RGD Reference Report - Mechanisms of Ghrelin anti-heart failure: inhibition of Ang II-induced cardiomyocyte apoptosis by down-regulating AT1R expression. - Rat Genome Database

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Mechanisms of Ghrelin anti-heart failure: inhibition of Ang II-induced cardiomyocyte apoptosis by down-regulating AT1R expression.

Authors: Yang, C  Liu, Z  Liu, K  Yang, P 
Citation: Yang C, etal., PLoS One. 2014 Jan 21;9(1):e85785. doi: 10.1371/journal.pone.0085785. eCollection 2014.
RGD ID: 11039412
Pubmed: PMID:24465706   (View Abstract at PubMed)
PMCID: PMC3897516   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0085785   (Journal Full-text)

BACKGROUND: Ghrelin is a novel growth hormone-releasing peptide administered to treat chronic heart failure (CHF). However, the underlying mechanism of its protective effects against heart failure (HF) remains unclear. METHODS AND RESULTS: A total of 68 patients with CHF and 20 healthy individuals were included. The serum levels of Angiotensin II (Ang II) and ghrelin were measured using ELISA. The results showed that Ang II and ghrelin were both significantly increased in CHF patients and that the ghrelin levels were significantly positively correlated with Ang II. The left anterior descending coronary artery was ligated to establish a rat model of CHF, and cultured cardiomyocytes from neonatal rats were stimulated with Ang II to explore the role of ghrelin in CHF. The results showed that ghrelin inhibited cardiomyocyte apoptosis both in vivo and in vitro. Furthermore, caspase-3 expression was examined, and the results revealed that Ang II induces cardiomyocyte apoptosis through the caspase-3 pathway, whereas ghrelin inhibits this action. Lastly, to further elucidate the mechanism by which ghrelin inhibits Ang II action, the expression of the AT1 and AT2 receptors was evaluated; the results showed that Ang II up-regulates the AT1 and AT2 receptors in cardiomyocytes, whereas ghrelin inhibits AT1 receptor up-regulation but does not affect AT2 receptor expression. CONCLUSIONS: These data suggest that the serum levels of ghrelin are significantly positively correlated with Ang II in CHF patients and that ghrelin can inhibit Ang II-induced cardiomyocyte apoptosis by down-regulating AT1R, thereby playing a role in preventing HF.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
congestive heart failure severityIEP 11039412protein:increased expression:serumRGD 
congestive heart failure severityISOAGT (Homo sapiens)11039412; 11039412protein:increased expression:serumRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cardiac muscle cell apoptotic process  IDA 11039412 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Agt  (angiotensinogen)

Genes (Mus musculus)
Agt  (angiotensinogen)

Genes (Homo sapiens)
AGT  (angiotensinogen)


Additional Information