Up-regulation of endothelin-B receptors in atherosclerotic human coronary arteries
Up-regulation of endothelin-B receptors in atherosclerotic human coronary arteries
复制标题
DOI：
10.1097/00005344-199601000-00023
复制
发表时间：
1996-01-01
影响因子：
3
通讯作者：
Clozel, JP
中科院分区：
文献类型：
--
作者：
Dagassan, PH;Breu, V;Clozel, JP
已知内皮素A （ET(A)）和内皮素B （ET(B)）受体存在于人类冠状动脉中。然而，它们的绝对和相对数量、功能作用和病理影响是不确定的。本研究的目的是表征内皮素受体介导人冠状动脉收缩，并评估心肌病（CMP）和冠状动脉疾病（CAD）对人组织中内皮素受体的影响。为了比较，猪冠状动脉被平行评估。使用[I-125]ET-1和不同的选择性和非选择性ET(A)-和ET(B)-受体激动剂或拮抗剂进行的竞争结合实验显示，人心肌病心脏冠状动脉中ET(A)和ET(B)受体的相对密度（相对B-max）相似(ET(A) 83%和ET(B) 17%；n = 5)和猪心脏(78% ET(A)和22% ET(B)；N = 5)。与此形成鲜明对比的是，来自人类动脉粥样硬化心脏的冠状动脉中ET(B)受体的相对B-max明显更高(51% ET(A)和49% ET(B)；N = 3)。总受体密度（B-max; fmol/mg protein）在猪（385 +/- 29）冠状动脉中最高，其次是人（253 +/- 41）和CMP（174 +/- 20）冠状动脉。供体心脏冠状动脉ET(A)和ET(B)受体的相对和绝对B-max值与CMP心脏相似。ET-1、ET-3、Sarafotoxin S6c （SRTX S6c）、BQ-123、波生坦（Ro 47-0203）的亲和常数K-D值在不同组织间无显著差异。在来自CMP心脏的人冠状动脉中，ET诱导的收缩似乎仅通过ET(A)受体介导。相比之下，在猪冠状动脉中，ET-1介导的最大作用的20%可归因于ET(B)受体，与结合数据一致。ET(B)受体在CAD组织中的功能作用由于自发性相收缩的发生而无法评估。我们得出结论，ET(B)受体在人类冠状动脉粥样硬化中上调。需要进一步的研究来确定这些受体的病理生理重要性。
Both endothelin-A (ET(A)) and endothelin-B (ET(B)) receptors are known to be present in human coronary arteries. However, their absolute and relative amounts, functional roles, and the influence of pathology are uncertain. The goal of the present study was to characterize endothelin receptors mediating constriction in human coronary arteries and to assess the influence of cardiomyopathy (CMP) and coronary artery disease (CAD) on ET receptors in human tissue. For comparison, porcine coronary arteries were evaluated in parallel. Competition binding experiments using [I-125]ET-1 and different selective and nonselective ET(A)- and ET(B)-receptor agonists or antagonists revealed similar relative densities (relative B-max) of ET(A) and ET(B) receptors in coronary arteries from human cardiomyopathic hearts (83% ET(A) and 17% ET(B); n = 5) and porcine hearts (78% ET(A) and 22% ET(B); n = 5). In marked contrast, the relative B-max of ET(B) receptors were significantly higher in coronary arteries from human atherosclerotic hearts (51% ET(A) and 49% ET(B); n = 3). Total receptor density (B-max; fmol/mg protein) was highest in porcine (385 +/- 29) arteries, followed by human CAD (253 +/- 41) and CMP (174 +/- 20) coronary arteries. The relative and absolute B-max values for ET(A) and ET(B) receptors in coronary arteries from a donor heart were similar to those obtained in CMP hearts. There were no significant differences in affinity constants (K-D) values for ET-1, ET-3, Sarafotoxin S6c (SRTX S6c), BQ-123, and bosentan (Ro 47-0203) between tissues. In human coronary arteries from CMP hearts, ET-induced constriction seemed to be solely mediated via ET(A) receptors. In contrast, in porcine coronary arteries 20% of the maximal effect mediated by ET-1 could be attributed to ET(B) receptors, in agreement with the binding data. The functional role of ET(B) receptors in CAD tissue could not be evaluated because of the occurrence of spontaneous phasic contractions. We conclude that ET(B) receptors are up-regulated in human atherosclerotic coronary arteries. Further studies are needed to determine the pathophysiological importance of these receptors.