Primary varicose veins: altered transcription of VEGF and its receptors (KDR, flt-1, soluble flt-1) with sapheno-femoral junction incompetence.
OBJECTIVE
Loss of regulation of vascular endothelial growth factor (VEGF) production and action disturbs vascular homeostasis leading to pathology. Primary varicose veins (VVs) demonstrate aberrant production/release of VEGF. Our aim was to examine transcription of genes for VEGF (VEGF(121)/VEGF(165)) and its receptors (KDR, flt-1, s.flt-1) in VVs, in relation to underlying venous incompetence.


METHODS
Samples of varicose (n=83, 18 patients) or normal (n=14, five subjects) great saphenous vein were divided into segments, determined by anatomical position from the sapheno-femoral junction (SFJ). SFJ and segmental incompetence were determined from duplex scans. Gene transcripts were amplified by RT-PCR, analysed by scanning densitometry, and the levels of transcription determined by ratio to control gene GADPH-3 (GAP-3).


RESULTS
VEGF(121)/(165), KDR and flt-1 transcription was elevated in VVs overall (p<0.001), and in VVs with an incompetent SFJ (p<0.001), but not when the SFJ was functional; s.flt-1 was unaltered. Notably, gene transcription was unaffected by segmental position, or incompetence. Position below the SFJ correlated with increased transcription of s.flt-1 when the SFJ was incompetent (p<0.04), and s.flt-1 and VEGF(121) when the segment was incompetent (p<0.03).


CONCLUSIONS
SFJ incompetence is associated with altered transcription of VEGF and its receptors reflecting an aetiological mechanism or later stage of disease development. Altered VEGF(121) and s.flt-1 transcription may be an early event in varicogenesis.
Hollingsworth
S J
SJ
The Academic Vascular Unit, Department of Surgery, The Royal Free and University College Medical School London, The Middlesex Hospital, Mortimer Street, London, UK.
Powell
G l
Gl
Barker
S G E
SG
Cooper
D G
DG
D000328:Adult; D000368:Aged; D005260:Female; D005268:Femoral Vein / Q000503:physiopathology; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics; D011956:Receptors, Cell Surface; D012501:Saphenous Vein / Q000503:physiopathology; D012995:Solubility; D014158:Transcription, Genetic; D014648:Varicose Veins / Q000235:genetics* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2