Sun Y, Cleutjens J P, Diaz-Arias A A, Weber K T
University of Missouri Health Sciences Center, Columbia 65212.
Cardiovasc Res. 1994 Sep;28(9):1423-32. doi: 10.1093/cvr/28.9.1423.
The aim was to test the hypothesis that cardiac angiotensin converting enzyme (ACE) is related to the accumulation of fibrous tissue in the heart.
A model of tissue repair (pericardiotomy with left coronary artery ligation) was used, together with the following: quantitative in vitro autoradiography (125I-351A) to determine ACE binding density; immunohistochemistry (monoclonal ACE antibody, 9B9) to identify cells expressing ACE; and in situ hybridisation to localise cells expressing type I collagen mRNA. Age and sex matched rats receiving this operative procedure without subsequent infarction (sham operated) served as controls to those with left ventricular myocardial infarction. Serial heart sections obtained from each group at 3 days and at 1, 2, 4, and 8 weeks following operation were examined for morphological evidence of injury and inflammatory cells (haematoxylin/eosin) and fibrillar collagen (picrosirius red).
Following myocardial infarction: (a) on day 3, neutrophils and macrophages were present at the site of infarction, while fibrillar collagen and ACE binding were not increased compared with control; (b) at week 1, fibrillar collagen and ACE binding were present at the site of infarction and became progressively more advanced at 2, 4, and 8 weeks; (c) at week 2, there was increased ACE binding in the right ventricle and interventricular septum, when perivascular fibrosis of intramural coronary arteries and microscopic scars appeared, together with endomyocardial fibrosis of the septum; (d) there was marked ACE binding in the fibrosed visceral pericardium two weeks after operation in both myocardial infarction and sham operated groups; (e) there was type I collagen mRNA expression on postoperative week 1, localised within fibroblasts or fibroblast-like cells found at infarct and fibrous tissue sites in the right ventricle, septum, and pericardium; and (f) ACE-labelled cells included fibroblast-like cells, as well as macrophages and endothelial cells.
Thus in this model of tissue repair, marked ACE binding density is associated with fibrillar collagen formation that appears within and remote to the site of myocardial infarction, including the pericardium. Cardiac ACE, originating from type I collagen producing cells, therefore represents an integral component of fibrous tissue formation in this rat model of tissue injury.
旨在验证心脏血管紧张素转换酶（ACE）与心脏纤维组织积聚相关的假说。
采用组织修复模型（心包切开术并结扎左冠状动脉），同时进行以下操作：定量体外放射自显影（125I-351A）以测定ACE结合密度；免疫组织化学（单克隆ACE抗体，9B9）以识别表达ACE的细胞；原位杂交以定位表达I型胶原mRNA的细胞。年龄和性别匹配的大鼠接受此手术操作但无后续梗死（假手术），作为左心室心肌梗死大鼠的对照。对每组在术后3天以及术后1、2、4和8周获取的连续心脏切片进行检查，以寻找损伤、炎性细胞（苏木精/伊红染色）和纤维状胶原（苦味酸天狼星红染色）的形态学证据。
心肌梗死后：（a）第3天，梗死部位有中性粒细胞和巨噬细胞，但与对照相比，纤维状胶原和ACE结合未增加；（b）第1周，梗死部位出现纤维状胶原和ACE结合，在第2、4和8周逐渐进展；（c）第2周，右心室和室间隔的ACE结合增加，此时壁内冠状动脉周围纤维化和微小瘢痕出现，同时室间隔心内膜纤维化；（d）心肌梗死组和假手术组术后两周，纤维化的心包脏层均有明显的ACE结合；（e）术后第1周有I型胶原mRNA表达，定位于在右心室、室间隔和心包的梗死及纤维组织部位发现的成纤维细胞或成纤维细胞样细胞内；（f）ACE标记的细胞包括成纤维细胞样细胞，以及巨噬细胞和内皮细胞。
因此，在这个组织修复模型中，明显的ACE结合密度与心肌梗死部位及其远处（包括心包）出现纤维状胶原形成相关。源自产生I型胶原细胞的心脏ACE，因此是这个大鼠组织损伤模型中纤维组织形成的一个重要组成部分。
