A role for angiogenesis in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic debilitating disease characterized by distinct autoimmune, inflammatory and fibrovascular components which lead to synovial proliferation and joint destruction. However, existing treatments specifically target only autoimmune and inflammatory components despite the fact that neovascularization of the inflamed synovium is a hallmark of rheumatoid arthritis. Angiogenesis may contribute to synovial growth, leukocyte recruitment and tissue remodeling, thus potentiating disease progression. Although no therapies currently target angiogenesis, several existing therapies have anti-angiogenic activity. Recent advances in anti-angiogenic strategies in oncology, including the identification of integrin avß3 as a crucial effector of angiogenesis, suggest a means to assess the role of angiogenesis in rheumatoid arthritis. Synovial endothelial cells have been shown to express integrin avß3, suggesting that these cells may be targeted for angiogenesis inhibition. Prior studies in rat arthritis models have shown benefit after the addition of broad spectrum integrin antagonists. However, formal assessment of integrin-targeted anti-angiogenic activity is now underway. These controlled studies will be important in assessing the efficacy of therapies which target angiogenesis in RA.

Expression of endoglin (CD105) in cervical cancer

“…Tumour-associated macrophages are known to contain many proangiogenic factors, such as VEGF (Leek et al, 2000), TNF-a (Pusztai et al, 1994), CXCL-8 (Fujimoto et al, 2000), bFGF (Stupack et al, 1999) and proteases such as MMP-2 and MMP-9 (Pollard, 2004). These MMPs are able to free pro-angiogenic cytokines, such as TGF-b and VEGF-A, from the matrix.…”

Inflammation, Immune Reactivity, and Angiogenesis in a Severe Combined Immunodeficiency Model of Rheumatoid Arthritis

“…Angiogenesis, or the development of a network of new blood vessels is one of the earliest histopathological alterations in the synovium and seems to be required for synoviocyte hyperplasia. 1,4,5 Whereas, all human endothelium express high levels of CD31 (PECAM-1), recent studies suggest that only vessels undergoing angiogenesis express the integrin ␣v␤3 or CD51/CD61. 6,7 Endothelial cells in inflamed tissue also express the activation marker, VAP-1.…”

NK95806, a newly synthesized microtubule-disrupting agent that suppresses collagen-induced arthritis in mice

“…Several kinds of cells and soluble factors are involved in the development of the disease but the involvement of immunological processes such as antigen presentation or T cell responses other than in the initial step is controversial. From a therapeutic point of view, the inhibition of invasion, angiogensis and fibrosis in the subsynovial layer and following pannus formation are attractive [12]. MTX is now classified as a first choice anti-RA drug because of its improved efficacy [13].…”