MAB4056 Sigma-AldrichAnti-Angiotensin Converting Enzyme Antibody, clone i2H5

We studied the cellular distribution of angiotensin-converting enzyme (ACE) in the heart related to the cell types involved in left ventricular repair and remodeling before and after myocardial infarction by immunohistochemical techniques using monoclonal and polyclonal antibodies. In noninfarcted myocardium of both human and rat, ACE expression was confined to endothelial cells and subendocardial cell layers of the aortic valve. ACE was prominent in endothelia of small arteries and arterioles, whereas only half the coronary capillaries were immunoreactive and venous vessels were almost completely devoid of the enzyme. In a rat model of myocardial infarction, ACE distribution was determined 1, 3, and 7 days and 2, 3, and 6 weeks after coronary occlusion. Three and 7 days after infarction, endothelial cells of sprouting capillaries and macrophages in the marginal zone of necrosis revealed ACE expression. In both human and rat with the onset of fibrosis, intense staining of the enzyme was found in the marginal zone of the repair tissue. In situ hybridization for collagen type I in the rat revealed that zones with high collagen content had almost no ACE immunoreactivity. Vascular smooth muscle cells and cardiomyocytes revealed no ACE expression throughout the study. We conclude that endothelial cells are the principal source for the expression of ACE after myocardial infarction. The observed induction of ACE with the onset of fibrosis suggests a role of this enzyme that is related to tissue repair and remodeling.

Previous studies suggest that while lung angiotensin converting enzyme (ACE) activity is reduced during chronic hypoxia, inhibitors of ACE attenuate hypoxic pulmonary hypertension. In an attempt to explain this paradox we investigated the possibility that whole lung ACE activity may not reflect local pulmonary vascular ACE expression. The experimental approach combined in vivo hemodynamic studies in control and chronically hypoxic rats, measurement of whole lung ACE activity, and evaluation of local pulmonary vascular ACE expression by in situ hybridization and immunohistochemistry. Total lung ACE activity was reduced to 50% of control activity by 5 d of hypoxia and remained low for the duration of the study. Immunohistochemistry showed a marked reduction of ACE staining in alveolar capillary endothelium. However, an increase in ACE staining was observed in the walls of small newly muscularized pulmonary arteries at the level of alveolar ducts and walls. In situ hybridization studies showed increased signal for ACE mRNA in the same vessels. Inhibition of ACE by captopril during chronic hypoxia attenuated pulmonary hypertension and markedly reduced distal muscularization of small pulmonary arteries. In addition, we demonstrated marked longitudinal variation in ACE expression along the normal pulmonary vasculature with the highest levels found in small muscular arteries associated with terminal and respiratory bronchioles. We conclude that local ACE expression is increased in the walls of small pulmonary arteries during the development of hypoxic pulmonary hypertension, despite a generalized reduction in alveolar capillary ACE expression, and we speculate that local arteriolar ACE may play a role in the vascular remodeling associated with pulmonary hypertension.

The localization of angiotensin-converting enzyme (ACE) in human tissues has been studied by the PAP-method with the use of monoclonal antibody 9 B9 against human lung ACE. The enzyme was detected on the surface of endothelial cells in lung, myocardium, liver, intestine and testis as well as in the epithelial cells of the kidney proximal tubules and intestine. The monoclonal antibody 9 B9 did not react with ACE in the epithelial cells of the testis seminiferous tubules. These data suggest that the antibody 9 B9 recognizes epitope which is shared by the ACE molecule of endothelial cells and renal and intestinal epithelial cells but is not present in testicular ACE, or is not accessible there to the antibody.