Journal
CIRCULATION RESEARCH
Volume 111, Issue 9, Pages 1222-1236Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.112.265660
Keywords
bioenergetics; clinical trial; ischemia; permeability transition pore; reperfusion; therapeutics
Funding
- US National Institutes of Health [HL-071158, GM-087483]
- University of Rochester Clinical Translational Sciences Institute
- National Institutes of Health [5 TL1 RR 24135-5]
- American Heart Association
- Children's Cardiomyopathy Foundation
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Ischemic heart disease is a significant cause of morbidity and mortality in Western society. Although interventions, such as thrombolysis and percutaneous coronary intervention, have proven efficacious in ischemia and reperfusion injury, the underlying pathological process of ischemic heart disease, laboratory studies suggest further protection is possible, and an expansive research effort is aimed at bringing new therapeutic options to the clinic. Mitochondrial dysfunction plays a key role in the pathogenesis of ischemia and reperfusion injury and cardiomyopathy. However, despite promising mitochondria-targeted drugs emerging from the laboratory, very few have successfully completed clinical trials. As such, the mitochondrion is a potential untapped target for new ischemic heart disease and cardiomyopathy therapies. Notably, there are a number of overlapping therapies for both these diseases, and as such novel therapeutic options for one condition may find use in the other. This review summarizes efforts to date in targeting mitochondria for ischemic heart disease and cardiomyopathy therapy and outlines emerging drug targets in this field. (Circ Res. 2012;111:1222-1236.)
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