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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

MAS receptors mediate vasoprotective and atheroprotective effects of candesartan upon the recovery of vascular angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis functionality

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Author(s):
Pernomian, Larissa [1] ; do Prado, Alejandro F. [2] ; Gomes, Mayara S. [3] ; Pernomian, Laena [2] ; da Silva, Carlos H. T. P. [1] ; Gerlach, Raquel F. [4] ; de Oliveira, Ana M. [3]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto FCFRP, Dept Pharmaceut Sci, BR-14049 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pharmacol, Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, FCFRP, Dept Chem & Phys, Ribeirao Preto, SP - Brazil
[4] Univ Sao Paulo, Fac Odontol Ribeirao Preto FORP, Dept Morphol, Ribeirao Preto, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: European Journal of Pharmacology; v. 764, p. 173-188, OCT 5 2015.
Web of Science Citations: 11
Abstract

AT(1) antagonists effectively prevent atherosclerosis since AT(1) upregulation and angiotensin II-induced proinflammatory actions are critical to atherogenesis. Despite the classic mechanisms underlying the vasoprotective and atheroprotective actions of AT(1) antagonists, the cross talk between angiotensin-converting enzyme-angiotensin II-AT(1) and angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axes suggests other mechanisms beyond AT1. blockage in such effects. For instance, angiotensin-converting enzyme 2 activity is inhibited by reactive oxygen species derived from AT(1)-mediated proinflammatory signaling. Since angiotensin-(1-7) promotes antiatherogenic effects, we hypothesized that the vasoprotective and atheroprotective effects of AT(1) antagonists could result from their inhibitory effects on the AT(1)-mediated negative modulation of vascular angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis functionality, interestingly, our results showed that early atherosclerosis triggered in thoracic aorta from high cholesterol fed-Apolipoprotein E-deficient mice impairs angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis functionality by a prointlammatory-redox AT(1)-mediated pathway, in such mechanism, AT(1) activation leads to the aortic release of tumor necrosis factor-alpha which stimulates NAD(P)H oxidase/Nox1-driven generation of superoxide and hydrogen peroxide. While hydrogen peroxide inhibits angiotensin-converting enzyme 2 activity, superoxide impairs MAS functionality. Candesartan treatment restored the functionality of angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis by inhibiting the proinflammatory-redox AT(1)-mediated mechanism. Candesartan also promoted vasoprotective and atheroprotective effects that were mediated by MAS since A779 (MAS antagonist) co-treatment inhibited them. The role of MAS receptors as the final mediators of the vasoprotective and atheroprotective effects of candesartan was supported by the vascular actions of angiotensin-(1-7) upon the recovery of the functionality of vascular angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis. (C) 2015 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 12/00640-7 - Study of the consequences of the inflammatory process induced by AT1 receptors during atherosclerosis on the ACE2 - angiotensin-(1-7) - Mas axis in mouse aorta and the involvement of Mas receptors in the vaso- and atheroprotective effects of losartan
Grantee:Larissa Pernomian
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 14/17740-0 - Planning, development and pharmacological evaluation of new aryl hydrocarbon receptors (AhR) antagonists that are candidates for atheroprotective drugs
Grantee:Larissa Pernomian
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 12/09019-3 - Consequences of dyslipidemia on the ACE - Ang II - AT1 and ACE2 - Ang-(1-7) - mas axes from the angiotensinergic system in aorta from young and adult LDLr knockout mice
Grantee:Ana Maria de Oliveira
Support type: Regular Research Grants