Orientadora: Profa. Dra.Marcela Sorelli Carneiro Ramos / Tese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Biossistemas, 2015. / Recentemente, dados na literatura demonstram a estreita interacao patofisiologica existente entre os rins e o coracao. Conhecida como sindrome cardio-renal, essa patologia e capaz de promover hipertrofia e falencia cardiaca a partir de um quadro de lesao renal. Sabe-se que a lesao renal isquemica (LRI) promove a liberacao de diferentes citocinas inflamatorias que tem o coracao como tecido alvo e sao capazes de promover a instalacao do quadro hipertrofico, agindo, por exemplo, por meio de receptores semelhantes ao Toll (toll-like receptors - TLR). Alem de mediadores inflamatorios, trabalhos presentes na literatura ja comprovaram a direta relacao entre alteracoes no sistema renina-angiotensina (SRA) e nos niveis de Angiotensina II (Ang II) com o aumento da massa cardiaca. O presente estudo objetivou investigar o papel do SRA com a hipertrofia cardiaca (HC) induzida por um modelo experimental de LRI em camundongos tratados ou nao com bloqueadores do SRA, Losartan (Los) e Enalapril (Ena). O quadro de LRI foi induzido cirurgicamente atraves da oclusao do pediculo renal esquerdo por 60 minutos seguido de reperfusao. Apos 12, 15 ou 20 dias os tecidos foram removidos para a realizacao de analises macromorfometricas, moleculares e funcionais. Os principais resultados indicam que a cirurgia de isquemia renal e reperfusao foi capaz de gerar um quadro de falencia renal e induzir HC de maneira independente de aumento na pressao arterial. Ainda, no periodo analisado, observou-se aumento nos niveis sericos de TNF-¿¿ e Ang II, elevados niveis de expressao genica ou proteica de AT1, ECA-2, TLR-2, TLR-4 e NFk¿À, sugerindo relacao
desses componentes com a HC. Os tratamentos com Los e Ena reverteram completamente a HC observada e aboliram o aumento na expressao cardiaca de TLRs, AT1R e ECA-2 e modularam diferencialmente os niveis sericos de Ang II e citocinas inflamatorias. Juntos, os dados sugerem um papel crucial do SRA na regulacao do quadro patologico neste modelo,
atuando juntamente com o sistema imune inato na regulacao da patogenese da HC atraves da modulacao de seus principais componentes. / Recently published data demonstrate the close pathophysiological interaction
between the kidneys and the heart. Known as cardio-renal syndrome, this
pathology is capable of promoting hypertrophy and heart failure starting from
renal injury. It is known that ischemic renal injury (IRI) promotes the release
of various inflammatory cytokines that have the heart as a target tissue and
are capable of promoting hypertrophy acting through the Toll-like receptors
(TLR). In addition to inflammatory mediators, literature has extensively
demonstrated the direct correlation between changes in the renin-angiotensin
system (RAS) and the levels of angiotensin II (Ang II) within the increase in
cardiac mass. This study aimed to investigate the role of the RAS with
cardiac hypertrophy (CH) induced by an experimental model of IRI in mice
treated or not with RAS blockers, Losartan (Los) and Enalapril (Ena). The IRI
was surgically induced by occlusion of the left renal pedicle for 60 minutes
followed by reperfusion. After 12, 15 or 20 days, tissues were removed and
morphological, molecular, and functional analysis were performed. The
leading results indicate that renal ischemia and reperfusion surgery was
capable of generating renal failure which subsequently induced HC in a
blood-pressure independent manner. Also, over this period, there was an
increase in serum levels of TNF-á and Ang II, high levels of gene or protein
expression of AT1, ACE-2, TLR-2, TLR-4 and NFkâ, suggesting a cross-talk
within these components and CH development. Treatment with Los or Ena
has completely reversed the CH and abolished the increase observed in
cardiac expression of TLRs, NFkâ, ACE-2 and AT1R, and also differentially
modulated Ang II and inflammatory cytokines serum levels. Together, the
data suggest a critical role for RAS in the regulation of the pathological
condition in this model, acting together with the innate immune system in the
pathogenesis of CH through modulation of its main components.
| Identifer | oai:union.ndltd.org:IBICT/oai:BDTD:77246 |
| Date | January 2015 |
| Creators | Abrahão, Mariana Vieira |
| Contributors | Ramos, Marcela Sorelli Carneiro, Carrettiero, Daniel Carneiro, Santos Júnior, Arnaldo Rodrigues dos, Heimann, Joel Claudio, Diniz, Gabriela Placoná |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf, 212 f. : il. |
| Source | reponame:Repositório Institucional da UFABC, instname:Universidade Federal do ABC, instacron:UFABC |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | http://biblioteca.ufabc.edu.br/index.php?codigo_sophia=77246&midiaext=70613, http://biblioteca.ufabc.edu.br/index.php?codigo_sophia=77246&midiaext=70614, Cover: http://biblioteca.ufabc.edu.brphp/capa.php?obra=77246 |
Page generated in 0.0028 seconds