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Article: Adrenomedullin is a regulated modulator of neonatal cardiomyocyte hypertrophy in vitro

TitleAdrenomedullin is a regulated modulator of neonatal cardiomyocyte hypertrophy in vitro
Authors
KeywordsAdrenergic (ant)agonists
Endothelins
Gene expression
Hypertrophy
Receptors
Issue Date2001
PublisherOxford University Press. The Journal's web site is located at http://cardiovascres.oxfordjournals.org
Citation
Cardiovascular Research, 2001, v. 51 n. 2, p. 255-264 How to Cite?
AbstractObjective: Adrenomedullin is a potent hypotensive, natriuretic and diuretic peptide that is coexpressed in the heart with its receptor, suggesting that it may have localized actions as a modulator of cardiac function. Although expression of adrenomedullin is upregulated in the pathological heart, its cardiac function has not been clearly elucidated and it is not known whether this represents a common feature of cardiac hypertrophy, nor whether this is restricted to cardiac myocytes. We have determined the direct effects of hypertrophic agents on cardiomyocyte adrenomedullin gene expression and peptide secretion and have examined the effects of adrenomedullin on biochemical markers of cardiomyocyte hypertrophy. Methods: Regulation of adrenomedullin expression and its effects on the hypertrophic response were studied in cultured rat neonatal ventricular cardiomyocytes. Results: Incubation with phenylephrine or endothelin for 48 h led to a hypertrophic response with an associated fivefold stimulation of ANP gene expression. In contrast, adrenomedullin mRNA was inhibited by 30-50% in response to phenylephrine or endothelin-mediated hypertrophy, and this was associated with a 35-45% reduction in secretion of immunoreactive adrenomedullin. Phorbol ester mediated activation of protein kinase C and increasing intracellular Ca2+ with ionomycin led to significant downregulation of adrenomedullin gene expression in cardiomyocytes. Co-incubation with 100 nM adrenomedullin for 48 h inhibited phenylephrine-induced cardiomyocyte hypertrophy as determined by protein:DNA ratio. Adrenomedullin partially blocked phenylephrine-mediated transcriptional activation of ANP and MLC-2 reporter gene expression in cardiomyocytes and this effect was mimicked by 2 μM forskolin, suggesting that this response was mediated via the activation of adenylate cyclase. Conclusion: These data demonstrate that the cardiomyocyte adrenomedullin gene is repressed by phenylephrine or endothelin-mediated hypertrophy. The inhibitory effects of adrenomedullin on the cardiomyocyte hypertrophic response suggests that this peptide acts as a regulated autocrine or paracrine modulator of cardiomyocyte function and that downregulation of adrenomedullin expression may play a role in induction and maintenance of cardiomyocyte hypertrophy. © 2001 Elsevier Science B.V. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/81185
ISSN
2015 Impact Factor: 5.465
2015 SCImago Journal Rankings: 2.897
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorAutelitano, DJen_HK
dc.contributor.authorRidings, Ren_HK
dc.contributor.authorTang, Fen_HK
dc.date.accessioned2010-09-06T08:14:48Z-
dc.date.available2010-09-06T08:14:48Z-
dc.date.issued2001en_HK
dc.identifier.citationCardiovascular Research, 2001, v. 51 n. 2, p. 255-264en_HK
dc.identifier.issn0008-6363en_HK
dc.identifier.urihttp://hdl.handle.net/10722/81185-
dc.description.abstractObjective: Adrenomedullin is a potent hypotensive, natriuretic and diuretic peptide that is coexpressed in the heart with its receptor, suggesting that it may have localized actions as a modulator of cardiac function. Although expression of adrenomedullin is upregulated in the pathological heart, its cardiac function has not been clearly elucidated and it is not known whether this represents a common feature of cardiac hypertrophy, nor whether this is restricted to cardiac myocytes. We have determined the direct effects of hypertrophic agents on cardiomyocyte adrenomedullin gene expression and peptide secretion and have examined the effects of adrenomedullin on biochemical markers of cardiomyocyte hypertrophy. Methods: Regulation of adrenomedullin expression and its effects on the hypertrophic response were studied in cultured rat neonatal ventricular cardiomyocytes. Results: Incubation with phenylephrine or endothelin for 48 h led to a hypertrophic response with an associated fivefold stimulation of ANP gene expression. In contrast, adrenomedullin mRNA was inhibited by 30-50% in response to phenylephrine or endothelin-mediated hypertrophy, and this was associated with a 35-45% reduction in secretion of immunoreactive adrenomedullin. Phorbol ester mediated activation of protein kinase C and increasing intracellular Ca2+ with ionomycin led to significant downregulation of adrenomedullin gene expression in cardiomyocytes. Co-incubation with 100 nM adrenomedullin for 48 h inhibited phenylephrine-induced cardiomyocyte hypertrophy as determined by protein:DNA ratio. Adrenomedullin partially blocked phenylephrine-mediated transcriptional activation of ANP and MLC-2 reporter gene expression in cardiomyocytes and this effect was mimicked by 2 μM forskolin, suggesting that this response was mediated via the activation of adenylate cyclase. Conclusion: These data demonstrate that the cardiomyocyte adrenomedullin gene is repressed by phenylephrine or endothelin-mediated hypertrophy. The inhibitory effects of adrenomedullin on the cardiomyocyte hypertrophic response suggests that this peptide acts as a regulated autocrine or paracrine modulator of cardiomyocyte function and that downregulation of adrenomedullin expression may play a role in induction and maintenance of cardiomyocyte hypertrophy. © 2001 Elsevier Science B.V. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://cardiovascres.oxfordjournals.orgen_HK
dc.relation.ispartofCardiovascular Researchen_HK
dc.rightsCardiovascular Research. Copyright © Elsevier BV.en_HK
dc.subjectAdrenergic (ant)agonistsen_HK
dc.subjectEndothelinsen_HK
dc.subjectGene expressionen_HK
dc.subjectHypertrophyen_HK
dc.subjectReceptorsen_HK
dc.titleAdrenomedullin is a regulated modulator of neonatal cardiomyocyte hypertrophy in vitroen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-6363&volume=51&spage=255&epage=264&date=2001&atitle=Adrenomedullin+is+a+regulated+modulator+of+neonatal+cardiomyocyte+hypertrophy+in+vitroen_HK
dc.identifier.emailTang, F: ftang@hkucc.hku.hken_HK
dc.identifier.authorityTang, F=rp00327en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/S0008-6363(01)00318-2en_HK
dc.identifier.pmid11470465-
dc.identifier.scopuseid_2-s2.0-0034940394en_HK
dc.identifier.hkuros63731en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034940394&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume51en_HK
dc.identifier.issue2en_HK
dc.identifier.spage255en_HK
dc.identifier.epage264en_HK
dc.identifier.isiWOS:000170497800010-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridAutelitano, DJ=7003803451en_HK
dc.identifier.scopusauthoridRidings, R=6602533533en_HK
dc.identifier.scopusauthoridTang, F=7201979770en_HK

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