Hasdai D, Holmes D R, Garratt K N, Edwards W D, Lerman A
Division of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minn., USA.
Circulation. 1997 Jan 21;95(2):357-62. doi: 10.1161/01.cir.95.2.357.
Endothelin-1 (ET-1) is an endothelium-derived vasoactive peptide with mitogenic properties. In vitro, vascular release of ET-1 is increased in response to mechanical stress. The goal of the present study was to examine whether ET-1 is released from human atherosclerotic coronary arteries in vivo in response to mechanical pressure and stretch and to characterize immunoreactivity for ET-1 and its precursor, big ET-1, within the atheromatous plaque.
Circulating ET-1 levels were measured in 20 patients before and after coronary angioplasty for stable angina at three sampling sites: the femoral artery and the coronary artery segments proximal and distal to the lesion dilated. In addition, atheromatous tissue obtained from 20 patients undergoing directional coronary atherectomy for stable angina were analyzed for immunoreactivity for ET-1 and big ET-1. In patients undergoing angioplasty, ET-1 levels in the distal coronary artery increased after balloon dilatation (8.4 +/- 0.9 to 16.4 +/- 2 pg/mL, P < .05); proximal coronary artery and systemic ET-1 levels were unchanged. The degree of mechanical stress applied (product of duration and pressure of balloon inflation) correlated with the change in distal coronary artery ET-1 levels (r = .71, P < .01). Immunoreactivity for big ET-1 and ET-1 was ubiquitous in the extracellular space and the intracellular compartment (macrophages, myointimal cells, myofibroblasts, and endothelial cells) of human coronary atheromatous tissue.
Big ET-1 and ET-1 immunoreactivity is ubiquitous within the intracellular and extracellular compartments of coronary atherosclerotic tissue. ET-1 is released from these sites in response to mechanical stress. These findings support a role for endothelins in the evolution and progression of coronary atherosclerosis in humans.
内皮素 -1（ET-1）是一种具有促有丝分裂特性的内皮源性血管活性肽。在体外，ET-1的血管释放会因机械应力而增加。本研究的目的是检测ET-1在体内是否会因机械压力和拉伸而从人类动脉粥样硬化冠状动脉中释放出来，并对动脉粥样斑块内ET-1及其前体大ET-1的免疫反应性进行表征。
在20例因稳定型心绞痛接受冠状动脉血管成形术的患者中，于三个采样部位（股动脉以及病变扩张部位近端和远端的冠状动脉节段）测量冠状动脉血管成形术前和术后循环中ET-1的水平。此外，对20例因稳定型心绞痛接受冠状动脉定向旋切术的患者所获取的动脉粥样硬化组织进行ET-1和大ET-1免疫反应性分析。在接受血管成形术的患者中，球囊扩张后远端冠状动脉中的ET-1水平升高（从8.4±0.9升高至16.4±2 pg/mL，P<.05）；近端冠状动脉和全身ET-1水平未发生变化。施加的机械应力程度（球囊膨胀持续时间与压力的乘积）与远端冠状动脉ET-1水平的变化相关（r =.71，P<.01）。大ET-1和ET-1的免疫反应性在人类冠状动脉粥样硬化组织的细胞外空间和细胞内区室（巨噬细胞、肌内膜细胞、肌成纤维细胞和内皮细胞）中普遍存在。
大ET-1和ET-1的免疫反应性在冠状动脉粥样硬化组织的细胞内和细胞外区室中普遍存在。ET-1会因机械应力而从这些部位释放出来。这些发现支持内皮素在人类冠状动脉粥样硬化的发生和发展中起作用。
