Expression of angiotensin II and interleukin 6 in human coronary atherosclerotic plaques - Potential implications for inflammation and plaque instability
Expression of angiotensin II and interleukin 6 in human coronary atherosclerotic plaques - Potential implications for inflammation and plaque instability
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DOI：
10.1161/01.cir.101.12.1372
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发表时间：
2000-03-28
期刊：
影响因子：
37.8
通讯作者：
Drexler, H
中科院分区：
文献类型：
--
作者：
Schieffer, B;Schieffer, E;Drexler, H
背景：具有激活的肾素-血管紧张素系统（RAS）或RAS基因改变的患者发生心肌梗死（MI）的风险增加。血管紧张素转换酶抑制剂可降低心肌梗死的风险，急性冠状动脉综合征与血清白细胞介素6（IL-6）水平升高相关。因此，本研究评估了血管紧张素II（Ang II）在人冠状动脉粥样硬化斑块中的表达及其对冠心病患者IL-6表达的影响。对12例缺血性或扩张型心肌病心脏移植患者冠状动脉进行IL-6检测，在来自不稳定型心绞痛患者（罪犯病变; n=8）的斑块切除术样本中，以及在来自死于MI的患者（n=13）的破裂冠状动脉中。研究了血管紧张素Ⅱ（Ang Ⅱ）刺激后平滑肌细胞和巨噬细胞合成和释放IL-6的情况。在冠状动脉粥样硬化斑块的肩部和不稳定型心绞痛患者的斑块切除组织中观察到ACE、Ang Ⅱ、AT（1）受体和IL-6与CD 68阳性巨噬细胞的共定位。血管紧张素II被确定在接近假定的破裂部位的人冠状动脉在急性心肌梗死。血管紧张素II诱导的合成和释放IL-6后不久，在体外刺激巨噬细胞和大鼠平滑肌cells.Conclusions-血管紧张素II，AT，受体和ACE的表达在人类动脉粥样硬化冠状动脉的战略网站，这表明血管紧张素II主要是由ACE内冠状动脉斑块。Ang II诱导IL-6及其与AT（1）受体和ACE共定位的观察结果与RAS可能促进血管壁内的炎症过程和急性冠状动脉综合征的发展的观点一致。
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 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 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, 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.