Cardioprotection Conferred by Sitagliptin Is Associated with Reduced Cardiac Angiotensin II/Angiotensin-(1-7) Balance in Experimental Chronic Kidney Disease

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorBERALDO, Juliana Isa
dc.contributor.authorBENETTI, Acaris
dc.contributor.authorBORGES-JUNIOR, Flavio Araujo
dc.contributor.authorARRUDA-JUNIOR, Daniel F.
dc.contributor.authorMARTINS, Flavia Leticia
dc.contributor.authorJENSEN, Leonardo
dc.contributor.authorDARIOLLI, Rafael
dc.contributor.authorSHIMIZU, Maria Heloisa
dc.contributor.authorSEGURO, Antonio C.
dc.contributor.authorLUCHI, Weverton M.
dc.contributor.authorGIRARDI, Adriana C. C.
dc.date.accessioned2019-06-26T17:28:19Z
dc.date.available2019-06-26T17:28:19Z
dc.date.issued2019
dc.description.abstractDipeptidyl peptidase IV (DPPIV) inhibitors are antidiabetic agents that exert renoprotective actions independently of glucose lowering. Cardiac dysfunction is one of the main outcomes of chronic kidney disease (CKD); however, the effects of DPPIV inhibition on cardiac impairment during CKD progression remain elusive. This study investigated whether DPPIV inhibition mitigates cardiac dysfunction and remodeling in rats with a 5/6 renal ablation and evaluated if these effects are associated with changes in the cardiac renin-angiotensin system (RAS). To this end, male Wistar rats underwent a 5/6 nephrectomy (Nx) or sham operation, followed by an 8-week treatment period with the DPPIV inhibitor sitagliptin (IDPPIV) or vehicle. Nx rats had lower glomerular filtration rate, overt albuminuria and higher blood pressure compared to sham rats, whereas CKD progression was attenuated in Nx + IDPPIV rats. Additionally, Nx rats exhibited cardiac hypertrophy and fibrosis, which were associated with higher cardiac DPPIV activity and expression. The sitagliptin treatment prevented cardiac fibrosis and mitigated cardiac hypertrophy. The isovolumic relaxation time (IRVT) was higher in Nx than in sham rats, which was suggestive of CKD-associated-diastolic dysfunction. Sitagliptin significantly attenuated the increase in IRVT. Levels of angiotensin II (Ang II) in the heart tissue from Nx rats were higher while those of angiotensin-(1-7) Ang-(1-7) were lower than that in sham rats. This cardiac hormonal imbalance was completely prevented by sitagliptin. Collectively, these results suggest that DPPIV inhibition may delay the onset of cardiovascular impairment in CKD. Furthermore, these findings strengthen the hypothesis that a crosstalk between DPPIV and the renin-angiotensin system plays a role in the pathophysiology of cardiorenal syndromes.eng
dc.description.indexMEDLINEeng
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2013/10619-8, 2016/22140-7]
dc.identifier.citationINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.20, n.8, article ID 1940, 18p, 2019
dc.identifier.doi10.3390/ijms20081940
dc.identifier.issn1422-0067
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/32437
dc.language.isoeng
dc.publisherMDPIeng
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright MDPIeng
dc.subjectdipeptidyl peptidase IVeng
dc.subject5eng
dc.subject6 renal ablationeng
dc.subjectrenin-angiotensin systemeng
dc.subjectcardiorenal syndromeseng
dc.subject.otherdipeptidyl peptidase-iveng
dc.subject.otherglucagon-like peptide-1eng
dc.subject.othercardiovascular outcomeseng
dc.subject.otherinhibitor linagliptineng
dc.subject.otheraldosterone systemeng
dc.subject.otherheart-failureeng
dc.subject.otherdysfunctioneng
dc.subject.otherexpressioneng
dc.subject.otherprotectseng
dc.subject.otherprogressioneng
dc.subject.wosBiochemistry & Molecular Biologyeng
dc.subject.wosChemistry, Multidisciplinaryeng
dc.titleCardioprotection Conferred by Sitagliptin Is Associated with Reduced Cardiac Angiotensin II/Angiotensin-(1-7) Balance in Experimental Chronic Kidney Diseaseeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.citation.scopus23
hcfmusp.contributor.author-fmusphcJULIANA ISA BERALDO
hcfmusp.contributor.author-fmusphcACARIS BENETTI DOS SANTOS
hcfmusp.contributor.author-fmusphcFLAVIO ARAUJO BORGES JUNIOR
hcfmusp.contributor.author-fmusphcDANIEL FRANCISCO DE ARRUDA JUNIOR
hcfmusp.contributor.author-fmusphcFLAVIA LETICIA MARTINS
hcfmusp.contributor.author-fmusphcLEONARDO JENSEN SOCAS
hcfmusp.contributor.author-fmusphcRAFAEL DARIOLLI
hcfmusp.contributor.author-fmusphcMARIA HELOISA MASSOLA SHIMIZU
hcfmusp.contributor.author-fmusphcANTONIO CARLOS SEGURO
hcfmusp.contributor.author-fmusphcWEVERTON MACHADO LUCHI
hcfmusp.contributor.author-fmusphcADRIANA CASTELLO COSTA GIRARDI
hcfmusp.description.articlenumber1940
hcfmusp.description.issue8
hcfmusp.description.volume20
hcfmusp.origemWOS
hcfmusp.origem.pubmed31010001
hcfmusp.origem.scopus2-s2.0-85065115876
hcfmusp.origem.wosWOS:000467648700138
hcfmusp.publisher.cityBASELeng
hcfmusp.publisher.countrySWITZERLANDeng
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