RGD Reference Report - Heart failure and angiotensin II modulate atrial Pitx2c promotor methylation. - Rat Genome Database

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Heart failure and angiotensin II modulate atrial Pitx2c promotor methylation.

Authors: Kao, YH  Chen, YC  Chung, CC  Lien, GS  Chen, SA  Kuo, CC  Chen, YJ 
Citation: Kao YH, etal., Clin Exp Pharmacol Physiol. 2013 Jun;40(6):379-84. doi: 10.1111/1440-1681.12089.
RGD ID: 9588286
Pubmed: PMID:23573917   (View Abstract at PubMed)
DOI: DOI:10.1111/1440-1681.12089   (Journal Full-text)

Heart failure (HF) can increase atrial fibrillation and induce cardiac hypermethylation. The homeobox gene Pitx2c plays important roles in the genesis of atrial fibrillation and the promoter region of Pitx2c contains cytosine-phosphate-guanine islands. Therefore, epigenetic modification by hypermethylation may reduce Pitx2c expression in atrial myocytes. The aim of the present study were to evaluate whether HF can modulate DNA methylation of Pitx2c and the potential mechanisms involved. We used real-time polymerase chain reaction, immunoblotting and pyrosequencing to investigate RNA and protein expression, as well as the methylation of Pitx2c, in isoproterenol-induced HF, healthy rat left atria and in HL-1 cells with and without (control) exposure to angiotensin (Ang) II (0.1 and 1 mumol/L) or isoproterenol (1 or 10 mumol/L) for 24 h. The HF atrium exhibited increased Pitx2c promoter methylation with increased DNA methyltransferase (DNMT) 1 and decreased Pitx2c protein levels compared with the normal atrium. Angiotensin II (0.1 and 1 mumol/L), increased Pitx2c promoter methylation in HL-1 cells with increased DNMT1 and decreased Pitx2c and Kir2.1 protein levels compared with control cells. These effects were attenuated by the methylation inhibitor 5-aza-2'-deoxycytidine (0.1 mumol/L) and by the AngII receptor blocker losartan (10 mumol/L). However, isoproterenol (1 and 10 mumol/L) did not change the expression of the Pitx2c, DNMT1 and Kir2.1 proteins. In conclusion, HF induces Pitx2c promoter hypermethylation and AngII may contribute to the hypermethylation in HF.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
congestive heart failure  ISODnmt1 (Rattus norvegicus)9588286; 9588286protein:increased expression:atrium:RGD 
congestive heart failure  IEP 9588286protein:increased expression:atrium:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dnmt1  (DNA methyltransferase 1)

Genes (Mus musculus)
Dnmt1  (DNA methyltransferase 1)

Genes (Homo sapiens)
DNMT1  (DNA methyltransferase 1)


Additional Information