THE PATHOGENESIS OF LEFT VENTRICULAR STIFFNESSIN CARDIOMYOPATHIES : ULTRASTRUCTURAL AND IMMUNOHISTOCHEMICAL STUDY.

心肌病左心室僵硬的发病机制：超微结构和免疫组织化学研究。

基本信息

批准号：
07670819
负责人：
HAYASHI Tetsuya
金额：
$ 1.28万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

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 … More 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

为了明确心肌病左心室僵硬的病因，我们进行了以下研究：(1)对右心室心内膜心肌活检标本进行胶原I、III、IV亚型分析，并对MMP-1、2的表达进行半定量研究。（分级从 0 到 3+）14 例限制性心肌病 (RCM)，21 例肥厚性心肌病(HCM) 和 23 例扩张型心肌病 (DCM) 通过免疫光和电子显微镜此外，通过酶谱法在 7 例 KCM 和 10 例 DCM 病例中测量 MMP-2 活性，并与在旁路获得的正常对照 (n=5) 进行比较。免疫组织化学显示，RCM 和 HCM 中 III 型胶原显着增加，而 DCM 中 I 型和 IV 型胶原显着增加。在 HCM 和 DCM 中，MMP-1 在胶原原纤维和某些成纤维细胞中呈阳性。随着针对 I 型和 III 型胶原的反应性突出，MMP-1 趋于增加。另一方面，MMP-2 及其相关蛋白。通过酶谱法测量的活性在 DCM 中很突出。(2) 为了阐明心肌细胞、胶原蛋白和弹性纤维的三维结构，我们对 15 个尸检心脏（4 个 RCM，1 个阻塞性心脏）进行了研究。通过扫描电子显微镜对 HCM、3 例 DCM、2 例心肌梗塞、OMI 和 5 例正常心脏（无心脏病）和 3 例手术材料（2 例梗阻性 HCM 和 1 例 OMI）进行了不规则连接的研究。 RCM 中最显着的特征是增厚。肌束膜中少于 5 微米的胶原蛋白束与弹力纤维数量增多，与HCM非常相似。另一方面，DCM和OMI的肌内膜和肌束膜均增厚，但弹力纤维数量较少。，胶原蛋白通常组织成 20 微米厚的束，沿着邻近心肌细胞的纵轴延伸。上述研究结果表明 1) 网状网络增加，这应该是类型。 III型胶原蛋白和弹性元件在RCM和HCM中左心室僵硬的原因中发挥重要作用，2）I型胶原蛋白的增加反映了DCM中的替代性纤维化，3）MMP似乎参与了胶原蛋白合成的级联反应以及心肌病中心脏的重塑。