Increased chymase-dependent angiotensin II formation in human atherosclerotic aorta
Increased chymase-dependent angiotensin II formation in human atherosclerotic aorta
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DOI：
10.1161/01.hyp.33.6.1399
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发表时间：
1999-06-01
期刊：
影响因子：
8.3
通讯作者：
Arakawa, K
中科院分区：
文献类型：
--
作者：
Ihara, M;Urata, H;Arakawa, K
局部形成的血管紧张素II（Ang II）和肥大细胞可能参与动脉粥样硬化的发展。来源于肥大细胞的糜酶是体外人心脏和主动脉中主要的血管紧张素II形成酶。本研究的目的是探讨主动脉血管紧张素II形成活性（AIIFA）和组织化学定位的每一个血管紧张素II形成酶在动脉粥样硬化的人主动脉。正常（n=9），动脉粥样硬化（n=8），和动脉粥样硬化（n=6）人类动脉粥样硬化标本获得尸检或心血管手术从23名受试者（16名男性，7名女性）。测定主动脉标本中的总AIIFA、血管紧张素转换酶（ACE）依赖性AIIFA和糜酶依赖性AIIFA。用免疫细胞化学法检测糜酶和ACE的组织学和细胞定位。动脉粥样硬化和动脉瘤样病变中总AIIFA明显高于正常动脉瘤。在正常人主动脉（82%）和动脉粥样硬化性主动脉（90%）中，大多数AIIFA都是糜酶依赖性的。用抗糜酶、抗类胰蛋白酶或抗ACE抗体对相应的主动脉切片进行免疫细胞化学染色，结果显示，正常和粥样硬化动脉内膜的图尼卡外膜中均可见糜酶阳性肥大细胞，而ACE阳性细胞则位于正常主动脉的内皮细胞和粥样硬化新生内膜的巨噬细胞中。动脉粥样硬化病变中糜蛋白酶和类胰蛋白酶阳性肥大细胞的密度略高于正常动脉粥样硬化，但无显著性差异，动脉粥样硬化病变中活化肥大细胞的数量（18%）显著高于动脉粥样硬化（5%）和正常动脉粥样硬化（1%）。我们的研究结果表明，局部血管紧张素II的形成增加动脉粥样硬化病变和糜酶是主要负责这种增加。糜酶在动脉粥样硬化病变发展中的组织学定位和潜在作用似乎与ACE不同。
Locally formed angiotensin II (Ang II) and mast cells may participate in the development of atherosclerosis. Chymase, which originates from mast cells, is the major Ang II-forming enzyme in the human heart and aorta in vitro. The aim of the present study was to investigate aortic Ang II-forming activity (AIIFA) and the histochemical localization of each Ang II-forming enzyme in the atheromatous human aorta. Specimens of normal (n=9), atherosclerotic (n=8), and aneurysmal (n=6) human aortas were obtained at autopsy or cardiovascular surgery from 23 subjects (16 men, 7 women). The total, angiotensin-converting enzyme (ACE)-dependent, and chymase-dependent AIIFAs in aortic specimens were determined. The histologic and cellular localization of chymase and ACE were determined by immunocytochemistry, Total AIIFA was significantly higher in atherosclerotic and aneurysmal lesions than in normal aortas. Most of AIIFA in the human aorta in vitro was chymase-dependent in both normal (82%) and atherosclerotic aortas (90%). Immunocytochemical staining of the corresponding aortic sections with antichymase, antitryptase or anti-ACE antibodies showed that chymase-positive mast cells were located in the tunica adventitia of normal and atheromatous aortas, whereas ACE-positive cells were localized in endothelial cells of normal aorta and in macrophages of atheromatous neointima. The density of chymase- and tryptase-positive mast cells in the atherosclerotic lesions was slightly but not significantly higher than that in the normal aortas, and the number of activated mast cells in the aneurysmal lesions (18%) was significantly higher than in atherosclerotic (5%) and normal (1%) aortas. Our results suggest that local Ang II formation is increased in atherosclerotic lesions and that chymase is primarily responsible for this increase. The histologic localization and potential roles of chymase in the development of atherosclerotic lesions appear to be different from those of ACE.