Aberrant vascularity and von Willebrand factor distribution in inflamed synovial membrane.
OBJECTIVE
Von Willebrand factor (vWF) is an adhesive glycoprotein produced and secreted constitutively by endothelial cells. vWF is released upon endothelial stimulation and/or vascular injury, and mediates adhesion and aggregation of platelets. Our aim was to quantify synovial vasculature and to evaluate vWF distribution in situ in synovial membranes in various arthritides.


METHODS
Immunohistochemical staining of vWF in synovial membranes from patients with rheumatoid arthritis (RA) (N = 9), psoriatic (PsA) (N = 3), and reactive (ReA) (N = 4) arthritis, and from 6 noninflammatory controls: osteoarthritis (N = 1), chondromatosis (N = 1), meniscus lesion (N = 4). Morphometric assessments were performed with an image analyzer.


RESULTS
In RA, mean number of blood vessels/mm2 in the thickened synovium was relatively low (131 +/- 57 vs control 257 +/- 115, p = 0.0137, ReA 346 +/- 83, p = 0.0002, PsA 434 +/- 157, p = 0.0127). In particular, the superficial layer, corresponding to the thickness of normal synovial membrane (i.e., 56 +/- 5 microns), was sparsely vascularized (70 +/- 37 in the superficial vs 219 +/- 104 in the deeper layer, p = 0.0047). Synovial thickening was not seen in ReA and PsA. In accordance with its constitutive metabolism, vWF was found in the endothelial cells, inside the blood vessels, and in the subendothelium. In addition, RA was characterized by weak endothelial immunoreactivity and perivascular vWF. In ReA, perivascular vWF staining was visible in areas of inflammatory cell infiltrates.


CONCLUSIONS
Morphometric findings indicate decreased vascularization of the superficial synovial membrane in RA. Second, vWF may play a role in the inflammatory/reparative responses in synovium in RA and ReA, which were characterized by vascular stimulation/injury and abnormal vWF distribution.
Ceponis
A
A
ORTON Research Institute, Orthopaedic Hospital, Invalid Foundation, Helsinki, Finland.
Konttinen
Y T
YT
MacKevicius
Z
Z
Solovieva
S A
SA
Hukkanen
M
M
Tamulaitiene
M
M
Matulis
A
A
Santavirta
S
S
D000293:Adolescent; D000328:Adult; D001168:Arthritis / Q000209:etiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007719:Knee Joint / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D000091402:Prohibitins; D013583:Synovial Membrane / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D013585:Synovitis / Q000209:etiology* / Q000473:pathology; D014841:von Willebrand Factor / Q000096:biosynthesis*
C000717331:PHB2 protein, human; D000091402:Prohibitins; D014841:von Willebrand Factor