Pathological Importance of the Endothelin-1/ET(B) Receptor System on Vascular Diseases.
Pathological Importance of the Endothelin-1/ET(B) Receptor System on Vascular Diseases.
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DOI：
10.1155/2012/731970
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发表时间：
2012
影响因子：
2.1
通讯作者：
Matsumura Y
中科院分区：
文献类型：
--
作者：
Kitada K;Ohkita M;Matsumura Y
内皮素（ET）-1/ET受体系统的激活参与血管疾病如动脉粥样硬化、血管肥大和再狭窄的发展。ET受体拮抗剂是否有望成为治疗血管疾病的新工具仍有许多问题有待解决。尚未解决的关键点之一是ET受体亚型对每种血管疾病的功能作用，特别是ETB受体的病理生理作用。我们最近发现，选择性抑制ETB受体系统在血管损伤后新生内膜形成的发展中显示出有害作用。非选择性ETA/ETB受体拮抗剂与选择性ETA受体拮抗剂的疗效无明显差异。这些发现表明，尽管选择性ETB受体拮抗剂抑制血管重塑，但ETA受体系统的拮抗作用对于抑制血管重塑是必不可少的，而与ETB受体介导的作用的存在无关。此外，我们发现ET受体系统有助于血管疾病严重程度的性别差异，从而表明ET受体拮抗剂对血管疾病的疗效可能在性别之间存在差异。本文综述了ET-1/ETB受体系统在血管疾病中的作用及其性别差异。
Activation of the endothelin (ET)-1/ET receptor system is involved in the development of vascular diseases such as atherosclerosis, vascular hypertrophy, and restenosis. Some issues still remain unresolved including whether ET receptor antagonists are expected to become the new therapeutic tools for the treatment of vascular diseases. One of the unresolved critical points is the functional role of ET receptor subtypes on each vascular disease, in particular the pathophysiological roles of the ETB receptor. We recently demonstrated that selective inhibition of the ETB receptor system showed harmful effects in the development of neointimal formation after vascular injury. However, there was no apparent difference in the therapeutic effects between a nonselective ETA/ETB receptor antagonist and selective ETA receptor antagonist. These findings indicate that antagonism of the ETA receptor system is essential for suppressing vascular remodeling, irrespective of the presence of ETB-receptor-mediated actions, although the selective ETB receptor antagonist worsens vascular remodeling. In addition, we found that ET receptor systems contribute to sex differences in the severity of vascular disease, thereby suggesting that the efficacy of ET receptor antagonists for vascular diseases may differ between sexes. In this paper, we outline the roles of the ET-1/ETB receptor system on vascular diseases and its sex differences.