title: Increased accumulation of tissue ACE in human atherosclerotic coronary artery disease.
abstract: BACKGROUND
  Angiotensin may play a pathophysiological role in experimental 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, may be an important target.
  
  
  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 nonatherosclerotic arteries, ACE immunoreactivity was found in luminal and adventitial vasa vasorum endothelium. In early- and intermediate-stage atherosclerotic 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 angiotensin II was also detected in these areas. ACE expression in macrophages was further examined by in vitro experiments with a monocytoid cell line. ACE activity was induced threefold after differentiation of the cells into macrophages and was further increased after stimulation with acetylated LDL.
  
  
  CONCLUSIONS
  These observations demonstrate that significant sources of tissue ACE in human atherosclerotic plaques are regions 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 production of local angiotensin that may participate in the pathobiology of coronary artery disease. Plaque ACE probably is an important target of drug action.
authors.affiliation: Division of Cardiovascular Medicine, Stanford University Medical Center, Calif, USA.
authors.forename: F
authors.initials: F
authors.lastname: Diet
authors.forename: R E
authors.initials: RE
authors.lastname: Pratt
authors.forename: G J
authors.initials: GJ
authors.lastname: Berry
authors.forename: N
authors.initials: N
authors.lastname: Momose
authors.forename: G H
authors.initials: GH
authors.lastname: Gibbons
authors.forename: V J
authors.initials: VJ
authors.lastname: Dzau
mesh_terms: D000293:Adolescent; D000328:Adult; D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002449:Cell Aggregation; D002460:Cell Line; D008078:Cholesterol, LDL / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D008078:Cholesterol, LDL; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D013755:Tetradecanoylphorbol Acetate