A Unified Perspective on Copper Deficiency and Cardiomyopathy

Abstract

Dietary copper restriction in rats results in cardiomyopathy. In rats fed copper-restricted diets from weaning for 5 to 8 weeks, a concentric hypertrophy is apparent, whereas postweaning copper restriction does produce cardiomyopathy without apparent hypertrophy. Both sets of circumstances appear to affect the integrity of the basal laminae of cardiac myocytes and capillaries. In rats fed copper-restricted diets from weaning, decreases in cytochrome c oxidase are related not only to copper's role as a coenzyme, but also to a marked decrease in the nuclear encoded subunits of the enzyme complex. Decreased levels of the delta-subunit of ATP synthase have been observed. However, such aberrations in mitochondrial enzymes, as well as morphologic alterations, apparently do not affect cardiac levels of ATP. This review suggests mechanisms of cardiac adaptation and initiation factors leading to cardiac hypertrophy. We present a hypothetical working model explaining the events leading to cardiac failure in the copper-deficient rat heart based on the present body of knowledge, and compare the pathology with other models of cardiomyopathies.

Metallothionein Inhibits Myocardial Apoptosis in Copper-Deficient Mice: Role of Atrial Natriuretic Peptide

“…A great deal of similarity in heart hypertrophy induced by copper deficiency and pressure overload has been observed. Both cause concentric ventricular hypertrophy (Medeiros et al, 1993). The molecular aspects of myocardial remodeling between the two hypertrophied hearts are also similar (Kang et al, 2000).…”

“…Several studies have focused on the effects of copper deficiency on cuproenzymes in the heart and their role in heart hypertrophy (Medeiros et al, 1993;Prohaska, 1990). Three major components have been considered: (1) the antioxidant system, in particular, copper/zinc-dependent superoxide dismutase (Cu, Zn-SOD); (2) connective tissue function and lysyl oxidase; and (3) energy metabolism, as affected by cytochrome-c oxidase (CCO).…”

“…Heart hypertrophy induced by dietary Cu restriction has been shown to be comparable to that induced by pressure overload in many aspects, including morphological, biochemical, and physiological alterations (Medeiros et al, 1993;Prohaska, 1990). Extensive studies have been undertaken to understand the progression of cardiac hypertrophy induced by pressure overload.…”

Thiamin, selenium, and copper levels in patients with idiopathic dilated cardiomyopathy taking diuretics

“…A low copper-content diet also results in cardiomyopathy in rats 18 . The National Research Council in the USA established the safe content of daily copper intake between 1.5 and 3.0 mg/day.…”

“…The exact mechanisms of cellular injury in copper deficiency have not yet been clarified. However, because the superoxide dismutase enzyme activity is reduced with copper deficiency, we can assume that the lesions found in the myocardial basement membrane result from the loss of protection against the free oxygen radicals produced 18 . The treatment with antioxidants of rats with cardiac disease induced by copper deficiency resulted in a reduction in cardiac hypertrophy and milder mitochondrial injury 19 .…”