Study of heparan sulfate proteoglycan, a marker of endothelial dysfunction in medical workers(pilotstudy)

Endothelial dysfunction (ED) is a universal developmental mechanism of most diseases of various body systems, characterized by a decrease in vasodilation and the development of proinflammatory and prothrombotic conditions. Impaired vasodilation is primarily associated with a decrease in production and bioavailability of endogenous nitric oxide (NO). One of the methods for ED assessment is measuring the level of markers of its damage in blood serum, such as homocysteine (HCYS), monocyte chemotactic protein‑1 (MCP‑1), proteins of vascular endothelial growth factor (VEGF) family, and many others with low diagnostic effectiveness. In recent years, a number of studies have shown a reliable association between the level of Heparan Sulfate Proteoglycan (hHSPG) and endothelial damage in various acute and chronic diseases.

The purpose of the study. To perform a pilot study of hHSPG levels in comparison with other biomarkers of endothelial damage in blood serum and to identify the correlation of their levels with blood flow rates and endothelial function in microcirculatory system and large vessels in healthy medical workers.

Material and methods. The study involved healthy male medical workers (n=21). The levels of hHSPG, HCYS, MCP‑1, VEGF‑A in blood serum were measured by enzyme immunoassay. According to the results of the study, two groups were formed – an experimental group (n=6) with a significant increase in hHSPG level and a control group (n=15) with a normal level of this marker. In these groups blood flow and endothelial function were assessed using bulbar conjunctival capillaroscopy, laser Doppler flowmetry (LDF) of the skin and photoplethysmographic examination of upper extremity vessels.

The results of the study. In experimental group a high level of hHSPG was detected, exceeding the upper reference range for this marker by more than 2 times to values of 26.6 [24.775; 28.15] ng/ml compared with the control group, where the level of this marker was 4.879 [3.84; 6.944] ng/ml (p=0.001). In addition, there was a tendency in MCP‑1 marker increase in experimental group – 201.96 [91.9; 220.2] pg/ml compared with the control group 104.91 [72.62;127.67] pg/ml (p=0.052). Correlation analysis of hHSPG with markers HCYS, MCP‑1, VEGF‑A showed a strong positive association between hHSPG and MCP‑1 (r_s=0.746), as well as between HCYS and VEGF‑A (r_s=0.436) and between MCP‑1 and VEGF‑A (r_s=0,286). According to the results of blood circulation instrumental study a significant difference in the characteristics of capillary blood flow between the groups was revealed: a decrease in capillary density (10,15 [2.57; 11.60]% in main and 14.90 [10.90; 17.00]% in control (p=0.018)) in bulbar conjunctival microscopy, as well as decrease in capillary bed perfusion (6.80 [5.39; 15.98] in main and 25.02 [18.9; 32.98] in control (p=0.005)) and decreased endothelial function (0.14 [0.02; 0.31] in main and 0.76 [0.55; 1.04] in control (p=0.002)) in LDF. In plethysmographic examination there were no differences in arterial stiffness index (SI) and reflection index (RI). Correlation analysis of laboratory and instrumental ED parameters showed the presence of a moderate inverse relationship between the level of Heparan Sulfate Proteoglycan and endothelial function (Ae) measured by LDF (p=0.024, r_s= –0.491).

Conclusion. An increase in Heparan Sulfate Proteoglycan is a promising marker of ED at the initial stage of its development in microcirculatory system.

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