Skin damage in the presence of chronic venous disease is partially mediated through leukocytes. The endothelium is activated and exhibits proliferation in the skin. Up-regulation of vascular endothelial growth factor (VEGF) expression in the skin of patients with chronic venous disease has been demonstrated with immunohistologic techniques. Abnormal VEGF expression can have local deleterious effects. The aim of this study was to determine whether patients with chronic venous disease have elevated plasma levels of VEGF. We conducted a prospective study with 30 patients with varicose veins of clinical, etiologic, anatomic, and pathologic class C3 (normal skin, n = 15) and C4 (trophic skin changes, n = 15) and 25 control subjects with no clinical evidence of venous or arterial disease of the lower limb. Blood samples were collected from a foot vein of each subject before and after a period of experimental venous hypertension produced by means of standing. Assay of VEGF protein was performed with a sandwich enzyme-linked immunosorbent assay. Plasma VEGF level was elevated in both groups of patients with venous disease compared with the control group. The median VEGF levels among patients were 81 pg/mL (interquartile range [IQR] 56 to 122) supine and 98 pg/mL (IQR 63 to 153) after standing for 30 minutes. Median VEGF levels among control subjects were 52 pg/mL (IQR 35 to 71) lying supine and 60 pg/mL (IQR 39 to 105) after standing for 30 minutes. Experimental venous hypertension caused a small rise in VEGF levels among the patients but not the control subjects. Further studies are required to determine whether increased VEGF expression contributes to tissue injury in chronic venous disease.

Micronised purified flavonoidic fraction treatment for 60 days seems to decrease the levels of some plasma markers of endothelial activation. This could ameliorate the dermatological effects of (CVD). This could also explain some of the pharmacological actions of these compounds. Our study demonstrates the feasibility of using soluble endothelial adhesion molecules as markers for treatment.

Micronized purified flavonoid fraction treatment for 60 days seems to decrease the surface expression of CD62L by neutrophils and by monocytes. The clinical significance of this finding needs to be explored further. It is feasible to use changes in the levels of these molecules as a marker for response to therapy in chronic venous disease.

plasma VEGF levels were much higher in patients who have skin changes of CVD. Plasma VEGF protein decreases in patients with CVD-induced dermatologic changes following treatment with purified micronised flavonoid fraction.

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