title: Perspectives on the Role and Relevance of Copper in Cardiac Disease.
abstract: Cardiac hypertrophy as a result of dietary copper deficiency has been studied for 40 plus years and is the subject of this review. While connective tissue anomalies occur, a hallmark pathology is cardiac hypertrophy, increased mitochondrial biogenesis, with disruptive cristae, vacuolization of mitochondria, and deposition of lipid droplets. Electrocardiogram abnormalities have been demonstrated along with biochemical changes especially as it relates to the copper-containing enzyme cytochrome c oxidase. The master controller of mitochondrial biogenesis, PGC1-α expression and protein, along with other proteins and transcriptional factors that play a role are upregulated. Nitric oxide, vascular endothelial growth factor, and cytochrome c oxidase all may enhance the upregulation of mitochondrial biogenesis. Marginal copper intakes reveal similar pathologies in the absence of cardiac hypertrophy. Reversibility of the copper-deficient rat heart with a copper-replete diet has resulted in mixed results, depending on both the animal model used and temporal relationships. New information has revealed that copper supplementation may rescue cardiac hypertrophy induced by pressure overload.
authors.affiliation: Division of Biochemistry and Molecular Biology, School of Graduate Studies, University of Missouri Kansas City, 300F Administrative Center, 5115 Oak Street, Kansas City, MO, 64110-2499, USA. Medeirosd@umkc.edu.
authors.forename: Denis M
authors.initials: DM
authors.lastname: Medeiros
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology; D003300:Copper / Q000172:deficiency* / Q000502:physiology; D004195:Disease Models, Animal; D004562:Electrocardiography; D006331:Heart Diseases / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism*; D051381:Rats
chemical_list: D024101:Mitochondrial Proteins; D003300:Copper
keywords: Cardiac hypertrophy; Copper; Cytochrome c oxidase; Mitochondria; NAD+; Nitric oxide; PGC1-α; VEGF