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.