Sun Y, Weber K T
Department of Internal Medicine, University of Missouri Health Sciences Center, Columbia, USA.
J Mol Cell Cardiol. 1996 May;28(5):851-8. doi: 10.1006/jmcc.1996.0080.
Following left coronary artery ligation in the rat, markedly increased angiotensin converting enzyme (ACE) binding appears at the site of myocardial infarction (MI). This is also the case in fibrosed visceral pericardium that follows pericardiotomy alone (without MI). Immunohistochemical ACE labeling, using a monoclonal antibody, indicates fibroblast-like calls express ACE at each of these sites of tissue repair. It is unknown, however, whether these cells are phenotypically transformed fibroblasts containing alpha-smooth muscle actin (i.e. myofibroblasts). This study was therefore undertaken to determine whether myofibroblasts appear at the site of MI and pericardial fibrosis and their relationship to ACE expression. MI was created by left coronary artery ligation. Fibrosis of the visceral pericardium was induced by pericardiotomy alone. Hearts were studied on postoperative day 3, week 1, 2, 4 and 8. In serial sections of the same heart: immunohistochemistry (anti alpha-smooth muscle actin antibody and monoclonal ACE antibody, 9B9) was used to detect myofibroblasts and cells expressing ACE, respectively. We found that at sites of MI and pericardial fibrosis, myofibroblasts began to appear on day 3 and became abundant at week 1, 2, 4 and remained in these repairing sites for at least 8 weeks. Myofibroblasts at sites of MI and pericardial fibrosis are positively labeled by ACE antibody. Thus in these models of tissue repair involving either MI or pericardial fibrosis, myofibroblasts are associated with ACE expression. These findings suggest that myofibroblast ACE may play a role in the fibrogenic response of tissue repair in the rat myocardium by regulating local concentrations of substances involved in healing and matrix remodeling.
在大鼠左冠状动脉结扎后，心肌梗死（MI）部位的血管紧张素转换酶（ACE）结合显著增加。仅进行心包切开术（无MI）后的纤维化脏层心包中也出现这种情况。使用单克隆抗体进行免疫组织化学ACE标记表明，成纤维细胞样细胞在这些组织修复部位均表达ACE。然而，尚不清楚这些细胞是否为含有α平滑肌肌动蛋白的表型转化成纤维细胞（即肌成纤维细胞）。因此，本研究旨在确定肌成纤维细胞是否出现在MI和心包纤维化部位及其与ACE表达的关系。通过左冠状动脉结扎造成MI。仅通过心包切开术诱导脏层心包纤维化。在术后第3天、第1周、第2周、第4周和第8周对心脏进行研究。在同一心脏的连续切片中：分别使用免疫组织化学（抗α平滑肌肌动蛋白抗体和单克隆ACE抗体9B9）检测肌成纤维细胞和表达ACE的细胞。我们发现，在MI和心包纤维化部位，肌成纤维细胞在第3天开始出现，在第1周、第2周、第4周变得丰富，并在这些修复部位至少存留8周。MI和心包纤维化部位的肌成纤维细胞被ACE抗体阳性标记。因此，在这些涉及MI或心包纤维化的组织修复模型中，肌成纤维细胞与ACE表达相关。这些发现表明，肌成纤维细胞ACE可能通过调节参与愈合和基质重塑的物质的局部浓度，在大鼠心肌组织修复的纤维化反应中发挥作用。
