The angiotensin-(1-7)/mas axis counteracts angiotensin II-dependent and -independent pro-inflammatory signaling in human vascular smooth muscle cells
EntidadUAM. Departamento de Farmacología; UAM. Departamento de Medicina; Instituto de Investigación del Hospital de La Princesa (IP)
Fecha de edición2016-01-01
10.3389/fphar.2016.00482Frontiers in Pharmacology 7 (2016): Article 482
Financiado porThis work was funded by grants from Ministerio de Economía y Competitividad (SAF2014-52762-R)
ProyectoGobierno de España. SAF2014-52762-R
Versión del editorhttp://dx.doi.org/10.3389/fphar.2016.00482
MateriasAngiotensin-(1-7); Cell signaling; Cytokines; Inducible nitric oxide synthase; Inflammation; Interleukin-1β; Mas receptors; Vascular smooth muscle; Medicina
Derechos© 2016 Villalobos, San Hipólito-Luengo, Ramos-González, Cercas, Vallejo, Romero, Romacho, Carraro, Sánchez-Ferrer and Peiró.
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
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.
Google Scholar:Villalobos, Laura A. - San Hipólito-Luengo, Álvaro - Ramos-González, Mariella - Cercas, Elena - Vallejo, Susana - Romero, Alejandra - Romacho, Tania - Carraro, Raffaele
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The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation Romero, Alejandra; San Hipólito-Luengo, Álvaro; Villalobos, Laura A.; Vallejo, Susana; Valencia, Inés; Michalska, Patrycja; Pajuelo-Lozano, Natalia; Sánchez Pérez, María Isabel; León, Rafael; Bartha Rasero, José Luis; Sanz, María Jesús; Erusalimsky, Jorge D.; Sánchez Ferrer, Carlos Félix; Romacho, Tania; Peiró Vallejo, M. Concepción