Plasma apolipoprotein(a) co-deposits with fibrin in inflammatory arthritic joints.
Extravascular coagulation and diminished fibrinolysis are processes that contribute to the pathology of both inflammatory arthritis and atherosclerosis. We hypothesized that, given its homology with plasminogen, apolipoprotein (apo) (a), the distinctive glycoprotein of the atherogenic lipoprotein (Lp) (a), may be equally implicated in inflammatory arthritis. We detected the presence of apo(a) as part of Lp(a) in human arthritic synovial fluid. The 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, was detected in inflammatory arthritic synovial tissues. These data indicated that synovial fluid apo(a) originates from circulating Lp(a) and that diffusion 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-localization of apo(a) with fibrin in synovial tissue suggests that, in humans, apo(a) may modulate locally the fibrinolytic activity and may thus contribute to the persistence of intra-articular fibrin in inflammatory arthritis.
Busso
N
N
Division of Rheumatology, Centre Hospitalier Universitaire Vaudois University Hospital, Lausanne, Switzerland.
Dudler
J
J
Salvi
R
R
Péclat
V
V
Lenain
V
V
Marcovina
S
S
Darioli
R
R
Nicod
P
P
So
A K
AK
Mooser
V
V
D000818:Animals; D000941:Antigens / Q000276:immunology; D001054:Apolipoproteins A / Q000097:blood / Q000378:metabolism*; D001168:Arthritis / Q000276:immunology / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D007596:Joints / Q000378:metabolism*; D017270:Lipoprotein(a) / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010003:Osteoarthritis / Q000378:metabolism; D010316:Particle Size; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism
D000941:Antigens; D001054:Apolipoproteins A; D017270:Lipoprotein(a); D005337:Fibrin