Cardiac hypertrophy in copper-deficient rats is owing to increased mitochondria

Abstract

Dietary copper depletion results in cardiac hypertrophy and ultrastructural alterations. The objective of this study was to determine the components that contribute to cardiac enlargement. Two groups (n = 4) of male, weaning, Sprague-Dawley rats were fed ad libitum with copper-adequate or copper-deficient diets for five weeks. Cross sectional transmission electron micrographs from both groups were evaluated using image analysis to quantify absolute area occupied by myocyte, mitochondria, myofibril, and other intracellular material. Copper-deficient rats had larger myocytes, increased area of mitochondria, and increased ratio of mitochondria:myofibril as well as mitochondria:myocyte. Copper deficiency did not change the absolute area occupied by myofibrils. These data suggested that increase in the absolute mitochondria area is the major contributory factor to the cardiac hypertrophy in copper deficiency. Under the conditions used, myofibril has minimal role toward contributing to the hypertrophic state. The pathology reported resembles human forms of genetic mitochondrial cardiomyopathies. The copper-deficient rat may be a useful model to investigate the underlying biochemical or molecular responses when peptides of enzymes are deleted.

Alterations in Hypertrophic Gene Expression by Dietary Copper Restriction in Mouse Heart

“…Previous studies have suggested that increased mitochondrial volume is the primary cause of cardiac hypertrophy induced by Cu deficiency (4, 6, 7). Changes in mitochondrial metabolism and structure have also been observed in hypertrophied hearts induced by pressure overload.…”

“…This hypertrophy is predominantly concentric (1, 4, 5), where the ventricular and atrial walls are significantly thickened but lumen volumes are decreased. Moreover, increased mitochondrial volume density, increased ratio of mitochondria to myofibrils, and vacuolated mitochondria with disrupted cristae have been a common observation in the heart of Cu‐deficient animals (4, 6, 7).…”

Dietary iron deficiency induces ventricular dilation, mitochondrial ultrastructural aberrations and cytochrome c release: involvement of nitric oxide synthase and protein tyrosine nitration

“…Increased venous return, decreased peripheral resistance, increased inotropic response to noradrenaline (norepinephrine) and vascular remodelling to a larger arterial diameter have all been demonstrated with iron-deficiency-induced anaemia [5][6][7]; a chronic hypersympathetic state coupled with the haemodynamic changes has been suggested to be essential for cardiac hypertrophy [6]. In contrast, copper-deficiency-induced hypertrophy has been attributed to mitochondrial proliferation [36].…”

Relationship between amyloid deposition and intracellular structural changes in familial amyloidotic polyneuropathy

“…Table 1). The areas containing myofibrils and mitochondria in each randomly selected 180-μm 2 area were measured and statistically analyzed, as described previously [25].…”