Increased immunoreactive endothelin-1 in human transplant coronary artery disease.

Increased immunoreactive endothelin-1 in human transplant coronary artery disease.
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人类移植冠状动脉疾病中免疫反应性内皮素-1 增加。

DOI:
10.1161/01.cir.94.9.2096
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发表时间:
1996
期刊:
影响因子:
37.8
通讯作者:
Cannon,PJ
Cannon,PJ
中科院分区:
医学1区
文献类型:
--
作者:
Ravalli,S;Szabolcs,M;Albala,A;Michler,RE;Cannon,PJ

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背景移植冠状动脉疾病(transplantcoronaryarterydisease,TCAD)的发病机制尚不清楚,但它被认为是由免疫和非免疫因素相互作用,导致平滑肌细胞增殖和聚集在扩张的新生内膜中所致。内皮素-1(ET-1)是一种强有力的血管收缩剂,具有促血管平滑肌细胞有丝分裂的特性,最近被证明在天然血管动脉粥样硬化中。本研究采用免疫组织化学方法探讨ET-1在TCAD中的作用。方法和结果采用单标记和双标记免疫组织化学方法,对13例TCAD患者冠状动脉和10例正常冠状动脉中ET-1的免疫反应性和细胞定位进行了评估。免疫染色的强度通过半定量方法测定。13例TCAD患者中有11例(85%)出现弥漫性和强烈的ET-1免疫反应,主要见于肌内膜细胞,少量见于巨噬细胞和内皮细胞。与此相反,正常冠状动脉只有微弱的免疫染色定位于内皮层。TCAD的平均半定量分级显著高于正常动脉(1.8比0.7;P<0.05)。ET-1更常见于富含脂质的动脉粥样硬化病变,而不是脂质贫乏的增生性病变。结论TCAD患者内皮素-1的免疫反应性明显增强,可能是由于移植后刺激性细胞因子和生长因子表达上调所致。结果表明,这种促有丝分裂肽在移植物动脉硬化的发病机制中的作用。
BackgroundThe pathogenesis of transplant coronary artery disease (TCAD) is unknown, but it is thought to derive from an interaction between immune and nonimmune factors, leading to smooth muscle cell proliferation and accumulation in the expanded neointima. Endothelin-1 (ET-1), a potent vasoconstrictor with mitogenic properties for vascular smooth muscle cells, has recently been demonstrated in native vessel atherosclerosis. The present study used immunohistochemistry to investigate the role of ET-1 in TCAD.Methods and ResultsET-1 immunoreactivity and cellular localization were assessed in human coronary arteries with TCAD (n=13) and in normal coronary arteries (n=10) with single- and double-label immunohistochemistry. The intensity of immunostaining was determined by a semiquantitative method. Diffuse and intense ET-1 immunoreactivity was found in 11 of 13 patients with TCAD (85%), mainly in myointimal cells and, in lesser amounts, in macrophages and endothelial cells. In contrast, normal coronary arteries had only faint immunostaining localized to the endothelial layer. Mean semiquantitative grade was significantly higher in TCAD than in normal arteries (1.8 versus 0.7;P<.05). ET-1 was more frequently present in lipid-rich, atheromatous lesions than in lipid-poor, proliferative ones. Intimal neovessels consistently immunostained for ET-1.ConclusionsImmunoreactivity for ET-1 is significantly increased in TCAD, possibly as a result of stimulatory cytokines and growth factors that are upregulated in the posttransplant state. The results suggest a role for this mitogenic peptide in the pathogenesis of graft arteriosclerosis.
选择性阻断内皮素 A 亚型受体可减少饲喂胆固醇的仓鼠的早期动脉粥样硬化。
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