Sun Y, Weber K T
Department of Internal Medicine, University of Missouri Health Sciences Center, Columbia 65212, USA.
Cardiovasc Res. 1996 Apr;31(4):518-25.
Following left coronary artery ligation, markedly increased angiotensin II (AngII) receptor binding appears at the site of myocardial infarction (MI). This is also true for the fibrosed visceral pericardium in rats following pericardiotomy (with or without MI). Cells expressing AngII receptors at these sites remain unknown. In the present study, we sought to identify cells expressing AngII receptors at these sites of fibrosis in the rat heart during both early and late stages of wound healing.
MI was created by left coronary artery ligation. Sham operation included thoracotomy, pericardiotomy and placement of silk ligature around the left coronary artery without MI. Hearts were collected at postoperative week 1 and 4. In serial sections: autoradiography (125I[Sar1,Ile8]AngII) was used to determine cells expressing AngII receptors; hematoxylin-eosin and alpha smooth muscle actin were used for identification of cell morphology and phenotype, respectively; and picrosirius red for identification of fibrillar collagen.
(1) at week 1, necrotic tissue at the site of MI was surrounded by granulation tissue that included macrophages, alpha smooth muscle actin fibroblast-like cells, or myofibroblasts, fibrillar collagen, and new vessels; (2) at week 4, scar tissue had formed and remaining cells were primarily myofibroblasts; (3) pericardial fibrosis was evident at weeks 1 and 4 and contained myofibroblasts, not macrophages or new vessels; (4) at week 1 and 4 myofibroblasts were the predominant cell expressing high-density AngII receptors at the site of MI, while fibroblasts, macrophages and vessels demonstrated low-density AngII receptor binding; and (5) at weeks 1 and 4, myofibroblasts express high-density AngII receptor binding in pericardial fibrosis.
In a rat model of tissue repair involving either MI or pericardial fibrosis, increased AngII receptor expression is primarily associated with myofibroblasts. This suggests AngII may play a role in mediating the fibrogenic response provided by this wound healing cell at sites of tissue injury in the rat heart.
左冠状动脉结扎后，心肌梗死（MI）部位的血管紧张素II（AngII）受体结合显著增加。在心包切开术（伴或不伴MI）后的大鼠纤维化内脏心包中也是如此。在这些部位表达AngII受体的细胞尚不清楚。在本研究中，我们试图确定在伤口愈合的早期和晚期大鼠心脏中这些纤维化部位表达AngII受体的细胞。
通过左冠状动脉结扎创建MI。假手术包括开胸、心包切开术以及在无MI的情况下在左冠状动脉周围放置丝线结扎。在术后第1周和第4周收集心脏。在连续切片中：使用放射自显影法（125I[Sar1，Ile8]AngII）确定表达AngII受体的细胞；苏木精-伊红和α平滑肌肌动蛋白分别用于识别细胞形态和表型；苦味酸天狼星红用于识别纤维状胶原蛋白。
（1）在第1周，MI部位的坏死组织被肉芽组织包围，肉芽组织包括巨噬细胞、α平滑肌肌动蛋白成纤维细胞样细胞或肌成纤维细胞、纤维状胶原蛋白和新血管；（2）在第4周，瘢痕组织形成，剩余细胞主要是肌成纤维细胞；（3）心包纤维化在第1周和第4周明显，包含肌成纤维细胞，而非巨噬细胞或新血管；（4）在第1周和第4周，肌成纤维细胞是MI部位表达高密度AngII受体的主要细胞，而成纤维细胞、巨噬细胞和血管显示低密度AngII受体结合；（5）在第1周和第4周，肌成纤维细胞在心包纤维化中表达高密度AngII受体结合。
在涉及MI或心包纤维化的大鼠组织修复模型中，AngII受体表达增加主要与肌成纤维细胞有关。这表明AngII可能在介导这种伤口愈合细胞在大鼠心脏组织损伤部位提供的纤维化反应中起作用。
