OBJECTIVES: The aim of this study was to determine the cellular localization of angiotensin I-converting enzyme (ACE) in the atherosclerotic plaque and its correlation with inflammation and cellular proliferation. BACKGROUND: Angiotensin I-converting enzyme inhibitors reduce the incidence of vascular events; therefore, tissue ACE may play a determinant role in the pathophysiology of the atherosclerotic plaque. METHODS: Histology and immunocytochemistry of de novo coronary plaques retrieved with directional coronary atherectomy from 141 patients were analyzed: 87 with stable angina, 39 with subacute unstable angina, and 15 with acute unstable angina. RESULTS: Compared with stable patients, unstable patients showed more thrombotic lesions (72% vs. 27%, p < 0.0001), smaller areas of fibrous plaque (2.3 +/- 1.2 mm2 vs. 2.8 +/- 1.1 mm2, p = 0.02), higher cellular proliferative score (0.78 +/- 0.9 vs. 0.27 +/- 0.6, p = 0.003), larger content of ACE-stained cells (26.3 +/- 23% vs. 12.6 +/- 15%, p = 0.005) and larger areas of inflammation as identified by CD68 immunostaining (29.5 +/- 22% vs. 20.2 +/- 19%, p = 0.02). A significant linear correlation was found between CD68- and ACE-stained areas (mm2) among unstable patients (r = 0.6, p = 0.0001), but it was absent among stable patients (r = 0.006, p = 0.9). Co-localization of ACE, CD68, and alpha-actin was confirmed by double immunostaining. Patients with Ki-67-positive staining as an index of cell proliferation showed also significantly larger areas of ACE immunoactivity (p = 0.004). CONCLUSIONS: Our data demonstrate ACE immunoactivity in inflammatory and proliferative cells of coronary atherosclerotic plaques. In particular, patients with unstable angina showed larger areas of ACE immunoactive tissue and proliferating cells compared with stable patients. These observations support a role of the enzyme in the pathophysiology of coronary unstable plaques and suggest potentially different effects of ACE inhibitors according to clinical presentation.
OBJECTIVES: The aim of this study was to determine the cellular localization of angiotensin I-converting enzyme (ACE) in the atherosclerotic plaque and its correlation with inflammation and cellular proliferation. BACKGROUND:Angiotensin I-converting enzyme inhibitors reduce the incidence of vascular events; therefore, tissue ACE may play a determinant role in the pathophysiology of the atherosclerotic plaque. METHODS: Histology and immunocytochemistry of de novo coronary plaques retrieved with directional coronary atherectomy from 141 patients were analyzed: 87 with stable angina, 39 with subacute unstable angina, and 15 with acute unstable angina. RESULTS: Compared with stable patients, unstable patients showed more thrombotic lesions (72% vs. 27%, p < 0.0001), smaller areas of fibrous plaque (2.3 +/- 1.2 mm2 vs. 2.8 +/- 1.1 mm2, p = 0.02), higher cellular proliferative score (0.78 +/- 0.9 vs. 0.27 +/- 0.6, p = 0.003), larger content of ACE-stained cells (26.3 +/- 23% vs. 12.6 +/- 15%, p = 0.005) and larger areas of inflammation as identified by CD68 immunostaining (29.5 +/- 22% vs. 20.2 +/- 19%, p = 0.02). A significant linear correlation was found between CD68- and ACE-stained areas (mm2) among unstable patients (r = 0.6, p = 0.0001), but it was absent among stable patients (r = 0.006, p = 0.9). Co-localization of ACE, CD68, and alpha-actin was confirmed by double immunostaining. Patients with Ki-67-positive staining as an index of cell proliferation showed also significantly larger areas of ACE immunoactivity (p = 0.004). CONCLUSIONS: Our data demonstrate ACE immunoactivity in inflammatory and proliferative cells of coronary atherosclerotic plaques. In particular, patients with unstable angina showed larger areas of ACE immunoactive tissue and proliferating cells compared with stable patients. These observations support a role of the enzyme in the pathophysiology of coronary unstable plaques and suggest potentially different effects of ACE inhibitors according to clinical presentation.
Authors: Xiaofeng Chen; Deborah A Howatt; Anju Balakrishnan; Jessica J Moorleghen; Congqing Wu; Lisa A Cassis; Alan Daugherty; Hong Lu Journal: Arterioscler Thromb Vasc Biol Date: 2016-04-07 Impact factor: 8.311
Authors: Yasunori Takata; Joey Liu; Fen Yin; Alan R Collins; Christopher J Lyon; Chih-Hao Lee; Annette R Atkins; Michael Downes; Grant D Barish; Ronald M Evans; Willa A Hsueh; Rajendra K Tangirala Journal: Proc Natl Acad Sci U S A Date: 2008-03-12 Impact factor: 12.779