Department of Clinical Biochemistry, Royal Free and University College Medical School, Pond Street, London, NW3 2QG, UK,
J Cell Commun Signal. 2011 Mar;5(1):45-9. doi: 10.1007/s12079-010-0109-8. Epub 2010 Nov 27.
Critical limb ischaemia (CLI), due to atherosclerotic arterial occlusion, affects over 20,000 people per year in the United Kingdom with many facing lower limb amputation and early death. A role for endothelin-1 (ET-1) in atherosclerosis is well-established and increased circulating and tissue levels of this peptide have been detected in patients with CLI. ET-1 and its receptors were identified in atherosclerotic popliteal arteries obtained from CLI patients undergoing lower limb amputation. In addition, plasma ET-1 levels were compared with those of non-ischaemic controls. ET-1 was associated with regions of atherosclerotic plaque, particularly in regions with high macrophage content. This peptide was also associated with endothelial cells lining the main vessel lumen as well as adventitial microvessels. ET(A) and ET(B) receptors were located within regions of plaque, adventitial microvessels and perivascular nerves. There was a statistically significant increase (P < 0.001) in plasma ET-1 in CLI patients when compared with controls. These results reveal sources of ET-1 in atherosclerotic popliteal arteries that potentially contribute to increased circulating levels of this peptide. Identification of variable receptor distributions in ischaemic tissue suggests a therapeutic potential of selective receptor targeting in patients with CLI.
严重肢体缺血（CLI）是由动脉粥样硬化性闭塞引起的，每年在英国影响超过 20000 人，许多人面临下肢截肢和早逝。内皮素-1（ET-1）在动脉粥样硬化中的作用已得到充分证实，在 CLI 患者中检测到循环和组织中这种肽的水平升高。在接受下肢截肢的 CLI 患者的动脉粥样硬化性腘动脉中鉴定出 ET-1 及其受体。此外，还比较了血浆 ET-1 水平与非缺血对照者的水平。ET-1 与动脉粥样硬化斑块的区域相关，特别是在巨噬细胞含量高的区域。这种肽还与主要血管腔的内皮细胞以及外膜微血管相关。ET（A）和 ET（B）受体位于斑块区域、外膜微血管和血管周围神经内。与对照组相比，CLI 患者的血浆 ET-1 显着增加（P<0.001）。这些结果揭示了动脉粥样硬化性腘动脉中 ET-1 的来源，这可能导致这种肽的循环水平升高。在缺血组织中鉴定出可变的受体分布表明选择性受体靶向在 CLI 患者中具有治疗潜力。
