Sulodexide may alleviate neointimal hyperplasia by inhibiting angiopoietin‑2             in an arteriovenous fistula model.
The present study was undertaken to confirm whether sulodexide aleviates             neointimal hyperplasia by regulating angiopoietin/Tie in a rat femoral arteriovenous             fistula (AVF) model. Sprague Dawley rats were divided into four groups: sham,             model, treatment and treatment control. An arteriovenous shunt model was created             in the model and treatment groups. Sulodexide was subcutaneously administered             (10 mg/kg/day) 6 times per week for 8 weeks in the treatment and treatment control             groups. Histology and immunofluorescence were analyzed and the protein expression             of angiopoietin‑1, angiopoietin‑2, Tie‑2, p‑ERK and total‑ERK were tested by ELISA             and/or western blotting after 8 weeks. HE staining revealed that sulodexide was             able to partially alleviate intimal hyperplasia of remodeled veins in the AVF             model. Additionally, sulodexide was able to decrease angiopoietin‑2 and Tie‑2             expression while increasing angiopoietin‑1 expression in AVF tissue. Sulodexide             was also able to decrease ERK phosphorylation which was increased in the model.             Serum levels of soluble Tie-2 (sTie‑2) were also significantly decreased by sulodexide             compared with the model. Immunofluorescent analysis also confirmed that sulodexide             was able to decrease angiopoietin‑2 expression, possibly partially by inhibiting             endothelial cell proliferation. Sulodexide may alleviate venous intimal hyperplasia             by regulating the angiopoietin/Tie system, which may play a significant role in             assisting remodeled veins to cope with their new biomechanical environment, but             whether the angiopoietin/Tie system is beneficial or not requires further study.
Department of Nephrology, The First Affiliated Hospital, Sun Yat‑Sen University and Key Laboratory of Nephrology, Ministry of Health, Guangzhou 510080, PR China.
Yan
Y
Lei
Zhihua
Z
Zheng
Ying
Y
Wang
Yuyun
Y
Liu
Rongjun
R
Liu
Qingdong
Q
Xu
Xueqing
X
Yu
D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001164:Arteriovenous Fistula / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006965:Hyperplasia; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D042787:Receptor, TIE-2 / Q000097:blood; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D005343:Fibrinolytic Agents; D006025:Glycosaminoglycans; C007858:glucuronyl glucosamine glycan sulfate; D042787:Receptor, TIE-2