Alterations of endothelin-converting enzyme expression in early and advanced stages of human coronary atherosclerosis.
Alterations of endothelin-converting enzyme expression in early and advanced stages of human coronary atherosclerosis.
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DOI：
10.3892/ijmm.13.5.649
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发表时间：
2004-05
影响因子：
5.4
通讯作者：
E. Hai;Y. Ikura;T. Naruko;N. Shirai;N. Yoshimi;S. Kayo;Y. Sugama;H. Fujino;M. Ohsawa;K. Tanzawa;T. Yokota;M. Ueda
中科院分区：
文献类型：
--
作者：
E. Hai;Y. Ikura;T. Naruko;N. Shirai;N. Yoshimi;S. Kayo;Y. Sugama;H. Fujino;M. Ohsawa;K. Tanzawa;T. Yokota;M. Ueda
内皮素-1是一种有效的血管收缩剂，对血管平滑肌细胞（SMC）具有促有丝分裂活性。内皮素转换酶（ECE）是内皮素-1加工的最终关键酶。我们研究了ECE在不同疾病阶段的人冠状动脉粥样硬化病变中的免疫定位。对13例有弥漫性内膜增厚的正常冠状动脉和10例有早期或晚期粥样硬化斑块的冠状动脉进行了冰冻切片研究。使用的单克隆抗体针对SMC、巨噬细胞、内皮细胞和ECE。为了鉴定表达ECE的细胞类型，还使用双重免疫染色分析。在正常冠状动脉，ECE免疫反应观察到管腔内皮细胞和中膜平滑肌细胞。早期动脉粥样硬化斑块主要由SMC组成，在管腔内皮细胞和内膜SMC中显示增强的ECE表达。在晚期动脉粥样硬化斑块中，在积聚的巨噬细胞和斑块内微血管的内皮细胞中发现了明显的ECE表达，而管腔内皮细胞对ECE的免疫反应性相对较弱。总之，本研究表明，在斑块内表达ECE的主要细胞类型在人类冠状动脉粥样硬化的早期和晚期阶段之间是不同的。ECE表达增强和可能的内皮素-1生成可能有助于SMC增殖和血管收缩在早期动脉粥样硬化阶段，并可能促进斑块不稳定在先进的动脉粥样硬化阶段。
Endothelin-1 is a potent vasoconstrictor and exhibits a mitogenic activity on vascular smooth muscle cells (SMCs). Endothelin-converting enzyme (ECE) is the final key enzyme of endothelin-1 processing. We studied the immunolocalization of ECE in human coronary atherosclerotic lesions with different disease stages. Frozen sections of normal coronary arteries with diffuse intimal thickening (n=13) and those of coronary arteries with early (n=10) or advanced atherosclerotic plaques (n=13) were studied. Monoclonal antibodies used were directed against SMCs, macrophages, endothelial cells, and ECE. For the identification of cell types that express ECE, double immunostaining analysis was also used. In normal coronary arteries, ECE immunoreactivity was observed in luminal endothelial cells and medial SMCs. Early atherosclerotic plaques, which consisted predominantly of SMCs, showed enhanced ECE expression in luminal endothelial cells and intimal SMCs. In advanced atherosclerotic plaques, distinct ECE expression was found in accumulated macrophages and in endothelial cells of intraplaque microvessels, while luminal endothelial cells showed relatively weak immunoreactivity for ECE. In conclusion, the present study demonstrates that the major cell types expressing ECE within the plaques are different between early and advanced stages of human coronary atherosclerosis. Enhanced ECE expression and possible endothelin-1 generation may contribute to SMC proliferation and vasoconstriction in early atherosclerotic stages, and may promote plaque destabilization in advanced atherosclerotic stages.