The angiotensin-(1-7)/mas axis counteracts angiotensin II-dependent and -independent pro-inflammatory signaling in human vascular smooth muscle cells
Entity
UAM. Departamento de Farmacología; UAM. Departamento de Medicina; Instituto de Investigación del Hospital de La Princesa (IP)Publisher
Frontiers MediaDate
2016-01-01Citation
10.3389/fphar.2016.00482
Frontiers in Pharmacology 7 (2016): Article 482
ISSN
1663-9812DOI
10.3389/fphar.2016.00482Funded by
This work was funded by grants from Ministerio de Economía y Competitividad (SAF2014-52762-R)Project
Gobierno de España. SAF2014-52762-REditor's Version
http://dx.doi.org/10.3389/fphar.2016.00482Subjects
Angiotensin-(1-7); Cell signaling; Cytokines; Inducible nitric oxide synthase; Inflammation; Interleukin-1β; Mas receptors; Vascular smooth muscle; MedicinaRights
© 2016 Villalobos, San Hipólito-Luengo, Ramos-González, Cercas, Vallejo, Romero, Romacho, Carraro, Sánchez-Ferrer and Peiró.Abstract
Background and Aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7) is a member of the renin-angiotensin system (RAS) that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7) to counteract human aortic smooth muscle cell (HASMC) inflammation triggered by RAS-dependent and -independent stimuli, such as Ang II or interleukin (IL)-1β. Methods and Results: In cultured HASMC, the expression of inducible nitric oxide synthase (iNOS) and the release of nitric oxide were stimulated by both Ang II and IL-1β, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7) in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro7-Ang-(1-7), suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and nuclear factor (NF)-κB. Indeed, Ang-(1-7) markedly inhibited the activation of the NADPH oxidase and subsequently of NF-κB, as determined by lucigenin-derived chemiluminescence and electromobility shift assay, respectively. Conclusion: Ang-(1-7) can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7)/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases.
Files in this item
Google Scholar:Villalobos, Laura A.
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San Hipólito-Luengo, Álvaro
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Ramos-González, Mariella
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Cercas, Elena
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Vallejo, Susana
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Romero, Alejandra
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Romacho, Tania
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Carraro, Raffaele
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