Local and Systemic Endothelial Damage in Patients with CEAP C2 Chronic Venous Insufficiency: Role of Mesoglycan

Abstract

Chronic venous disease (CVD) involves complex pathophysiological mechanisms, particularly an imbalance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), contributing to venous remodeling and varicosities. Elevated MMP-2 and MMP-9 levels are commonly found in tissues affected by venous ulcers. Inflammation plays a central role in CVD, with higher levels of pro-inflammatory markers present in varicose veins compared to healthy ones. Syndecans, key components of the endothelial glycocalyx, are involved in inflammatory responses. Alterations in the glycocalyx structure are associated with vascular damage in both venous and arterial diseases. This study aimed to investigate inflammatory changes in CVD patients, focusing on glycocalyx damage and the therapeutic role of mesoglycan, a glycosaminoglycan-based drug. A prospective, monocentric study included 23 patients with C2 clinical-etiological-anatomical-pathological (CEAP) CVD. Serum samples were collected before and after mesoglycan treatment. Results showed significantly elevated levels of VCAM-1, MMP-2, MMP-9, SDC-1, IL-6, and IL-8 in blood from varicose veins versus the systemic circulation. Patients received 50 mg of mesoglycan orally every 12 h for 90 days. After treatment, a notable reduction in inflammatory markers was observed. These results support the hypothesis that mesoglycan may alleviate both local and systemic inflammation, providing insights into new therapeutic strategies for CVD management.

Keywords: chronic venous disease; glycocalyx; mesoglycan; syndecans; systemic inflammation.

Figure 1

Linear graph representing the effects of mesoglycan on VCAM-1 (ng/mL) levels from blood derived from varicose veins at baseline (T0) and after 90 days of treatment (T1). Each line of the multiple-line chart represents each of the 23 patients involved in this study. A statistically significant decrease in VCAM-1 values can be observed (660.6 [629.3–743.7] ng/mL at T1 vs. 763.5 [685.7–849.1] ng/mL at T0; p = 0.001). Statistical analysis was performed using a paired Wilcoxon test and p < 0.05 was considered statistically significant.

Figure 2

Linear graph representing the effects of mesoglycan on MMP-2 (ng/mL) levels from blood derived from varicose veins at baseline (T0) and after 90 days of treatment (T1). Each line of the multiple-line chart represents each of the 23 patients involved in this study. A statistically significant decrease in MMP-2 values can be observed (46.89 [40.92–66.78] ng/mL at T1 vs. 51.48 [46.94–88.39] ng/mL at T0; p = 0.0002). Statistical analysis was performed using a paired Wilcoxon test and p < 0.05 was considered statistically significant.

Figure 3

Linear graph representing the effects of mesoglycan on MMP-9 (ng/mL) levels from blood derived from varicose veins at baseline (T0) and after 90 days of treatment (T1). Each line of the multiple-line chart represents each of the 23 patients involved in this study. A statistically significant decrease in MMP-9 values can be observed (36.22 [25.03–64.24] ng/mL at T1 vs. 69.02 [39.89–96.74] ng/mL at T0; p = 0.003). Statistical analysis was performed using a paired Wilcoxon test and p < 0.05 was considered statistically significant.

Figure 4

Linear graph representing the effects of mesoglycan on TIMP-2 (ng/mL) levels from blood derived from varicose veins at baseline (T0) and after 90 days of treatment (T1). Each line of the multiple-line chart represents each of the 23 patients involved in this study. A statistically significant increase in TIMP-2 values can be observed (172.40 [118.97–211.29] ng/mL at T1 vs. 127.29 [98.14–175.98] ng/mL at T0; p = 0.003). Statistical analysis was performed using a paired Wilcoxon test and p < 0.05 was considered statistically significant.

Figure 5

Linear graph representing the effects of mesoglycan on SDC-1 (ng/mL) levels from blood derived from varicose veins at baseline (T0) and after 90 days of treatment (T1). Each line of the multiple-line chart represents each of the 23 patients involved in this study. A statistically significant decrease in SDC-1 values can be observed (157.1 [140.5–179.4] ng/mL at T1 vs. 187.4 [167.2–235.7] ng/mL at T0; p = 0.0005). Statistical analysis was performed using a paired Wilcoxon test and p < 0.05 was considered statistically significant.

Figure 6

Linear graph representing the effects of mesoglycan on SDC-4 (ng/mL) levels from blood derived from varicose veins at baseline (T0) and after 90 days of treatment (T1). Each line of the multiple-line chart represents each of the 23 patients involved in this study. A statistically significant decrease in SDC-4 values can be observed (42.22 [34.56–53.72] ng/mL at T1 vs. 56.75 [46.04–71.71] ng/mL at T0; p = 0.0002). Statistical analysis was performed using a paired Wilcoxon test and p < 0.05 was considered statistically significant.