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 manif estations, such as skeletal and joint abnormalities, and vascular lesi ons that lend to aneurysms and aortic rupture. However, rite rupture o f the heart observed in cooper-deficient male mts is not fully underst ood. We demonstrated the effect of copper deficiency on cardiac collag en content and solubility regional differences in cardiac lysyl oxidas e 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 pre maturely of heart rupture at the apex, and those who survived exhibite d heart enlargement, decreased cardiac lysyl oxidase activity with inc reasing heart soluble collagen content. Mature collagen cross-links, a s 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. Howev er, in copper-deficient rats, cross-links levels were significantly lo wer at the apex than at the left and right ventricles. In addition, se vere ultrastructural abnormalities in the size and shape of endo-and e pimysium collagen fibers were observed in the apex of copper-deficient rats. Transmission electron microscopy showed giant, spiralled or fra yed, and spiny collagen fibers. These findings allow us to postulate t hat 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 t he male rat.