myocardial infarction and aging

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Abstract

Although several risk factors including hypertension, cardiac hypertrophy, coronary artery disease, and diabetes are known to result in heart failure, elderly subjects are more susceptible to myocardial infarction and more likely to develop heart failure. This article is intended to discuss that cardiac dysfunction in hearts failing due to myocardial infarction and aging is associated with cardiac remodeling and defects in the subcellular organelles such as sarcolemma (SL), sarcoplasmic reticulum (SR), and myofibrils. Despite some differences in the pattern of heart failure due to myocardial infarction and aging with respect to their etiology and sequence of events, evidence has been presented to show that subcellular remodeling plays a critical role in the occurrence of intracellular Ca2+-overload and development of cardiac dysfunction in both types of failing heart. In particular, alterations in gene expression for SL and SR proteins induce Ca2+-handling abnormalities in cardiomyocytes, whereas those for myofibrillar proteins impair the interaction of Ca2+ with myofibrils in hearts failing due to myocardial infarction and aging. In addition, different phosphorylation mechanisms, which regulate the activities of Ca2+-cycling proteins in SL and SR membranes as well as Ca2+-binding proteins in myofibrils, become defective in the failing heart. Accordingly, it is suggested that subcellular remodeling involving defects in Ca2+-handling and Ca2+-binding proteins as well as their regulatory mechanisms is intimately associated with cardiac remodeling and heart failure due to myocardial infarction and aging.

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Acknowledgments

Some of the research quoted in the review was supported by a grant from the Canada Institutes of Health Research. The infrastructure for this work was provided by the St. Boniface Hospital Research Foundation.

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The authors declare no conflicts of interest.

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Authors and Affiliations

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

    Naranjan S. Dhalla, Shashanka Rangi, Andrea P. Babick & Vijayan Elimban

  2. Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, R2H 2A6, Canada

    Naranjan S. Dhalla, Shashanka Rangi, Andrea P. Babick & Vijayan Elimban

  3. Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, MB, R2H 2A6, Canada

    Shelley Zieroth

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  1. Naranjan S. Dhalla
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Correspondence to Naranjan S. Dhalla.

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Dhalla, N.S., Rangi, S., Babick, A.P. et al. Cardiac remodeling and subcellular defects in heart failure due to myocardial infarction and aging. Heart Fail Rev 17, 671–681 (2012). https://doi.org/10.1007/s10741-011-9278-7

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