Primary Varicose Veins: Altered Transcription of VEGF and its Receptors (KDR, flt-1, Soluble flt-1) with Sapheno-femoral Junction Incompetence

Abstract

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 (VEGF121/VEGF165) and its receptors (KDR, flt-1, s.flt-1) in VVs, in relation to underlying venous incompetence.Materials and 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. VEGF121/165, 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 VEGF121 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 VEGF121 and s.flt-1 transcription may be an early event in varicogenesis.