RGD Reference Report - Olmesartan ameliorates pressure overload-induced cardiac remodeling through inhibition of TAK1/p38 signaling in mice. - Rat Genome Database

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Olmesartan ameliorates pressure overload-induced cardiac remodeling through inhibition of TAK1/p38 signaling in mice.

Authors: Wu, Lianpin  Mei, Liqin  Chong, Lin  Huang, Yinqing  Li, Yuechun  Chu, Maoping  Yang, Xiangjun 
Citation: Wu L, etal., Life Sci. 2016 Jan 15;145:121-6. doi: 10.1016/j.lfs.2015.12.034. Epub 2015 Dec 17.
RGD ID: 155791673
Pubmed: PMID:26706286   (View Abstract at PubMed)
DOI: DOI:10.1016/j.lfs.2015.12.034   (Journal Full-text)


AIMS: Many studies have demonstrated the potent effects of ARB administration on heart failure. However, the mechanism of the potent effects of ARB on cardiac remodeling is less well understood. We investigated the role of Olmesartan on the fibrosis and hypertrophy in mouse heart.
MATERIALS AND METHODS: We employed TAC surgery, a mouse model of chronic cardiac failure. All the mice were separated into three groups: the sham group, TAC group and TAC plus Olmesartan group (given Olmesartan treatment after TAC). We analyzed left ventricle remodeling, and function by echocardiography or pathology. We further detected the level of marker genes involved in fibrosis and hypertrophy and in cultured neonatal rat cardiac fibroblasts and myocytes infected by constitutively active TAK1 and p38MAPK. After TAC, all the mice developed hypertrophy, worse cardiac function and malignant remodeling in left ventricle.
KEY FINDINGS: Olmesartan improved heart remodeling and function without changing pressure of blood. Moreover, Olmesartan reduced the level of transforming growth factor β activated kinase-1 (TAK1) and phospho-p38MAPK. In neonatal rat cardiac fibroblast cells and cardiomyocytes, Olmesartan also decreased TAK1 and p38MAPK activation triggered by TGFβ1 or AngII. The inhibitory effect of Olmesartan was abrogated by overexpression of constitutively active TAK1 and p38MAPK by adenovirus system.
SIGNIFICANCE: Our results suggest Olmesartan improves heart remodeling and function induced by pressure overload. P38MAPK inactivation attenuated by olmesartan via inhibition of TAK1 pathway plays an important role in the process.




  
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Original Reference(s)
MAP3K7Humancongestive heart failure treatmentISOMap3k7 (Mus musculus) RGD 
Map3k7Ratcongestive heart failure treatmentISOMap3k7 (Mus musculus) RGD 
Map3k7Mousecongestive heart failure treatmentIEP  RGD 


  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
MAP3K7Humanolmesartan multiple interactionsISOMap3k7 (Rattus norvegicus)Olmesartan inhibits the reaction [Angiotensin II increases phosphorylation of Map3k7 protein in the heart]RGD 
Map3k7Ratolmesartan multiple interactionsEXP Olmesartan inhibits the reaction [Angiotensin II increases phosphorylation of Map3k7 protein in the heart]RGD 
Map3k7Mouseolmesartan multiple interactionsISOMap3k7 (Rattus norvegicus)Olmesartan inhibits the reaction [Angiotensin II increases phosphorylation of Map3k7 protein in the heart]RGD 


Genes (Rattus norvegicus)
Map3k7  (mitogen activated protein kinase kinase kinase 7)

Genes (Mus musculus)
Map3k7  (mitogen-activated protein kinase kinase kinase 7)

Genes (Homo sapiens)
MAP3K7  (mitogen-activated protein kinase kinase kinase 7)