Regulation of vascular smooth-muscle cell growth by angiotensin II.

Abnormal growth of vascular smooth-muscle cells is a characteristic of many cardiovascular diseases. This abnormal growth occurs during hypertension-induced vascular hypertrophy, during the development of an atherosclerotic lesion, and during the development of a restenotic lesion following angioplasty. It is becoming increasingly apparent that among the many factors that may influence vascular structure, angiotensin may play a major role. Angiotensin-converting enzyme (ACE) inhibitors decrease hypertension-induced vascular hypertrophy, and, in many animal models, these inhibitors block the development of atherosclerosis and the development of an injury-induced neointimal lesion. Evidence suggests that the local production of angiotensin via tissue-converting enzyme may play an important role in these growth effects. We have demonstrated in animal models that injured vessels express high levels of ACE. Moreover, we have shown that the ability of an ACE inhibitor to block neointimal development correlates better with its ability to inhibit tissue ACE than with its ability to block circulating ACE. The role of angiotensin in human atherosclerosis is not clear. In an immunohistochemical study of human coronary arteries, we have obtained evidence that ACE is present within the atherosclerotic plaque, associated with regions of macrophage clustering. Moreover, in cell culture, monocytes induced to differentiate into macrophages express high levels of ACE. Treatment of these cells with acetylated low density lipoproteins results in a further increase in ACE expression. These results support the hypothesis that ACE may play a role in the development of atherosclerosis. Further studies, however, are required to precisely define this role.