The kinin B(1) receptor and inflammation: new therapeutic target for cardiovascular disease.
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.
Duchene
Johan
J
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. j.duchene@qmul.ac.uk
Ahluwalia
Amrita
A
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000276:immunology; D001920:Bradykinin / Q000378:metabolism; D065169:Bradykinin B1 Receptor Antagonists; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D016503:Drug Delivery Systems; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007609:Kallidin / Q000378:metabolism; D007674:Kidney Diseases / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D065169:Bradykinin B1 Receptor Antagonists; D018836:Inflammation Mediators; D043783:Receptor, Bradykinin B1; D007609:Kallidin; D001920:Bradykinin