EXPRESSION OF ENDOTHELIN-1 IN THE LUNGS OF PATIENTS WITH PULMONARY-HYPERTENSION
EXPRESSION OF ENDOTHELIN-1 IN THE LUNGS OF PATIENTS WITH PULMONARY-HYPERTENSION
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DOI：
10.1056/nejm199306173282402
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发表时间：
1993-06-17
影响因子：
158.5
通讯作者：
STEWART, DJ
中科院分区：
文献类型：
--
作者：
GIAID, A;YANAGISAWA, M;STEWART, DJ
背景肺动脉高压的特征是血管张力增加或小肺动脉壁中的肌细胞异常增殖。内皮素-1是一种有效的内皮源性血管收缩肽，具有重要的促有丝分裂特性。因此，有人认为，内皮素-1可能有助于肺动脉高压患者肺动脉张力增加或平滑肌增生。我们研究了不同原因的肺动脉高压患者肺内内皮素-1产生的部位和幅度。我们研究了15例正常人、11例肺动脉丛源性肺动脉病（4 ~ 6级）和17例继发性肺动脉高压和肺动脉病（1 ~ 3级）肺组织中内皮素-1样免疫反应性（免疫细胞化学分析）和内皮素-1信使RNA（原位杂交）的分布。在对照组中，内皮素-1样免疫反应在血管内皮细胞中很少见到。在肺动脉高压患者中，内皮素-1样免疫反应性丰富，主要存在于中膜增厚和内膜纤维化的肺动脉内皮细胞中。同样，肺动脉高压患者内皮素-1信使RNA增加，主要表达在内皮素-1样免疫反应位点。在丛源性肺动脉病患者中，内皮素-1样免疫反应强度与肺血管阻力呈强相关性，而在继发性肺动脉高压患者中则无相关性。肺动脉高压与血管内皮细胞中内皮素-1的表达增加有关，这表明内皮素-1的局部产生可能有助于与这种疾病相关的血管异常。
Background. Pulmonary hypertension is characterized by an increase in vascular tone or an abnormal proliferation of muscle cells in the walls of small pulmonary arteries. Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide with important mitogenic properties. It has therefore been suggested that endothelin-1 may contribute to increases in pulmonary arterial tone or smooth-muscle proliferation in patients with pulmonary hypertension. We studied the sites and magnitude of endothelin-1 production in the lungs of patients with various causes of pulmonary hypertension.Methods. We studied the distribution of endothelin-1-like immunoreactivity (by immunocytochemical analysis) and endothelin-1 messenger RNA (by in situ hybridization) in lung specimens from 15 control subjects, 11 patients with plexogenic pulmonary arteriopathy (grades 4 through 6), and 17 patients with secondary pulmonary hypertension and pulmonary arteriopathy of grades 1 through 3.Results. In the controls, endothelin-1-like immunoreactivity was rarely seen in vascular endothelial cells. In the patients with pulmonary hypertension, endothelin-1-like immunoreactivity was abundant, predominantly in endothelial cells of pulmonary arteries with medial thickening and intimal fibrosis. Likewise, endothelin-1 messenger RNA was increased in the patients with pulmonary hypertension and was expressed primarily at sites of endothelin-1-like immunoreactivity. There was a strong correlation between the intensity of endothelin-1-like immunoreactivity and pulmonary vascular resistance in the patients with plexogenic pulmonary arteriopathy, but not in those with secondary pulmonary hypertension.Conclusions. Pulmonary hypertension is associated with the increased expression of endothelin-1 in vascular endothelial cells, suggesting that the local production of endothelin-1 may contribute to the vascular abnormalities associated with this disorder.