title: Enhanced expression of angiotensin-converting enzyme is associated with progression of coronary atherosclerosis in humans.
abstract: BACKGROUND
  The clinical usefulness of angiotensin converting enzyme (ACE) inhibitors in preventing the recurrence of myocardial infarction has been investigated in large randomized trials. Results from many studies using animal models have suggested that ACE inhibitors have vasculoprotective effects, which may contribute to the prevention of coronary atherosclerosis.
  
  
  OBJECTIVE
  To examine the association between vascular angiotensin generation and the development of coronary atherosclerosis in humans.
  
  
  METHODS
  We used immunocytochemical techniques to examine frozen sections from 44 coronary artery segments from 19 corpses.
  
  
  RESULTS
  Three segments were sites of plaque rupture in patients who had died from acute myocardial infarction. Other specimens of coronary artery segments were characterized histologically to be normal artery segments with diffuse intimal thickening (n = 6), hypercellular lesions composed of smooth muscle cells with or without infiltration of macrophages (n = 11), atheromatous plaque (n = 12), and fibrosclerotic plaque (n = 12). In normal arteries with diffuse intimal thickening, ACE was expressed in endothelial cells. In those with hypercellular lesions and atheromatous plaques, however, enhanced ACE expression was found in macrophages and smooth muscle cells. In contrast, arteries with fibrosclerotic plaques exhibited little or no ACE expression within the plaque. All three ruptured plaques expressed ACE strongly in macrophages accumulated around the attenuated fibrous cap.
  
  
  CONCLUSIONS
  The strong association of enhanced ACE expression with the histologic characteristics of plaques suggests that ACE in hypercellular lesions, atheromatous plaques, and ruptured plaques contributes greatly to the further progression of atherosclerosis via an increase in vascular angiotensin II formation and inactivation of bradykinin.
authors.affiliation: Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohishi
authors.forename: M
authors.initials: M
authors.lastname: Ueda
authors.forename: H
authors.initials: H
authors.lastname: Rakugi
authors.forename: T
authors.initials: T
authors.lastname: Naruko
authors.forename: A
authors.initials: A
authors.lastname: Kojima
authors.forename: A
authors.initials: A
authors.lastname: Okamura
authors.forename: J
authors.initials: J
authors.lastname: Higaki
authors.forename: T
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D003324:Coronary Artery Disease / Q000201:enzymology*; D003331:Coronary Vessels / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*
chemical_list: D007703:Peptidyl-Dipeptidase A