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dc.contributor.authorDobson, James G. Jr.
dc.contributor.authorFray, John
dc.contributor.authorLeonard, Jack L.
dc.contributor.authorPratt, Richard E.
dc.date2022-08-11T08:10:16.000
dc.date.accessioned2022-08-23T17:02:03Z
dc.date.available2022-08-23T17:02:03Z
dc.date.issued2003-10-17
dc.date.submitted2008-06-09
dc.identifier.citationPhysiol Genomics. 2003 Oct 17;15(2):142-7. <a href="http://dx.doi.org/10.1152/physiolgenomics.00076.2003">Link to article on publisher's site</a>
dc.identifier.issn1531-2267 (Electronic)
dc.identifier.doi10.1152/physiolgenomics.00076.2003
dc.identifier.pmid12902548
dc.identifier.urihttp://hdl.handle.net/20.500.14038/44138
dc.description.abstractMyocardial aging leads to a reduction of beta-adrenergic receptor-induced metabolic and contractile responsiveness. We hypothesize that a change in the patterns of gene expression is important in these age-related events. To test this, hearts were harvested from young and aged male rats (3-4 and 20-22 mo, respectively). Total mRNA was extracted and prepared for hybridization to Affymetrix U34A GeneChips. Filtering criteria, involving fold change and a statistical significance cutoff were employed, yielding 263 probe pairs exhibiting differential signals. Of the 163 annotated genes, at least 56 (34%) were classified as signaling/cell communication. Of these 56, approximately half were directly involved in G protein-coupled receptor signaling pathways. We next determined which of these changes might be involved in anti-adrenergic activity and identified 19 potentially important gene products. Importantly, we observed a decrease in beta1-adrenergic receptor and adenylyl cyclase mRNAs, whereas the mRNA encoding beta-arrestin increased. Furthermore, the results demonstrate an increase in mRNAs encoding the adenosine A1 receptor and phospholipase D, which could increase anti-adrenergic effects. Moreover, the mRNAs encoding the muscarinic M3 receptor, nicotinic acetylcholine receptor beta3, and nicotinic acetylcholine receptor-related protein were increased as was the mRNA encoding guanylate kinase-associated protein. Interestingly, we also observed eight mRNAs whose abundance changed three- to sixfold with aging that could be considered as being compensatory. Although these results do not prove causality, they demonstrate that cardiac aging is associated with changes in the profiles of gene expression and that many of these changes may contribute to reduced adrenergic signaling.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12902548&dopt=Abstract ">Link to article in PubMed</a>
dc.relation.urlhttp://physiolgenomics.physiology.org/content/15/2/142.full.pdf+html
dc.subjectAdenylate Cyclase
dc.subjectAging
dc.subjectAnimals
dc.subjectGene Expression Profiling
dc.subjectHeart
dc.subjectMale
dc.subjectMyocardium
dc.subjectOligonucleotide Array Sequence Analysis
dc.subjectProtein Biosynthesis
dc.subjectProteins
dc.subjectRNA, Messenger
dc.subjectRats
dc.subjectRats, Inbred F344
dc.subjectReceptors, Adrenergic, beta
dc.subject*Signal Transduction
dc.subjectCardiovascular Diseases
dc.subjectGenetics and Genomics
dc.subjectMolecular Genetics
dc.subjectPhysiology
dc.titleMolecular mechanisms of reduced beta-adrenergic signaling in the aged heart as revealed by genomic profiling
dc.typeJournal Article
dc.source.journaltitlePhysiological genomics
dc.source.volume15
dc.source.issue2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/physio_pp/20
dc.identifier.contextkey521872
html.description.abstract<p>Myocardial aging leads to a reduction of beta-adrenergic receptor-induced metabolic and contractile responsiveness. We hypothesize that a change in the patterns of gene expression is important in these age-related events. To test this, hearts were harvested from young and aged male rats (3-4 and 20-22 mo, respectively). Total mRNA was extracted and prepared for hybridization to Affymetrix U34A GeneChips. Filtering criteria, involving fold change and a statistical significance cutoff were employed, yielding 263 probe pairs exhibiting differential signals. Of the 163 annotated genes, at least 56 (34%) were classified as signaling/cell communication. Of these 56, approximately half were directly involved in G protein-coupled receptor signaling pathways. We next determined which of these changes might be involved in anti-adrenergic activity and identified 19 potentially important gene products. Importantly, we observed a decrease in beta1-adrenergic receptor and adenylyl cyclase mRNAs, whereas the mRNA encoding beta-arrestin increased. Furthermore, the results demonstrate an increase in mRNAs encoding the adenosine A1 receptor and phospholipase D, which could increase anti-adrenergic effects. Moreover, the mRNAs encoding the muscarinic M3 receptor, nicotinic acetylcholine receptor beta3, and nicotinic acetylcholine receptor-related protein were increased as was the mRNA encoding guanylate kinase-associated protein. Interestingly, we also observed eight mRNAs whose abundance changed three- to sixfold with aging that could be considered as being compensatory. Although these results do not prove causality, they demonstrate that cardiac aging is associated with changes in the profiles of gene expression and that many of these changes may contribute to reduced adrenergic signaling.</p>
dc.identifier.submissionpathphysio_pp/20
dc.contributor.departmentDepartment of Physiology
dc.source.pages142-7


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