Exercise induced release of von Willebrand factor: evidence for hypoxic reperfusion microvascular injury in rheumatoid arthritis.
Experimental evidence suggests that rheumatoid synovitis may be perpetuated by the generation of reactive oxygen species during hypoxic reperfusion injury. The latter occurs because increased intra-articular pressure during exercise exceeds synovial capillary perfusion pressure, impairing blood flow. The object of this study was to establish a marker for and the mechanism of synovial hypoxic reperfusion injury. Von Willebrand factor (vWF) is only released from endothelial cells and platelets and is an in vivo and in vitro marker of endothelial injury. In vivo exercise induced changes in plasma vWF were therefore investigated in patients with rheumatoid arthritis (RA) compared with controls and in vitro vWF release by human umbilical vein endothelial cells subjected to hypoxia reperfusion. Pre-exercise plasma vWF levels were 1001 and 817 IU/l, increasing after exercise to 1658 and 845 IU/l in patients with RA and controls respectively. Von Willebrand factor release from human umbilical vein endothelial cells followed a biphasic pattern, occurring during both hypoxia and reperfusion. Hypoxia reperfusion induced vWF release by human umbilical vein endothelial cells in vitro suggests that exercise induced vWF release in patients with RA is best explained by synovial hypoxic reperfusion injury. This study supports evidence that generation of reactive oxygen species plays a principal part in synovial hypoxic reperfusion injury and suggests vWF as a useful marker of this phenomenon.
Farrell
A J
AJ
Inflammation Research Group, London Hospital Medical College, Whitechapel, United Kingdom.
Williams
R B
RB
Stevens
C R
CR
Lawrie
A S
AS
Cox
N L
NL
Blake
D R
DR
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D015427:Reperfusion Injury / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism*; D014471:Umbilical Veins / Q000378:metabolism / Q000648:ultrastructure; D014841:von Willebrand Factor / Q000096:biosynthesis*
D015415:Biomarkers; D014841:von Willebrand Factor