Ethanol consumption favors pro-contractile phenotype of perivascular adipose tissue: A role for interleukin-6

Author(s)

Simplicio, Janaina A. ; Dourado, Thales M. H. ; Awata, Wanessa M. C. ; do Vale, Gabriel T. ; Dias, Vinicius R. ; Barros, Paula R. ; de Martinis, Bruno S. ; Tostes, Rita C. ; Tirapelli, Carlos R.

• Document type: Journal article
• Source: Life Sciences; v. 319, p. 10-pg., 2023-03-03.

Abstract

Perivascular adipose tissue (PVAT) exerts anticontractile effect, but under non-physiological conditions it may contribute to vascular dysfunction by releasing pro-inflammatory cytokines. Since PVAT is an important source of interleukin (IL)-6, we evaluated whether this cytokine would contribute to ethanol-induced vascular dysfunction. With this purpose, male C57BL/6 wild-type (WT) or IL-6-deficient mice (IL-6- /- )were treated with ethanol for 12 weeks. Increased blood pressure was evidenced after 4 and 6 weeks of treatment with ethanol in WT and IL-6-/-mice, respectively. In WT mice, ethanol increased plasma and PVAT levels of IL-6. Ethanol favoured pro-contractile phenotype of PVAT in mesenteric arteries from WT, but not IL-6-deficient mice. Functional studies showed that tiron [(a scavenger of superoxide (O2 center dot-)] reversed the pro-contractile effect of PVAT in mesenteric arteries from ethanol-treated mice. Ethanol increased the levels of O2-center dot in PVAT from WT mice. Ethanol-induced increase in O2-center dot generation was higher in arteries with PVAT from WT mice when compared to IL-6-deficient mice. Treatment with ethanol augmented myeloperoxidase activity in the mesenteric arterial bed (MAB; with or without PVAT) from WT, but not IL-6-deficient mice. In conclusion, IL-6 contributes to the pro-contractile effect of PVAT by a mechanism that involves increase in ROS generation. Additionally, IL-6 mediates intravascular recruitment of neutrophils in response to ethanol and plays a role in the early stages of ethanol-induced hypertension. Collectively, our findings provide novel evidence for a role of IL-6 in the vascular dysfunction induced by ethanol. (AU)

• FAPESP's process: 19/25189-5 - Effect of chronic ethanol consumption on the modulatory action displayed by perivascular adipose tissue: a role for angiotensin II
• Grantee: Carlos Renato Tirapelli
• Support Opportunities: Regular Research Grants