Angiotensin (1-7)-Attenuated Vasoconstriction Is Associated With The Interleukin-10 Signaling Pathway

Angiotensin (1-7)-Attenuated Vasoconstriction Is Associated With The Interleukin-10 Signaling Pathway

• Autor
• Rainy Alves de Freitas
• Co-autores
• Rinaldo Rodrigues dos Pasos Junior , Vanessa Dela Justina , Alecsander Fabricio Bressan , Fernando da Silva Carneiro , Fernanda Regina Giachini , Victor Vitorino Lima
• Resumo

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  Introduction: Angiotensin-1-7 [Ang-(1-7)] is an essential peptide of the renin-angiotensin system that promotes benefits modulating effects in different tissues. Similarly, interleukin-10 (IL-10) exhibits an immunomodulatory action on the vasculature. This study aimed to evaluate whether Ang-(1-7) levels attenuates vascular contractile response, mediated by IL-10-pathway (JAK1/STAT3/IL-10). Methods: Male mice C57BL/6J and IL-10 knockout, aged 8-12 weeks and 25-30 grams, were used. Aortic segments were incubated with Ang-(1-7) [10 ?M] or vehicle, during 5 min, 1 h, 6 h, 12 h, and 24 h (n= 5-6 per group). Concentration-response curves to phenylephrine, western blotting, and flow cytometry analysis was performed to evaluate the contractile response, protein expression, and IL-10 levels, respectively. The statistics were determined by the Student t test or One-Way ANOVA test and Tukey's post-test. Approval by the Ethics Committee (CEUA USP - 014/2019). Results: Incubation with Ang-(1-7) produced a time-dependent increase in Janus kinases 1 (JAK1) expression, as well as increased expression and activity of the signal transducer and activator of transcription 3 (STAT3) protein. In vascular function, Ang- (1-7) reduced phenylephrine-induced vasoconstriction, at 5 min (7,45 ± 0,55 vs. 6,0 ± 0,76) and 12 h (9,33 ± 0,10 vs. 7,35 ± 0,15), but these effects were not observed in the endogenous absence of IL-10. Additionally, incubation with Ang-(1-7) augments IL-10 levels after 6 h, 12 h, and 24 hours of incubation. Conclusion: These results demonstrated the role of Ang-(1-7) in the IL-10 signaling pathway and its effects in the vascular contractility response. Thus, these findings suggest a new synergic action where Ang-(1-7) and IL-10 converge into a protective mechanism against vascular dysfunction.

• Palavras-chave
• Ang-(1-7), Renin-angiotensin system, Cytokines anti-inflamatory
• Modalidade
• Comunicação oral
• Área Temática
• Sinalização celular