Angiotensin-converting enzyme expression in human carotid artery atherosclerosis
Angiotensin-converting enzyme expression in human carotid artery atherosclerosis
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DOI：
10.1161/01.hyp.35.1.353
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发表时间：
2000-01-01
期刊：
影响因子：
8.3
通讯作者：
Ferrario, CM
中科院分区：
文献类型：
--
作者：
Fukuhara, M;Geary, RL;Ferrario, CM
血管紧张素转换酶(ACE)抑制剂可降低动物模型中动脉粥样硬化的进展和人类心肌梗死后的再梗死率。虽然已经报道了肾素-血管紧张素系统的组成部分在人类冠状动脉中的表达，但没有关于它们在颈动脉中存在的数据，颈动脉是动脉粥样硬化斑块的常见部位。接下来的研究试图确定在人类颈动脉粥样硬化性病变中是否可以检测到ACE基因和蛋白。24例完整的颈动脉内膜剥脱术标本取自严重颈动脉闭塞症患者(男17例，女7例，年龄68±1岁)，在30min内固定。颈动脉标本含有晚期Stary V型和VI型病变，应用原位杂交和免疫组织化学相结合的方法对人血管紧张素转换酶基因的表达和蛋白进行了横断面定位。使用细胞类型特异性抗体使血管紧张素转换酶与血管内皮细胞、巨噬细胞或淋巴细胞共定位。血管紧张素转换酶蛋白定位于内膜，而上覆中膜大部分未见血管紧张素转换酶染色。在不太复杂的病变中，血管紧张素转换酶染色较弱，可见散在分布的巨噬细胞簇和颈动脉血管内皮细胞的管腔侧。平滑肌细胞大部分为阴性。血管紧张素转换酶染色随着病变变得更加复杂而增加，在巨噬细胞丰富的区域最为明显。斑块肩部有大量ACE阳性的巨噬细胞泡沫细胞和淋巴细胞。在这些区域，微血管内皮细胞和平滑肌细胞ACE表达均为阳性。然而，无炎性细胞斑块中的微血管仅被微弱染色以检测ACE的表达。血管紧张素转换酶基因的标记反映了蛋白表达的模式，将血管紧张素转换酶基因定位于内膜内的巨噬细胞和微血管。总而言之，动脉粥样硬化改变了颈动脉血管紧张素转换酶的产生，增加了斑块炎症区域的转录和翻译。这些数据提供了另一个重要的机制，即与ACE表达增加相关的炎症可能有助于动脉粥样硬化的进展。
Angiotensin-converting enzyme (ACE) inhibitors reduce the progression of atherosclerosis in animal models and reinfarction rates after myocardial infarction in humans. Although expression of components of the renin-angiotensin system has been reported in human coronary arteries, no data regarding their presence in carotid arteries, a frequent site for the occurrence of atherosclerosis plaques, are available. The following study sought to determine whether ACE mRNA and protein can be detected in human carotid atheromatous lesions. Twenty-four intact endarterectomy specimens were obtained from patients with severe carotid occlusive disease (17 males and 7 females, aged 68+/-1 years) and fixed within 30 minutes. Carotid artery specimens contained advanced Stary type V and VI lesions, and human ACE mRNA expression and protein were localized in cross sections by the combination of in situ hybridization and immunohistochemistry. Cell type-specific antibodies were used to colocalize ACE to smooth muscle cells, endothelial cells, macrophages, or lymphocytes. ACE protein was localized in the intima, whereas the overlying media was largely free of ACE staining. In less complicated lesions, ACE staining was modest and could be visualized in scattered clusters of macrophages and on the luminal side of carotid artery vascular endothelium. Smooth muscle cells were largely negative. ACE staining increased as lesions became more complex and was most prominent in macrophage-rich regions. The shoulder regions of plaques contained numerous ACE-positive macrophage foam cells and lymphocytes. In these areas, microvessels were positive for endothelial cell and smooth muscle cell ACE expression. However, microvessels in plaques free of inflammatory cells were stained only faintly for ACE expression. Labeling for ACE mRNA mirrored the pattern of protein expression, localizing ACE mRNA to macrophages and microvessels within the intima. In conclusion, atherosclerosis alters carotid artery ACE production, increasing transcription and translation within regions of plaque inflammation. These data provide another important mechanism by which inflammation associated with increased ACE expression may contribute to the progression of atherosclerosis.