Association of primary varicose veins with dysregulated vein wall apoptosis.
BACKGROUND
Disordered programmed cell death may play a role in the development of superficial venous incompetence. We have determined the number of cells in apoptosis, and the mediators regulating the intrinsic and extrinsic pathways in specimens of varicose vein.


METHODS
Venous segments were obtained from 46 patients undergoing surgical treatment for primary varicose veins. Controls samples were obtained from 20 patients undergoing distal arterial bypass grafting surgery. Segments of the distal and proximal saphenous trunk as well as tributaries were studied. Cell apoptoses and mediators of the mitochondrial and trans membrane pathway were evaluated with peroxidase in situ apoptosis detection, Bax and Fas detection, caspase-9 and 8 detection in the medial layer.


RESULTS
Disorganised histological architecture was observed in varicose veins. Primary varicose veins also contained fewer peroxidase in situ-positive cells than control veins (2.6% S.D. 0.2% versus 12% S.D. 0.93%, P=.0001, Mann-Whitney u test), fewer Bax positive cells (2.1.% S.D. 0.3% versus 13% S.D. 0.9%, P=.0001) and fewer Caspase 9 positive cells (3.2% S.D. 1% versus 12% S.D. 1.3%, P=.0001). Similar findings were observed in saphenous trunk, main tributaries and accessory veins. In patients with recurrent varicose veins in whom the saphenous trunk had been preserved showed similar findings to primary varicose veins. Residual varicose veins contained fewer peroxidase in situ-positive cells than healthy veins (3.2% S.D. 0.6% versus 11% S.D. 2%, P=.0001), fewer Bax positive cells (2.2% S.D. 0.3% versus 12% S.D. 0.7%, P=.0001) and fewer Caspase 9 positive cells (2.6% S.D. 0.6% versus 12% S.D. 1%, P=.0001). Immunohistochemical detection for Fas and caspase 8 remained equal was the same in the varicose vein and control groups.


CONCLUSIONS
Apoptosis is down regulated in the medial layer of varicose veins. This dysregulation is attributable to a disorder of the intrinsic pathway and involves the great saphenous vein trunk, major tributaries and accessory veins. This process may be among the causes of primary varicose veins.
Ducasse
E
E
Unit of Vascular Surgery, Hospital Tripode-Pellegrin, Université de Bordeaux 2, CHU de Bordeaux, Bordeaux, France. eric.ducasse@online.fr
Giannakakis
K
K
Speziale
F
F
Midy
D
D
Sbarigia
E
E
Baste
J C
JC
Faraggiana
T
T
D017209:Apoptosis; D053181:Caspase 8 / Q000032:analysis; D053453:Caspase 9 / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D012501:Saphenous Vein / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D017540:Tunica Media / Q000473:pathology* / Q000601:surgery; D014648:Varicose Veins / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D051028:bcl-2-Associated X Protein / Q000032:analysis; D019014:fas Receptor / Q000032:analysis
C494826:BAX protein, human; C491901:FAS protein, human; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; C505530:CASP8 protein, human; D053181:Caspase 8; D053453:Caspase 9