Title:Targeting Cardiomyocyte Ca<sup>2+</sup> Homeostasis in Heart Failure
VOLUME: 21 ISSUE: 4
Author(s):Asmund T. Roe, Michael Frisk and William E. Louch
Affiliation:Institute for Experimental Medical Research, Kirkeveien 166, 4.etg. Bygg 7, Oslo University Hospital Ullevål, 0407 Oslo, Norway.
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.
