Angiogenesis in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with unknown etiology, characterized by perpetuated inflammation, pannus formation, and joint destruction. The formation of new blood vessels-termed ”angiogenesis”-is now recognized as a key event in the perpetuation of RA synovitis. There is plenty of evidence supporting this hypothesis, including the expression of pro-angiogenic factors in synovial tissue and the inhibition of angiogenesis ameliorating the disease severity in animal models of arthritis. Recent studies have shown that neovasculature in RA synovium not only arises through the budding of pre-existing vessels (angiogenesis), but also results from the recruitment of blood vessels in a bone marrow-origin progenitor population (vasculogenesis). Although many pro-angiogenic factors have been identified, vascular endothelial growth factor (VEGF) has a central role in the angiogenic process. VEGF is also involved in endothelial progenitor cells mobilization. The US Food and Drug Administration (FDA) approved the anti-VEGF antibody, bevacizumab, the first angiogenesis inhibitor, for metastatic colorectal cancer in 2004. Numerous clinical trials are testing this with various angiogenic diseases. There are expectations that oncologic therapies that block VEGF activity will also be applicable to RA in the future, to reduce synovial angiogenesis and pannus proliferation. More recently, interleukin-13 gene therapy in a rat model of RA, and some other novel agents in animal studies, such as PPI-2458, endostatin, and FK 228, have all showed anti-angiogenic effects. In addition, some natural compounds, such as sinomenine and wogonin, can inhibit angiogenesis. The present review will update our understanding of the role of angiogenesis in RA, and the prospects for anti-angiogenic therapy in RA.