RGD Reference Report - Mechanism of the inhibitory effect of atorvastatin on endoglin expression induced by transforming growth factor-beta1 in cultured cardiac fibroblasts. - Rat Genome Database

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Mechanism of the inhibitory effect of atorvastatin on endoglin expression induced by transforming growth factor-beta1 in cultured cardiac fibroblasts.

Authors: Shyu, KG  Wang, BW  Chen, WJ  Kuan, P  Hung, CR 
Citation: Shyu KG, etal., Eur J Heart Fail. 2010 Mar;12(3):219-26. doi: 10.1093/eurjhf/hfq011.
RGD ID: 7257540
Pubmed: PMID:20156938   (View Abstract at PubMed)
DOI: DOI:10.1093/eurjhf/hfq011   (Journal Full-text)

AIMS: Transforming growth factor-beta1 (TGF-beta1) and endoglin play a causal role in promoting cardiac fibrosis. Atorvastatin has been shown to have an inhibitory effect on cardiac fibroblasts in vitro. However, the effects of statins on TGF-beta1 and endoglin are poorly understood. We therefore sought to investigate the molecular mechanisms of atorvastatin on endoglin expression after TGF-beta1 stimulation in cardiac fibroblasts. METHODS AND RESULTS: Cultured cardiac fibroblasts were obtained from adult male Sprague-Dawley rat hearts. TGF-beta1 stimulation increased endoglin and collagen I expression and atorvastatin inhibited the induction of endoglin and collagen I by TGF-beta1. Phosphatidylinositol-3 kinase (PI-3) and Akt inhibitors (wortmannin and Akt inhibitor X) completely attenuated the endoglin protein expression induced by TGF-beta1. TGF-beta1 induced phosphorylation of PI-3 kinase and Akt, while atorvastatin and wortmannin and Akt inhibitor X inhibited the phosphorylation of PI-3 kinase and Akt induced by TGF-beta1. The gel shift and promoter activity assay showed that TGF-beta1 increased Smad3/4-binding activity and endoglin promoter activity, while wortmannin and atorvastatin inhibited the Smad3/4-binding activity and endoglin promoter activity induced by TGF-beta1. TGF-beta1 increased collagen I protein expression, while endoglin siRNA attenuated collagen I protein expression induced by TGF-beta1. Atorvastatin decreased left ventricular TGF-beta1, endoglin, and collagen I protein expression and fibrotic area in a rat model of volume overload heart failure. CONCLUSION: Atorvastatin inhibits endoglin expression through the inhibition of PI-3 kinase, Akt, and Smad3 phosphorylation, and reduced Smad3/4 binding activity and endoglin promoter activity in cardiac fibroblasts.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
congestive heart failure treatmentISOEng (Rattus norvegicus)7257540; 7257540 RGD 
congestive heart failure  ISOEng (Rattus norvegicus)7257540; 7257540protein:increased expression:heart left ventricle (rat)RGD 
congestive heart failure treatmentIDA 7257540 RGD 
congestive heart failure  IEP 7257540protein:increased expression:heart left ventricle (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of collagen biosynthetic process  IMP 7257540 RGD 
response to xenobiotic stimulus  IEP 7257540atorvastatinRGD 

Objects Annotated

Genes (Rattus norvegicus)
Eng  (endoglin)

Genes (Mus musculus)
Eng  (endoglin)

Genes (Homo sapiens)
ENG  (endoglin)


Additional Information