Role of vascular angiotensin-generating system in atherosclerosis and acute coronary syndrome : Specifoc role of macrophages and smooth muscle cells

血管紧张素转换酶(ACE)抑制剂的心脏保护和血管保护作用已有很好的报道。为了研究肾素-血管紧张素系统在动脉粥样硬化疾病中的作用，我们用人类冠状动脉进行了免疫细胞化学分析，用培养的巨噬细胞进行了分子生物学分析，并对脑梗塞和无症状心肌缺血进行了遗传分析。在高细胞病变和动脉粥样硬化斑块中，血管紧张素II和血管紧张素转换酶在巨噬细胞和血管平滑肌细胞中的表达增强。血管紧张素1型受体(AT1)在破裂处的邻近部分有表达，破裂处由收缩的平滑肌细胞组成。纤维硬化斑块内血管紧张素II和血管紧张素转换酶很少或没有。不稳定型心绞痛患者皮损中血管紧张素转换酶和血管紧张素转换酶表达增强。冠状动脉粥样硬化活动性病变中肾素-血管紧张素系统的激活可能导致…在动脉粥样硬化和急性冠脉综合征的发生发展中起重要作用。此外，血管内膜AT1受体可能参与局部血管收缩，从而触发斑块破裂。研究肾素-血管紧张素系统各组分在单核细胞(人单核细胞白血病细胞系THP-1)和巨噬细胞(加入PMA诱导分化的THP-1)中的表达。在单核细胞中检测到AT1和AT2的表达，在向巨噬细胞分化的过程中AT1和AT2的表达分别增加了6.3和6.5倍。肾素表达和血管紧张素转换酶活性也在分化过程中增强。这些结果提示，巨噬细胞的肾素-血管紧张素系统通过自分泌-旁分泌系统发挥作用。ACE基因的纯合缺失等位基因(DD)与血浆和组织中较高水平的ACE活性有关。我们研究了ACE/DD等位基因与脑梗塞的关系，但与脑出血无关。无症状心肌缺血与血管紧张素转换酶基因多态性无关。需要进一步的研究来阐明这些联系的机制。较少

Cardioprotective and vasculoprotective effects of angiotensin-converting enzyme (ACE) inhibitors are well reported. To investigate the role of the renin-angiotensin system in atherogenic diseases, we performed immunocytochemical analyzes using human coronary arteries, molecularbiological analysis using cultured macrophages, and genetic analyzes of cerebral infarction and silent myocardial ischemia.1. In hypercellular lesion and atheromatous plaque, however, enhanced angiotensin II and ACE expression was found in macrophages and smooth muscle cells. Angiotensin type 1 receptor (AT1) was expressed in the adjacent portion of the cap by the rupture site where consist of contractile smooth muscle cells. Fibrosclerotic plaque showed little or no angiotensin II and ACE within the plaque. Enhanced expression of ACE and angiotensin II were found in culprit lesions of patients with unstable angina. Activation of the renin-angiotensin system in the active lesion of coronary atherosclerosis may pl … More ay an important role in the development of atherosclerosis and acute coronary syndrome. Furthermore, AT1 receptor in the intima may contribute to focal vasoconstriction which triggers plaque rupture.2. The expression of the components of the renin-angiotensin system were investigated in monocytes (THP-1 : a human monocytic leukemia cell line) and macrophages (differentiated THP-1 by adding of PMA). The expression of AT1 and AT2 was detected in monocytes and increased up to 6.3 and 6.5-fold during the differentiation to macrophages. Renin expression and ACE activity were also enhanced during the differentiation. These results suggest that the renin-angiotensin system function via autocrine-paracrine system in macrophages.3. Homozygous deletion allele (DD) of the ACE gene is known to be associated higher levels of plasma and tissue ACE activities. We investigated the ACE/DD allele was associated with cerebral infarction but not with cerebral hemorrhage. Silent myocardial ischemia did not show association with polymorphism of the ACE gene. Further studies are required to clarify the mechanism of these association. Less