Abstract
Improved treatments for heart failure patients will require the development of novel therapeutic strategies that target basal disease mechanisms. Disrupted cardiomyocyte Ca2+ homeostasis is recognized as a major contributor to the heart failure phenotype, as it plays a key role in systolic and diastolic dysfunction, arrhythmogenesis, and hypertrophy and apoptosis signaling. In this review, we outline existing knowledge of the involvement of Ca2+ homeostasis in these deficits, and identify four promising targets for therapeutic intervention: the sarcoplasmic reticulum Ca2+ ATPase, the Na+-Ca2+ exchanger, the ryanodine receptor, and t-tubule structure. We discuss experimental data indicating the applicability of these targets that has led to recent and ongoing clinical trials, and suggest future therapeutic approaches.
Keywords: Cardiac myocytes, calcium homeostasis, heart failure, SR Ca2+ ATPase, Na+/Ca2+ exchanger, ryanodine receptor, t-tubules.
Current Pharmaceutical Design
Title:Targeting Cardiomyocyte Ca2+ Homeostasis in Heart Failure
Volume: 21 Issue: 4
Author(s): Asmund T. Roe, Michael Frisk and William E. Louch
Affiliation:
Keywords: Cardiac myocytes, calcium homeostasis, heart failure, SR Ca2+ ATPase, Na+/Ca2+ exchanger, ryanodine receptor, t-tubules.
Abstract: Improved treatments for heart failure patients will require the development of novel therapeutic strategies that target basal disease mechanisms. Disrupted cardiomyocyte Ca2+ homeostasis is recognized as a major contributor to the heart failure phenotype, as it plays a key role in systolic and diastolic dysfunction, arrhythmogenesis, and hypertrophy and apoptosis signaling. In this review, we outline existing knowledge of the involvement of Ca2+ homeostasis in these deficits, and identify four promising targets for therapeutic intervention: the sarcoplasmic reticulum Ca2+ ATPase, the Na+-Ca2+ exchanger, the ryanodine receptor, and t-tubule structure. We discuss experimental data indicating the applicability of these targets that has led to recent and ongoing clinical trials, and suggest future therapeutic approaches.
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Cite this article as:
Roe T. Asmund, Frisk Michael and Louch E. William, Targeting Cardiomyocyte Ca2+ Homeostasis in Heart Failure, Current Pharmaceutical Design 2015; 21 (4) . https://dx.doi.org/10.2174/138161282104141204124129
DOI https://dx.doi.org/10.2174/138161282104141204124129 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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