Changes of the serum properties and its effect on the endothelial cells restoration in patients with chronic disease treated with sulodexide.

ABSTRACT

OBJECTIVE: Inflammation and endothelial dysfunction are important venous changes in patients with chronic venous disease (CVD). The use of the venoactive drugs remains an important treatment modality for CVD patient, reducing severity of the CVD related symptoms and swelling but also reducting inflammation and protecting endothelial cells. In this research, the effects of the serum obtained from CVD patients before and after sulodexide treatment was evaluated for in vivo and in vitro inflammatory markers and endothelial cell function. MATERIAL AND METHODS: Inflammatory markers (IL-6, MMP-9, VCAM-1, vWF) from the incompetent great saphenous (GSV) veins and from the systemic venous circulation were studied in 10 CVD C2s patients before and after 2 months of sulodexide (2 x 500 LSU/day) therapy. Serum from pretreatment and following sulodexide treated patients was evaluated for in vitro cultured human umbilical vein endothelial cells (HUVEC) function. RESULTS: Serum collected from lower leg incompetent GSVs had significantly elevated levels of VCAM-1 (+ 29%, p<0.001) than serum from the systemic circulation. Endothelial cells exposed to the serum from the incompetent lower leg veins of the untreated CVD patients demonstrated higher stimulated synthesis of MMP-9 (+17%, p<0.01), as well as increased markers of senescence (prolongation of PDT, ß-galactosidase activity, expression of p21 and p53 genes). CVD serum induced senescent endothelial cells had a higher expression of genes regulating IL-6, MMP-9, VCAM-1 and vWF synthesis. The overall proinflammatory effect on endothelial cells by serum collected from incompetent GSV was stronger as compared to serum from the systemic circulation. Serum collected from the veins after sulodexide treatment caused lower levels of endothelial cell inflammatory markers as well as respective gene expression than serum obtained at the beginning of the study (before sulodexide treatment). Sulodexide application also reduced the inflammatory secretory activity of the senescent endothelial cells. Sulodexide treatment resulted in the decrease of the majority of the studied inflammatory parameters in both lower limb incompetent vein and systemic blood. CONCLUSIONS: In CVD patients there are significant differences between circulating inflammatory markers analyzed from the lower leg incompetent GSV segments compared to the systemic circulation, indicating a higher inflammatory condition in CVD. Treatment with sulodexide reduces the proinflammatory and endothelial cell activation proprieties of the serum from CVD patients.