New antiangiogenic strategies for the treatment of proliferative synovitis

摘要

Angiogenesis inhibition,which has been extensively studied for the treatment of various malignancies,is beginning to emerge as a new potential therapy for proliferative synovitis,particularly rheumatoid arthritis(RA).The rheumatoid pannus,the site of inflammation and joint destruction in the rheumatoid synovium,relies on the development of new vasculature to sustain its growth.A host of mediators have been shown to induce angiogenesis at the site of the inflamed synovium;these include vascular endothelial growth factor,fibroblast growth factor,integrin alpha_Vbeta_3,angiopoietin,prosta-glandin E_1 and prostaglandin E_2,and matrix metalloproteinases.In addition,hypoxia at the site of synovial inflammation contributes to angiogenesis stimulation.Several naturally-occurring inhibitors exist,such angiostatin and endostatin.There are a number of drugs undergoing study in the treatment of proliferative synovitis,which capitalise on the correlation between angiogenesis inhibition and the reduction of signs and symptoms of RA.Paclitaxel and an anti-integrin alpha_vbeta_3 antibody,LM-609,are currently in clinical trials.Other drugs that may inhibit angiogenesis in RA include TNP-470(formerly called AGM-1470),PPI-2458,PTK-787,bevacizumab and thalidomide.Many of these drugs have shown promise for the treatment of oncologic disorders,and are now being evaluated for the treatment of proliferative synovitis.