Reduced Plasma Angiotensin Ii Levels Are Reversed By Hydroxyurea Treatment In Mice With Sickle Cell Disease.

dc.creatordos Santos, Alisson F
dc.creatorAlmeida, Camila B
dc.creatorBrugnerotto, Ana F
dc.creatorRoversi, Fernanda M
dc.creatorPallis, Flávia R
dc.creatorFranco-Penteado, Carla F
dc.creatorLanaro, Carolina
dc.creatorAlbuquerque, Dulcinéia M
dc.creatorLeonardo, Flávia C
dc.creatorCosta, Fernando F
dc.creatorConran, Nicola
dc.date2014-Nov
dc.date2015-11-27T13:43:22Z
dc.date2015-11-27T13:43:22Z
dc.date.accessioned2018-03-29T01:22:01Z
dc.date.available2018-03-29T01:22:01Z
dc.identifierLife Sciences. v. 117, n. 1, p. 7-12, 2014-Nov.
dc.identifier1879-0631
dc.identifier10.1016/j.lfs.2014.08.021
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/25219880
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/201723
dc.identifier25219880
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1301956
dc.descriptionSickle cell disease (SCD) pathogenesis leads to recurrent vaso-occlusive and hemolytic processes, causing numerous clinical complications including renal damage. As vasoconstrictive mechanisms may be enhanced in SCD, due to endothelial dysfunction and vasoactive protein production, we aimed to determine whether the expression of proteins of the renin-angiotensin system (RAS) may be altered in an animal model of SCD. Plasma angiotensin II (Ang II) was measured in C57BL/6 (WT) mice and mice with SCD by ELISA, while quantitative PCR was used to compare the expressions of the genes encoding the angiotensin-II-receptors 1 and 2 (AT1R and AT2R) and the angiotensin-converting enzymes (ACE1 and ACE2) in the kidneys, hearts, livers and brains of mice. The effects of hydroxyurea (HU; 50-75mg/kg/day, 4weeks) treatment on these parameters were also determined. Plasma Ang II was significantly diminished in SCD mice, compared with WT mice, in association with decreased AT1R and ACE1 expressions in SCD mice kidneys. Treatment of SCD mice with HU reduced leukocyte and platelet counts and increased plasma Ang II to levels similar to those of WT mice. HU also increased AT1R and ACE2 gene expression in the kidney and heart. Results indicate an imbalanced RAS in an SCD mouse model; HU therapy may be able to restore some RAS parameters in these mice. Further investigations regarding Ang II production and the RAS in human SCD may be warranted, as such changes may reflect or contribute to renal damage and alterations in blood pressure.
dc.description117
dc.description7-12
dc.languageeng
dc.relationLife Sciences
dc.relationLife Sci.
dc.rightsfechado
dc.rightsCopyright © 2014 Elsevier Inc. All rights reserved.
dc.sourcePubMed
dc.subjectAnemia, Sickle Cell
dc.subjectAngiotensin Ii
dc.subjectAnimals
dc.subjectDisease Models, Animal
dc.subjectDose-response Relationship, Drug
dc.subjectEnzyme-linked Immunosorbent Assay
dc.subjectGene Expression Regulation
dc.subjectHydroxyurea
dc.subjectKidney
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred C57bl
dc.subjectMice, Transgenic
dc.subjectPeptidyl-dipeptidase A
dc.subjectReal-time Polymerase Chain Reaction
dc.subjectReceptor, Angiotensin, Type 1
dc.subjectReceptor, Angiotensin, Type 2
dc.subjectRenin-angiotensin System
dc.subjectAngiotensin Ii
dc.subjectKidneys
dc.subjectRenin–angiotensin System
dc.subjectSickle Cell Disease
dc.subjectVasoconstriction
dc.titleReduced Plasma Angiotensin Ii Levels Are Reversed By Hydroxyurea Treatment In Mice With Sickle Cell Disease.
dc.typeArtículos de revistas


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