Evaluation of transforming growth factor-beta signaling pathway in the wall of normal and varicose veins.
OBJECTIVE
Extracellular matrix remodeling in the vein wall is involved in varicose vein pathogenesis, with transforming growth factor beta(1) (TGF-beta(1)) playing a potential role. The aim of the study was to assess the TGF-beta signaling pathway including its receptor (TGF-beta RII) and phosphorylated receptor-regulated Smads (p-Smad2/3) in varicose veins.


METHODS
Varicose veins from patients undergoing varicose vein surgery were the studied material, whereas normal greater saphenous veins from patients undergoing infrainguinal arterial bypass surgery were the control material. Expression of TGF-beta RII mRNA was assessed with RT-PCR, whereas expression of TGF-beta RII and p-Smad2/3 proteins was assessed with Western blot.


RESULTS
A significantly increased TGF-beta RII mRNA level was found in varicose veins (287 +/- 24%), when compared with normal veins (100 +/- 26%). The receptor protein expression reflected a changed mRNA level with significantly increased TGF-beta RII protein in varicose veins (290 +/- 21%), when compared with controls (100 +/- 16%). Enhanced TGF-beta RII expression was accompanied by increased p-Smad2/3 protein expression in varicose veins (257 +/- 19%) in comparison with normal veins (100 +/- 9%).


CONCLUSIONS
Increased TGF-beta RII expression and activation in the wall of varicose veins may be involved in extracellular matrix remodeling related to TGF-beta(1) and supports its role in the disease pathogenesis.
Kowalewski
Radoslaw
R
Department of Vascular Surgery and Transplantology, Medical University of Bialystok, PL-15-276 Bialystok, Poland. korado@2com.pl
Malkowski
Andrzej
A
Sobolewski
Krzysztof
K
Gacko
Marek
M
D000328:Adult; D015153:Blotting, Western; D002352:Carrier Proteins; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D012501:Saphenous Vein / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014648:Varicose Veins / Q000378:metabolism* / Q000473:pathology
D002352:Carrier Proteins; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II