Plasma matrix metalloproteinase-9 as a marker of blood stasis in varicose veins.
BACKGROUND
Possible intermediate circulating markers linking blood stasis to vein remodeling were explored in patients with varicose veins in the lower limbs.


RESULTS
Blood was sampled at rest (supine position) and after a stasis of 30 minutes both in the varicose vein (limbs hanging down) and in the brachial vein (arm hanging down) as a paired control. Several endothelial and leukocyte markers were measured in plasma with the use of ELISA kits. Angiotensin-converting enzyme activity was determined by use of a specific substrate. Matrix metalloproteinases (MMPs) 9 and 2 were evaluated with the use of gelatin zymography. No markers were significantly modified after 30 minutes of blood stasis in the brachial vein. After 30 minutes of blood stasis in the varicose vein, oxygen partial pressure decreased (P<0.01). Although thrombomodulin, von Willebrand factor, vascular endothelial growth factor, and MMP-2 were not modified in these conditions, the proteins released by proteolysis from the endothelial membrane intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and angiotensin-converting enzyme were increased (P<0.01). After blood stasis in varicose veins, the leukocyte markers lactoferrin, myeloperoxidase, and interleukin-8 were not modified, whereas L-selectin shed from leukocytes increased (P<0.05), and a major increase in pro-MMP-9, which is released from tertiary granules during polymorphonuclear activation, was observed (P=0.0001).


CONCLUSIONS
The marked increase in plasma pro-MMP-9 activity provides evidence of polymorphonuclear activation and granule release in the varicose vein in response to postural blood stasis. Similarly, detection in the plasma of membrane proteins shed from the endothelium or leukocytes provides evidence of pericellular proteolysis.
Jacob
Marie-Paule
MP
INSERM U460, CHU Xavier Bichat, Paris, France. jacob@bichat.inserm.fr
Cazaubon
Michèle
M
Scemama
Anthony
A
Prié
Dominique
D
Blanchet
Françoise
F
Guillin
Marie-Claude
MC
Michel
Jean-Baptiste
JB
D001132:Arm / Q000098:blood supply / Q000502:physiology; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D001784:Blood Gas Analysis; D015815:Cell Adhesion Molecules / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007866:Leg / Q000098:blood supply / Q000503:physiopathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology; D010100:Oxygen / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011187:Posture; D011237:Predictive Value of Tests; D012039:Regional Blood Flow; D014463:Ultrasonography; D014648:Varicose Veins / Q000175:diagnosis* / Q000503:physiopathology*; D014680:Veins / Q000000981:diagnostic imaging / Q000502:physiology
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D007703:Peptidyl-Dipeptidase A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D010100:Oxygen