Endothelin receptors in the aetiology and pathophysiology of varicose veins.
BACKGROUND
varicose veins are tortuous and poorly contractile. Their aetiology remains unclear. Neovascularisation has been suggested as a possible explanation. Endothelins are mitogenic, promoting proliferation and migration of endothelial cells via endothelin-B receptors. We hypothesise that endothelial cells and endothelin receptor density and distribution may play a role in the development of varicosis.


METHODS
saphenous vein segments from nine patients with varicose veins were compared to six controls. Slide-mounted sections were incubated in radioactive labelled endothelin-1 and receptor subtype-selective ligands and binding sites assessed using autoradiography. Endothelin-1 and endothelial cells were identified by immunohistochemistry and CD31-positive staining cells counted.


RESULTS
radioactive labelled endothelin-1 and endothelin-B receptor binding was reduced in varicose compared to control veins (p=0.04). Endothelin-A receptor binding was diffuse, with no difference in density in both groups (p=0.58). Endothelin-B receptor binding was diffuse with superimposed clusters. Although the density of medial endothelin-B receptor binding was reduced in the varicose group, more clusters were identified in this group compared to controls (p=0.005). CD-31 staining identified these clusters as endothelial cells.


CONCLUSIONS
the reduced endothelin-1 binding and endothelin-B receptor density may be partially responsible for the reduced vasocontractility in varicose veins. We speculate that the increase in endothelin-B receptor binding CD31-positive endothelial cells in varicose veins may potentially stimulate mitogenesis and migration, leading to new vessel formation.
Agu
O
O
Department of Surgery, Royal Free and University College Medical School, Pond Street, London, NW3 2QG, UK.
Hamilton
G
G
Baker
D M
DM
Dashwood
M R
MR
D001667:Binding, Competitive / Q000502:physiology; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology; D017466:Receptors, Endothelin / Q000378:metabolism*; D013194:Staining and Labeling; D014648:Varicose Veins / Q000209:etiology* / Q000378:metabolism*
D019332:Endothelin-1; D017466:Receptors, Endothelin