| Research Abstract |
To clarify the etiology of left ventricular stiffness in cardiomyopathies, the following studies were conducted. (1) On the right ventricular endomyocardial biopsy specimens, the subtypes of collage I,III and IV were analyzed ant the expression of MMP-1 and 2 werestudies semiquantitatively (graded from 0 to 3+) in 14 cases of restrictive cardiomyopathy (RCM), 21 of hypetrophic cardiomyopathy (HCM) and 23 of dilated cardiomyopathy (DCM) by immuno-light and electron microscopy. Furthermore, the MMP-2 activity measured by zymography in 7 KCM 10 DCM cases were comparted with the normal control (n=5) obtained at the bypass surgery. Immunohistochemically, type III collagenincreased remarkably in RCM and HCM,whereas type I and IV collagen was prominent in DCM.The immunoreactivity ageinst MMP-1 was positive along collagen fibrils and in some fibroblasts both in HCM and DCM.The MMP-1 tended to increase as the reactivity against type I and III collagen was prominent. On the other hand, the MMP-2
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and its activity measured by zymography were prominent in DCM.(2) To elucidate the three dimensional architecture of cardiocytes, collagen and elastic fibers, fifteen autopsied hearts (4 RCM,1obstructuve HCM,3 DCM,2 myocardial infarction, OMI and 5 normal hearts without cardiacdisease) and 3 surgical materials (2 obstructive HCM and 1OMI) were studied by scanning electron microscopy. In RCM and HCM,the cardiocytes were bizarrely shaped and branching, and were irregularly connected with one another. The most striking features in RCM was the thickened perimysium in which collagen bundles of less than 5 mum formed reticular networks together with an increased amount of elastic fibers, which were very similar to those in HCM.On the other hand, in DCM and OMI,endomysium and perimysium were both thickened but the elastic fibers was small in amount. Furthermore, in the perimysium of DCM and OMI,collagens were often organized into thick bundles up 20 mum which ran along the longitudinal axis of neighboring cardiocytes. The above findings suggest that 1) increased reticular networks, which were supposed to be type III colllagen, and elastic elements play an important role as the cause of left ventricular stiffness in RCM and HCM,2) the increased collagen type I reflects the replacement fibrosis in DCM,and 3) MMP appeared to be involved in a cascade of collagen synthesis and the remodeling of the heart in cardiomyopathies. Less
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