Angiotensin-converting enzyme and wound healing in diverse tissues of the rat

Autoradiographic binding density of angiotensin-converting enzyme (ACE), an indirect measure of ACE activity, is markedly increased at sites of fibrous tissue that appear in the injured heart. This includes myocardial infarction (MI) caused by left coronary artery ligation; endocardial fibrosis of the interventricular septum and perivascular fibrosis of intramyocardial coronary arterioles of the right ventricle, each of which appear remote to MI; and pericardial fibrosis after pericardiotomy (without MI). Expressed in fibroblast-like cells found at each site of tissue repair, ACE may be common to tissue repair in the rat heart, irrespective of the etiologic basis of injury. To address this hypothesis and to determine whether this also applies to other tissues (skin and kidney), the present study was undertaken. ACE binding density was measured by quantitative in vitro autoradiography (125I-351A) in injured rat heart, skin, and kidney. Experimental observations included foreign-body fibrosis after placement of silk ligature in skin or myocardium, endomyocardial myocyte necrosis and fibrosis that accompanied isoproterenol administration (1 mg/kg sc x 2 days), and embolic infarction of the kidney as a result of mural thrombus of the left ventricle that appeared after anterior MI. Fibrosis was identified by collagen-specific staining with picrosirius red. Hematoxylin-eosin staining and immunohistochemical labeling with alpha-smooth muscle actin (alpha-SMA) antibody were used to address cell morphology and phenotype, respectively. We found (1) endomyocardial fibrosis 2 weeks after isoproterenol; (2) fibrosis surrounding silk suture in heart and skin 1 week after placement; (3) renal infarction 1 week after left coronary artery ligation; (4) numerous fibroblast-like cells containing alpha-SMA, as well as macrophages, at sites of repair in all tissues studied; and (5) markedly increased ACE binding density at each of these sites. Thus ACE is integral to tissue repair in the heart, skin, and kidney of the rat, irrespective of the etiologic basis of injury. At these sites ACE may serve to regulate local concentrations of substances involved in tissue repair.