Papel da interleucina-10 na morfologia vascular e como mediadora do efeito anti-contrátil do tecido adiposo perivascular

Abstract

Arteries are important blood vessels responsible for transporting cells and nutrients to all cells and tissues in the body. For its correct correction, an adequate structure and vascular composition is necessary, such as endothelial and flexible layers, collagen and elastic fibers, and vasoactive mediators. Structural changes can alter vascular changes and alter problems. Surrounding the vasculature is perivascular adipose tissue (PVAT), which provides vessel protection, heat and energy. However, studies have shown a broader role through the secretion of bioactive substances that can exert local or systemic effects, including an anti-contractile effect and the regulation of vascular tone. Interleukin-10 (IL-10), an anti-inflammatory and immunomodulatory cytokine, has been shown to be able to modulate different vascular function responses. However, the role of this cytokine in vascular morphology and as a possible mediator of the anti-contractile effect of PVAT has not yet been elucidated. Thus, the aim of the present study was to evaluate the effect of IL-10 on vascular tissue morphology in the face of vascular remodeling and as a mediator of the anti-contractile effect exerted by PVAT. For this, 6-8 male mice of the C57BL/6J strain [wild, (WT)] and IL-10 knockout [B6.12P2-Il10tm1Cgn/J (IL-10-/-)] were used, with 8- 12 weeks of age, from that date the animals were euthanized to remove the aortic segments. Thoracic aortic segments were submitted to histological analysis for staining with hematoxylin-eosin, picrosirius and resorcin, to evaluate parameters of vascular structures, collagen deposition and elastic fibers, respectively. Aortic segments with the presence and absence of tissue PVAT were used to analyze vascular reactivity in order to evaluate the contractile effects induced by phenylephrine (1 nM to 100 μM). The methodology was approved by the Animal Use Ethics Committee (014/2019). The statistical significance of the data was determined using Student's t test or One Way ANOVA test followed by Tukey's post-test. It was observed that the absence of endogenous IL-10 promoted changes in vascular morphology, such as a reduction in the PVAT area (0.54 ± 0.08 vs. 0.28 ± 0.02 in mm2), an increase in the area (0.14 ± 0.014 vs. 0.19 ± 0.014 in mm2) and vessel thickness (0.032 ± 0.001 vs. 0.045 ± 0.001 in mm2), increased percentage of collagen deposition (40.22 ± 4.53 vs. 66.30 ± 7.16 in %) and reduction of elastic fiber deposition (67.20 ± 3.21 vs. 54.95 ± 3.69 in %). In vascular function, the presence of PVAT prevented the increase in vascular contraction in control animals (7.641 ± 0.858 vs. 5.014 ± 0.418 in %). On the other hand, IL-10-/- animals showed a greater contractile response compared to the control group (7.641 ± 0.858 vs. 10.026 ± 1.324 in %), but the presence of PVAT was not able to exert its anti-contractile effect in the absence of endogenous IL-10. Thus, endogenous IL-10 has been shown to be able to prevent vascular remodeling and mediate the anti-contractile effect of PVAT in aortic tissue. Therefore, these results demonstrate the importance of IL-10 and its role in the vasculature, indicating a possible future therapeutic target for the treatment of cardiovascular diseases.