title: Endothelin receptors in the aetiology and pathophysiology of varicose veins.
abstract: 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.
authors.affiliation: Department of Surgery, Royal Free and University College Medical School, Pond Street, London, NW3 2QG, UK.
authors.forename: O
authors.initials: O
authors.lastname: Agu
authors.forename: G
authors.initials: G
authors.lastname: Hamilton
authors.forename: D M
authors.initials: DM
authors.lastname: Baker
authors.forename: M R
authors.initials: MR
authors.lastname: Dashwood
mesh_terms: 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*
chemical_list: D019332:Endothelin-1; D017466:Receptors, Endothelin