Advanced dilated cardiomyopathy is characterized by distinct ultrastructural remodeling of the extracellular matrix, including prominent perimysial fibrosis and specific shifts in collagen type localization.
The ultrastructural characteristics of collagen and the localization of collagen types were studied in formalin-fixed autopsied human hearts from patients who died in an advanced stage of dilated cardiomyopathy (DCM). The three-dimensional architecture of collagen fibers was studied by scanning electron microscopy by using the cell-maceration method. The localization of collagen type I-VI was demonstrated immunohistochemically using monoclonal antibodies specific to each collagen following the treatment of specimens with trypsin. In the hearts obtained from control subjects without heart disease, there were no significant differences in the ultrastructure and localization of collagens between the fresh and the formalin-fixed hearts. Therefore, formalin-fixation did not affect the ultrastructure of collagen or the immunoreactivity. In DCM, a dense endomysial weave network consisting of fine fibrils was associated predominantly with collagen type I and III, associated moderately with type VI collagen, but less associated with type IV collagen. Perimysial collagen bundles and collagen strands increased both in number and thickness. The outstanding finding was the presence of giant coiled perimysial fibers measuring about 20-30 microns in diameter. The prominent increase in perimysial fibrosis was closely associated with the accumulation of both type I and type III collagen, and associated moderately with type VI collagen. Interestingly, type V collagen increased in the intracellular matrix of the myocardium in DCM. Type II collagen was not present in either normal or diseased hearts. These structural and immunohistochemical characteristics of collagen may provide insights important to assessing the pathogenesis of the cardiac lesion of DCM.
Yoshikane et al. (Wed,) studied this question.