INCREASED ACCUMULATION OF TISSUE ACE IN HUMAN ATHEROSCLEROTIC CORONARY-ARTERY DISEASE

Background Angiotensin may play a pathophysiological role in experimen tal and human cardiovascular disease. Clinical studies have shown that ACE inhibitors reduce mortality, recurrent myocardial infarction, and ischemic events in patients with left ventricular dysfunction. Animal studies suggest that tissue ACE. particularly within blood vessels, m ay be an important target. Methods and Results To study tissue ACE in human coronary artery disease and to identify potential mechanisms of ACE inhibitor action. we examined ACE expression immunohistochemically in nonatherosclerotic and diseased human coronary arteries. in nonath erosclerotic arteries. ACE immunoreactivity was found in luminal and a dventitial vasa vasorum endothelium In early- and intermediate stage a therosclerotic lesions, ACE was detected prominently in regions of fat -laden macrophages and in association with T lymphocytes. in advanced lesions, ACE immunoreactivity was also localized to the endothelium of the microvasculature throughout the plaques. Immunoreactive angiotens in II was also detected in these areas. ACE expression in macrophages was further examined by in vitro experiments with a monocytoid cell fi ne. ACE activity was induced threefold after differentiation of the ce lls into macrophages and was further increased after stimulation with acetylated LDL. Conclusions These observations demonstrate that signif icant sources of tissue ACE in human atherosclerotic plaques are regio ns of inflammatory cells, especially areas of clustered macrophages as well as microvessel endothelial cells, These results suggest that ACE accumulation within the plaque may contribute to an increased product ion of local angiotensin that may participate in the pathobiology of c oronary artery disease. Plaque ACE probably is an important target of drug action.