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

Background-Patients with an activated renin-angiotensin system (RAS) or gen etic alterations of the RAS are at increased risk of myocardial infarction (MI). Administration of ACE inhibitors reduces the risk of MI, and acute co ronary syndromes are associated with increased interleukin 6 (IL-6) serum l evels. Accordingly, the present study evaluated the expression of angiotens in IT (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 transpla ntation (n=12), in atherectomy samples from patients with unstable angina ( culprit lesion; n=8), and in ruptured coronary arteries from patients who d ied of MI (n=13). Synthesis and release of IL-6 was investigated in smooth muscle cells and macrophages after Ang II stimulation, Colocalization of AC E, Ang II, AT(1) receptor, and IL-6 with CD68-positive macrophages was obse rved at the shoulder region of coronary atherosclerotic plaques and in athe rectomy tissue of patients with unstable angina. Ang II was identified in c lose proximity to the presumed rupture site of human coronary arteries in a cute MI. Ang II induced synthesis and release of IL-6 shortly after stimula tion in vitro in macrophages and rat smooth muscle cells. Conclusions- Ang II, AT, receptor, and ACE are expressed at strategic sites of human atherosclerotic coronary arteries, suggesting that Ang II is prod uced 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 co nsistent with the notion that the RAS may contribute to inflammatory proces ses within the vascular wall and to the development of acute coronary syndr omes.