Expression of angiotensin II and interleukin 6 in human coronary atherosclerotic plaques: potential implications for inflammation and plaque instability

Details

Serval ID
serval:BIB_AB0BD44E5E2C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Expression of angiotensin II and interleukin 6 in human coronary atherosclerotic plaques: potential implications for inflammation and plaque instability
Journal
Circulation
Author(s)
Schieffer  B., Schieffer  E., Hilfiker-Kleiner  D., Hilfiker  A., Kovanen  P. T., Kaartinen  M., Nussberger  J., Harringer  W., Drexler  H.
ISSN
1524-4539 (Electronic)
Publication state
Published
Issued date
03/2000
Volume
101
Number
12
Pages
1372-8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar 28
Abstract
BACKGROUND: Patients with an activated renin-angiotensin system (RAS) or genetic alterations of the RAS are at increased risk of myocardial infarction (MI). Administration of ACE inhibitors reduces the risk of MI, and acute coronary syndromes are associated with increased interleukin 6 (IL-6) serum levels. Accordingly, the present study evaluated the expression of angiotensin II (Ang II) in human coronary atherosclerotic plaques and its influence on IL-6 expression in patients with coronary artery disease. METHODS AND RESULTS: Immunohistochemical colocalization of Ang II, ACE, Ang II type 1 (AT(1)) receptor, and IL-6 was examined in coronary arteries from patients with ischemic or dilated cardiomyopathy undergoing heart transplantation (n=12), in atherectomy samples from patients with unstable angina (culprit lesion; n=8), and in ruptured coronary arteries from patients who died of MI (n=13). Synthesis and release of IL-6 was investigated in smooth muscle cells and macrophages after Ang II stimulation. Colocalization of ACE, Ang II, AT(1) receptor, and IL-6 with CD68-positive macrophages was observed at the shoulder region of coronary atherosclerotic plaques and in atherectomy tissue of patients with unstable angina. Ang II was identified in close proximity to the presumed rupture site of human coronary arteries in acute MI. Ang II induced synthesis and release of IL-6 shortly after stimulation in vitro in macrophages and rat smooth muscle cells. CONCLUSIONS: Ang II, AT(1) receptor, and ACE are expressed at strategic sites of human atherosclerotic coronary arteries, suggesting that Ang II is produced primarily by ACE within coronary plaques. The observation that Ang II induces IL-6 and their colocalization with the AT(1) receptor and ACE is consistent with the notion that the RAS may contribute to inflammatory processes within the vascular wall and to the development of acute coronary syndromes.
Keywords
Angina, Unstable/metabolism Angiotensin II/*analysis Animals Coronary Arteriosclerosis/*metabolism/pathology Coronary Vessels/pathology Humans Immunohistochemistry Interleukin-6/*analysis Rats Receptor, Angiotensin, Type 1 Receptor, Angiotensin, Type 2 Receptors, Angiotensin/analysis Renin-Angiotensin System/physiology
Pubmed
Web of science
Create date
05/03/2008 16:40
Last modification date
20/08/2019 15:15
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