Systemic factors regulating of angiogenesis in multiple uterine fibroids

Abstract

Uterine leiomyomas (LM), or uterine fibroids (UF), are benign tumors of the uterus. Hypertrophic increase in muscle mass in LM is accompanied by the development of appropriate vascular networks, which are regulated by the balance of proangiogenic factors, one of which is VEGF-A. In addition, a number of inflammatory molecules have the proangiogenic effect, the most significant of which are IL-1b, IL-8, etc. Each of the cytokines or growth factors has its own control and regulatory functions. The spectrum of their activity may overlap and be regulated by other cytokines. The Aim: to assess the concentration of cytokines actively involved in the regulation of vascular network growth in the peripheral blood of patients with multiple uterine fibroids in comparison with data from a group conditionally healthy women. Methods: The survey included 178 women: 89 women (23-60 years old) with uterine fibroids and 89 conditionally healthy women of the same age (22-61 years old). The levels of TNF-α, IL-1β, IL-4, IL-6, IL-8, IL-10 and VEGF-A were detected by the ELISA method using the Vector-Best test systems (Russia). The optical density of the solutions was measured at a wavelength of 450 nm. Statistical analysis was carried out using the IBM SPSS Statistics 23 (USA). The results: Serum levels of cytokines with proinflammatory activity IL-6 and TNFa, as well as chemokine IL-8, were significantly higher among patients compared with healthy women. The serum level of VEGF in both healthy women and patients with LM is represented by three-digit values. The dependence of the VEGF level and the number of myomatous nodes identified and surgically removed has been established. With multiple detected nodes (more than two), the VEGF serum level is significantly higher than with the detection of a single node. According to the data obtained, the IL-6, IL-8 and TNFa serum levels in patients with multiple myomatous nodes also slightly exceeds the values of this indicator in the group of women with single nodes (p>0.05). In healthy women, an increase in TNF-α level is directly correlated with an increase of IL-6 serum level. Along with this, the correlation with the VEGF level is slightly negative. In leiomyoma, the nature of these relationships persists: for the IL-6, IL-8, VEGF level. Both among patients with single and multiple nodes, the pattern of correlation relations remain unchanged. Conclusion: The obtained data are of practical importance not only as a basis for the development of prognostic criteria for the development of MM at the preclinical stage, but also as differential diagnostic additional laboratory signs. In particular, when differentiating uterine leiomyoma, the most common benign myomatous tumor of the uterus, from malignant uterine leiomyosarcomas.

Keywords

• uterine fibroids
• enzyme-linked immunosorbent assay
• tnf-a
• il-1
• il-4
• l-6
• il-8
• il-10
• vegf