angiogenin and Arthritis

Angiogenesis is a key process in the pathogenesis of inflammatory arthritis. Angiogenin is one of the most potent inducers of neovascularization in experimental models in vivo. To look for evidence that angiogenin is involved in inflammatory joint disease, we examined plasma and synovial fluid (SF) samples from rheumatology patients and synovial fibroblast cell culture supernatants. Angiogenin levels were determined by radioimmunoassay and ELISA. Plasma angiogenin concentrations ranged from 96 to 478 ng/ml, with no significant difference between patients and normal controls. In SF, angiogenin concentrations were significantly higher in patients with acute or chronic synovitis (rheumatoid arthritis (RA): median, 104 ng/ml; range 13-748, n = 14; crystal-induced arthritis (CIA): median, 149 ng/ml; range, 37-616, n = 14, and other chronic inflammatory arthritis: median, 42 ng/ml; range, 15-205; n = 9) than in the 18 patients with osteoarthritis (OA) (median, 20 ng/ml; range 8-116) (P < 0.0001, anova). Angiogenin levels in SF from RA patients in remission with secondary OA were similar to those achieved in primary OA, and decreased in parallel with the resolution of acute gout. Angiogenin protein was released by cultured synovial fibroblasts from OA and RA patients, and reached 1.18 ng/106 cells/day. These data suggest that angiogenin may mediate local inflammation in arthritis via effects on angiogenesis and leucocyte regulation.

Topics: Analysis of Variance; Arthritis; Arthritis, Infectious; Arthritis, Psoriatic; Arthritis, Rheumatoid; Case-Control Studies; Cells, Cultured; Culture Media, Conditioned; Fibroblasts; Humans; Leukocytes, Mononuclear; Osteoarthritis; Ribonuclease, Pancreatic; Statistics, Nonparametric; Synovial Fluid

Angiogenesis is an integral component of the vasculoproliferative phase of rheumatoid arthritis (RA). We examined the distribution of two angiogenic factors, basic fibroblast growth factor (bFGF) and angiogenin (ANG) in arthritic diseases. We used an enzyme-linked immunosorbent assay and immunohistochemical analysis to determine the levels of bFGF and ANG in synovial fluid (SF) and their distribution in synovial tissue (ST), respectively. Most SF contained little or no detectable bFGF ( < 5 pg/ml). ANG in RA SF was 248.7 +/- 17.4 ng/ml, which did not differ significantly from levels found in osteoarthritis (OA; 305.9 +/- 23.1 ng/ml). Synovial lining cells, macrophages, endothelial cells, and vascular smooth muscle cells were immunopositive for bFGF and ANG; however, their expression was not up-regulated in RA ST compared to ST from OA and normal subjects. Though bFGF and ANG are present in the joints of patients with arthritic diseases, they are not up-regulated in RA. These results suggest that not all angiogenic mediators are up-regulated in RA compared to normal subjects and subjects with other arthritic diseases. It may be that some of these mediators, like ANG, play a role in the physiology of normal synovium.

Topics: Angiogenesis Inducing Agents; Arthritis; Arthritis, Rheumatoid; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Fibroblast Growth Factor 2; Fibroblasts; Humans; Immunohistochemistry; Osteoarthritis; Protein Biosynthesis; Proteins; Ribonuclease, Pancreatic; Synovial Fluid; Synovial Membrane; Up-Regulation