Sulodexide may alleviate neointimal hyperplasia by inhibiting angiopoietin-2 in an arteriovenous fistula model

Abstract

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.