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Mitochondrial Disruption in Cardiovascular Diseases

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Mitochondrial Biology and Experimental Therapeutics

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Abstract

Mitochondrial dysfunction is a critical factor in the initiation and progression of heart failure. Impairment of mitochondrial metabolism decreases energy production and leads to enhanced oxidative and calcium mediated injury to the myocardium. Mitochondrial dysfunction leads to progressive contractile dysfunction, ultimately to cardiomyocyte death. Myocardial ischemia and infarction, as well as pressure overload, are external causes of heart failure associated with impaired mitochondrial function. Genetic defects in both nuclear-encoded and mitochondrial DNA-encoded mitochondrial proteins lead to cardiomyopathy and eventual heart failure, highlighting those mitochondrial functions required to support normal cardiac physiology. Maladaptive neurohumoral response(s) to decreased cardiac contractile function activates cardiomyocyte signaling that results in impaired cardiac metabolism. For these reasons, cardiac metabolism in general and mitochondrial function remain novel therapeutic targets. Future treatment approaches include modulation of cardiac substrate selection, biochemical bypass of metabolic defects in mitochondria, and ultimately the manipulation of mitochondrial dynamics to foster the repair or removal of dysfunctional mitochondria, with accompanying biogenesis of fully-functioning mitochondria.

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Authors and Affiliations

  1. Medical Service, McGuire Veterans Affairs Medical Center, Richmond, VA, USA

    Edward J. Lesnefsky

  2. Division of Cardiology, Department of Medicine, Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA

    Edward J. Lesnefsky & Qun Chen

  3. Department of Biological Sciences, Case Western Reserve University, School of Dental Medicine, Cleveland, OH, USA

    Bernard Tandler

  4. Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, OH, USA

    Charles L. Hoppel

  5. Department of Medicine, Case Western Reserve University, School of Medicine, Cleveland, OH, USA

    Charles L. Hoppel

  6. Center for Mitochondrial Disease, Case Western Reserve University, School of Medicine, Cleveland, OH, USA

    Charles L. Hoppel

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  1. Edward J. Lesnefsky
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  2. Qun Chen
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  3. Bernard Tandler
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  4. Charles L. Hoppel
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Correspondence to Charles L. Hoppel .

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  1. CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Paulo J. Oliveira

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Lesnefsky, E.J., Chen, Q., Tandler, B., Hoppel, C.L. (2018). Mitochondrial Disruption in Cardiovascular Diseases. In: Oliveira, P. (eds) Mitochondrial Biology and Experimental Therapeutics. Springer, Cham. https://doi.org/10.1007/978-3-319-73344-9_12

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