Lysyl oxidase activity, collagen cross-links and connective tissue ultrastructure in the heart of copper-deficient male rats

Copper deficiency is characterized by multiple connective tissue manifestations, such as skeletal and joint abnormalities, and vascular lesions that lend to aneurysms and aortic rupture. However, rite rupture of the heart observed in cooper-deficient male mts is not fully understood. We demonstrated the effect of copper deficiency on cardiac collagen content and solubility regional differences in cardiac lysyl oxidase activity collagen cross-links, and on the ultrastructural morphology of collagen in the myocardium. Weaned male rats fed copper-deficient or copper-adequate diets were examined. Copper-deficient rats died prematurely of heart rupture at the apex, and those who survived exhibited heart enlargement, decreased cardiac lysyl oxidase activity with increasing heart soluble collagen content. Mature collagen cross-links, as assessed by the concentrations of pyridinoline and deoxypyridinoline, were lower both in the apex and in the right and left ventricles of copper-deficient rats as compared with copper-adequate controls. However, in copper-deficient rats, cross-links levels were significantly lower at the apex than at the left and right ventricles. In addition, severe ultrastructural abnormalities in the size and shape of endo-and epimysium collagen fibers were observed in the apex of copper-deficient rats. Transmission electron microscopy showed giant, spiralled or frayed, and spiny collagen fibers. These findings allow us to postulate that the reduced cardiac lysyl oxidase activity accompanied by altered collagen cross-links and an abnormal connective tissue ultrastructure play a significant role in the manifestation of copper deficiency in the male rat.