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Aliskiren inhibits the renin-angiotensin system in retinal pigment epithelium cells

2016-09Journal article Restricted access
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dc.contributor.authorS, Simão
dc.contributor.authorSantos, Daniela F.
dc.contributor.authorSilva, Gabriela
dc.date.accessioned2017-04-07T15:56:01Z
dc.date.available2017-04-07T15:56:01Z
dc.date.issued2016-09
dc.description.abstractObservations of increased angiotensin II levels and activation of the (pro)renin receptor in retinopathies support the role of ocular renin-angiotensin system (RAS) in the development of retinal diseases. While targeting RAS presents significant therapeutic potential, current RAS-based therapies are ineffective halting the progression of these diseases. A new class of drugs, the direct renin inhibitors such as aliskiren, is a potential therapeutic alternative. However, it is unclear how aliskiren acts in the retina, in particular in the retinal pigment epithelium (RPE), the structure responsible for the maintenance of retinal homeostasis whose role is deeply compromised in retinal diseases. We firstly analyzed the expression and activity of the main RAS components in RPE cells. Time- and concentration-dependent treatments with aliskiren were performed to modulate different pathways of the RAE in RPE cells. Our data demonstrate that RPE cells express the main RAS constituents. Exposure of RPE cells to aliskiren inhibited the activity of renin and consequently decreased the levels of angiotensin II. Additionally, aliskiren reduced the translocation of the (pro)renin receptor to the cellular membrane of RPE cells preventing the activation of ERK1/2.Our findings of the RPE well-defined RAS, together with the demonstration that aliskiren effectively blocks this system at different steps of the cascade, suggest that aliskiren might be an alternative and successful drug in preventing the deleterious effects derived from the overactivation of the RAS, known to contribute to the pathogenesis of different retinal diseases. (C) 2016 Elsevier B.V. All rights reserved.
dc.description.sponsorshipPIRG05-GA-2009-249314; EXPLBIM-MEC-1433-2013
dc.identifier.doihttps://doi.org/10.1016/j.ejps.2016.06.019
dc.identifier.issn0928-0987
dc.identifier.otherAUT: GAS02236;
dc.identifier.urihttp://hdl.handle.net/10400.1/9290
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.relationTowards a therapy for diabetic retinopathy: RAS and Berries
dc.relation.isbasedonWOS:000381833900003
dc.subjectRetinal pigment epithelium cells
dc.subjectAliskiren
dc.subjectRenin-angiotensin system
dc.subjectProrenin receptor
dc.titleAliskiren inhibits the renin-angiotensin system in retinal pigment epithelium cells
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleTowards a therapy for diabetic retinopathy: RAS and Berries
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F78404%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F114251%2F2016/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F04773%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04462%2F2013/PT
oaire.citation.endPage27
oaire.citation.startPage22
oaire.citation.titleEuropean Journal of Pharmaceutical Sciences
oaire.citation.volume92
oaire.fundingStreamSFRH
oaire.fundingStream5876
oaire.fundingStream5876
person.familyNameSimao
person.givenNameSonia
person.identifier.orcid0000-0002-0245-0633
person.identifier.scopus-author-id24067982400
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccess
rcaap.typearticle
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