RGD Reference Report - Aliskiren ameliorates pressure overload-induced heart hypertrophy and fibrosis in mice. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Aliskiren ameliorates pressure overload-induced heart hypertrophy and fibrosis in mice.

Authors: Weng, LQ  Zhang, WB  Ye, Y  Yin, PP  Yuan, J  Wang, XX  Kang, L  Jiang, SS  You, JY  Wu, J  Gong, H  Ge, JB  Zou, YZ 
Citation: Weng LQ, etal., Acta Pharmacol Sin. 2014 Aug;35(8):1005-14. doi: 10.1038/aps.2014.45. Epub 2014 Jul 7.
RGD ID: 11561938
Pubmed: PMID:24998254   (View Abstract at PubMed)
PMCID: PMC4125714   (View Article at PubMed Central)
DOI: DOI:10.1038/aps.2014.45   (Journal Full-text)

AIM: Aliskiren (ALK) is a renin inhibitor that has been used in the treatment of hypertension. The aim of this study was to determine whether ALK could ameliorate pressure overload-induced heart hypertrophy and fibrosis, and to elucidate the mechanisms of action. METHODS: Transverse aortic constriction (TAC) was performed in mice to induce heart pressure overload. ALK (150 mg.kg(-1).d(-1), po), the autophagy inhibitor 3-methyladenine (10 mg.kg(-1) per week, ip) or the PKCbetaI inhibitor LY333531 (1 mg.kg(-1).d-(1), po) was administered to the mice for 4 weeks. Heart hypertrophy, fibrosis and function were evaluated based on echocardiography, histological and biochemical measurements. Mechanically stretched cardiomyocytes of rats were used for in vitro experiments. The levels of signaling proteins were measured using Western blotting, while the expression of the relevant genes was analyzed using real-time QRT-PCR. RESULTS: TAC induced marked heart hypertrophy and fibrosis, accompanied by high levels of Ang II in plasma and heart, and by PKCbetaI/alpha and ERK1/2 phosphorylation in heart. Meanwhile, TAC induced autophagic responses in heart, i.e. increases in autophagic structures, expression of Atg5 and Atg16 L1 mRNAs and LC3-II and Beclin-1 proteins. These pathological alterations in TAC-mice were significantly ameliorated or blocked by ALK administration. In TAC-mice, 3-methyladenine administration also ameliorated heart hypertrophy, fibrosis and dysfunction, while LY333531 administration inhibited ERK phosphorylation and autophagy in heart. In mechanically stretched cardiomyocytes, CGP53353 (a PKCbetaI inhibitor) prevented ERK phosphorylation and autophagic responses, while U0126 (an ERK inhibitor) blocked autophagic responses. CONCLUSION: ALK ameliorates heart hypertrophy, fibrosis and dysfunction in the mouse model in setting of chronic pressure overload, via suppressing Ang II-PKCbetaI-ERK1/2-regulated autophagy.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ATG16L1HumanCardiomegaly treatmentISOAtg16l1 (Rattus norvegicus) RGD 
ATG5HumanCardiomegaly treatmentISOAtg5 (Rattus norvegicus) RGD 
Atg16l1RatCardiomegaly treatmentIEP  RGD 
Atg16l1MouseCardiomegaly treatmentISOAtg16l1 (Rattus norvegicus) RGD 
Atg5RatCardiomegaly treatmentIEP  RGD 
Atg5MouseCardiomegaly treatmentISOAtg5 (Rattus norvegicus) RGD 
BECN1HumanCardiomegaly treatmentISOBecn1 (Rattus norvegicus) RGD 
Becn1RatCardiomegaly treatmentIEP  RGD 
Becn1MouseCardiomegaly treatmentISOBecn1 (Rattus norvegicus) RGD 
MAP1LC3AHumanCardiomegaly treatmentISOMap1lc3a (Rattus norvegicus) RGD 
Map1lc3aRatCardiomegaly treatmentIEP  RGD 
Map1lc3aMouseCardiomegaly treatmentISOMap1lc3a (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Atg16l1  (autophagy related 16-like 1)
Atg5  (autophagy related 5)
Becn1  (beclin 1)
Map1lc3a  (microtubule-associated protein 1 light chain 3 alpha)

Genes (Mus musculus)
Atg16l1  (autophagy related 16 like 1)
Atg5  (autophagy related 5)
Becn1  (beclin 1, autophagy related)
Map1lc3a  (microtubule-associated protein 1 light chain 3 alpha)

Genes (Homo sapiens)
ATG16L1  (autophagy related 16 like 1)
ATG5  (autophagy related 5)
BECN1  (beclin 1)
MAP1LC3A  (microtubule associated protein 1 light chain 3 alpha)


Additional Information