Duchene Johan, Ahluwalia Amrita
The William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom.
Curr Opin Pharmacol. 2009 Apr;9(2):125-31. doi: 10.1016/j.coph.2008.11.011. Epub 2009 Jan 3.
The kinin B(1) receptor plays an important role in mediating the inflammatory effects of the kallikrein-kinin pathway. The recent development of orally available non-peptidic antagonists and genetically modified mice deficient in B(1) receptor expression have demonstrated that the receptor plays a pivotal role in the cellular, particularly neutrophil, recruitment associated with an acute inflammatory response. These tools have also enabled elucidation of the pathways involved in mediating this effect and have highlighted a major role for chemokines, particularly CXCL5 and CCL2. Neutrophil recruitment is involved in the pathogenesis of renal disease and has very recently been implicated in the early stages of atherosclerosis. In this review we discuss the most recent evidence linking the B(1) receptor with the pathogenesis of these two inflammatory cardiovascular diseases and highlight the therapeutic potential of the kinin B(1) receptor in these disease states.
激肽B(1)受体在介导激肽释放酶-激肽途径的炎症效应中起重要作用。口服可用的非肽类拮抗剂的最新进展以及缺乏B(1)受体表达的基因改造小鼠已证明,该受体在与急性炎症反应相关的细胞,特别是中性粒细胞募集中起关键作用。这些工具还使得阐明介导这种效应的途径成为可能,并突出了趋化因子,特别是CXCL5和CCL2的主要作用。中性粒细胞募集参与肾脏疾病的发病机制,并且最近已被证明与动脉粥样硬化的早期阶段有关。在本综述中,我们讨论了将B(1)受体与这两种炎症性心血管疾病的发病机制联系起来的最新证据,并强调了激肽B(1)受体在这些疾病状态下的治疗潜力。