Plasma apolipoprotein(a) co-deposits with fibrin in inflammatory arthriticjoints

Extravascular coagulation and diminished fibrinolysis are processes that co ntribute to the pathology of both inflammatory arthritis and atherosclerosi s. We hypothesized that, given its homology with plasminogen, apolipoprotei n (apo) (a), the distinctive glycoprotein of the atherogenic lipoprotein (L p) (a), may be equally implicated in inflammatory arthritis. We detected th e presence of apo(a) as part of Lp(a) in human arthritic synovial fluid. Th e abundance of apo(a) in synovial fluid rose in proportion to plasma apo(a) levels and was higher in inflammatory arthritides than in osteoarthritis. in addition, apo(a) immunoreactive material, but not apo(a) transcripts, wa s detected in inflammatory arthritic synovial tissues. These data indicated that synovial fluid apo(a) originates from circulating Lp(a) and that diff usion of Lp(a) through synovial tissue is facilitated in inflammatory types of arthritis. In synovial. tissues, apo(a) co-localized with fibrin. These observations could be reproduced in a model of antigen-induced arthritis, using transgenic mice expressing human Lp(a). Although in this mouse model the presence of apo(a) did not change the severity of arthritis, the co-loc alization of apo(a) with fibrin in synovial tissue suggests that, in humans , apo(a) may modulate locally the fibrinolytic activity and may thus contri bute to the persistence of intra-articular fibrin in inflammatory arthritis .