Angiotensin converting enzyme and myofibroblasts during tissue repair in the rat heart.
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.
Sun
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Y
Department of Internal Medicine, University of Missouri Health Sciences Center, Columbia, USA.
Weber
K T
KT
D000818:Animals; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000032:analysis*; D010496:Pericardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration
D007703:Peptidyl-Dipeptidase A