Alteration of the connective tissue network of striated muscle in copper deficient rats

The connective tissue network in striated muscle, consisting principally of collagen is arranged in a three dimensional network and is intimately associated with muscle function. Previous studies have shown that animals maintained on a copper-deficient diet undergo myocardial hypertrophy and exhibit cardiovascular lesions such as ventricular aneurysms that eventually rupture. A deficiency of copper in the diet is known to inhibit lysyl oxidase, a metalloenzyme requiring copper as a cofactor and which is also responsible for collagen and elastin crosslinking. Examination by scanning and transmission electron microscopy of skeletal and cardiac muscle from rats maintained on copper-deficient diets showed both gross and microscopic lesions to the connective tissue network. Immunohistochemical staining by light microscopy with antibodies against lysyl oxidase showed that the enzyme was equally present in both control and experimental animals. Fluorescent staining for antibodies against collagen types I and III showed similar results. From these studies we concluded that the collagen secreted during hypertrophy was not crosslinked by lysyl oxidase due to the absence of the copper cofactor. This resulted in the failure of the connective tissue network to transmit and distribute the increased force associated with myocardial hypertrophy and resulted in myocardial aneurysms.