Dashwood M R, Timm M, Muddle J R, Ong A C, Tippins J R, Parker R, McManus D, Murday A J, Madden B P, Kaski J C
Department of Physiology, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Endothelium. 1998;6(1):61-70. doi: 10.3109/10623329809053405.
Endothelin-1 is a potent vasoconstrictor peptide and mitogen for vascular smooth muscle cells. Increased plasma or tissue levels of endothelin-1 have been described after myocardial infarction and in atherosclerosis, suggesting that this peptide may play a pathophysiological role in various coronary syndromes. Here, we have studied regional variations in ET-1 and its receptors in control and atherosclerotic human coronary vasculature using standard immunohistochemistry and in vitro autoradiography. ET-1 immunoreactivity was associated with luminal endothelial cells and smooth muscle cells at regions of atherosclerosis. ET(A) receptors were present on smooth muscle cells of coronary arteries and on cardiac myocytes. Medial ET(B) receptor binding at the proximal region of coronary arteries was weak, but increased significantly towards distal regions of this vessel (p<0.005 in control and p<0.0005 in ischaemic heart disease). Microvascular endothelial cells in the adventitia of coronary arteries, myocardial microvessels and the endocardial endothelium expressed the ET(B) receptor exclusively. The receptor variations revealed in this study provide supporting evidence that ET-1 is associated with (1) vascular smooth muscle and endothelial cell proliferation, including areas of intimal hyperplasia and regions of neovascularization (2) increased ET-1-induced reactivity of distal portions of the human coronary artery, (3) ET-1-mediated constriction of myocardial microvessels. These results provide new insights into different potential roles for this peptide in healthy and diseased human coronary vasculature.
内皮素-1是一种强效的血管收缩肽，也是血管平滑肌细胞的促有丝分裂原。心肌梗死后及动脉粥样硬化患者体内，血浆或组织中的内皮素-1水平会升高，这表明该肽可能在各种冠状动脉综合征中发挥病理生理作用。在此，我们采用标准免疫组织化学和体外放射自显影技术，研究了对照人群和动脉粥样硬化患者的人类冠状动脉血管中内皮素-1及其受体的区域差异。在动脉粥样硬化区域，内皮素-1免疫反应性与管腔内的内皮细胞和平滑肌细胞相关。内皮素A受体存在于冠状动脉的平滑肌细胞和心肌细胞上。冠状动脉近端区域的中膜内皮素B受体结合较弱，但在该血管的远端区域显著增加（对照组p<0.005，缺血性心脏病组p<0.0005）。冠状动脉外膜、心肌微血管和心内膜内皮中的微血管内皮细胞仅表达内皮素B受体。本研究中揭示的受体差异提供了支持性证据，表明内皮素-1与以下方面相关：（1）血管平滑肌和内皮细胞增殖，包括内膜增生区域和新生血管形成区域；（2）内皮素-1诱导的人类冠状动脉远端部分反应性增加；（3）内皮素-1介导的心肌微血管收缩。这些结果为该肽在健康和患病人类冠状动脉血管中的不同潜在作用提供了新的见解。
