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Conference Paper: The molecular biology of heart failure

TitleThe molecular biology of heart failure
Authors
Issue Date1993
Citation
Journal of the American College of Cardiology, 1993, v. 22 n. 4 suppl. A, p. 30A-33A How to Cite?
AbstractIn the mammalian heart, the development of cardiac hypertrophy is a common feature that normally precedes all forms of heart failure. This adaptive process involves molecular changes in the myocardium, including the altered expressionn of several genes encoding proteins for contraction and relaxation. The expression of myosin heavy chain (MHC) and sarcomeric alpha-actin messenger ribonucleic acid (mRNA) changes qualitatively during cardiac hypertrophy; however, their accumulations are not coordinated. Skeletal alpha-actin transcripts accumulate throughout the ventricles and earlier than beta-MHC transcripts, which accumulate primarily around large coronary vessels. Skeletal alpha-actin transcripts also 'hyperaccumulate' relative to cardiac alpha-actin mRNA, whose expression does not change. Expression of MHC isomRNA shows an inverse relation; as β-MHC accumulates, α-MHC decreases in abundance. From nuclear run-on assays, we present evidence that the accumulation of these gene products is at least under partial transcriptional control with developmental growth, suggesting that those changes that occur with hypertrophy and heart failure may be primarily transcriptionally regulated. The expression of the mRNA for the calcium-adenosine triphosphate (Ca2+-ATPase) of the sarcoplasmic reticulum changes quantitatively with cardiac hypertrophy without the reexpression of a different isoform. The relative mRNA and protein concentrations for this protein diminish with both cardiac hypertrophy and heart failure, a change that may partially explainn the delayed relaxation rates seen in hypertrophied and failing hearts. Preliminary studies suggest that the transcriptional activity of this gene and that for phospholamban, a regulatory protein for the sarcoplasmic reticulum Ca2+-ATPase, can be assayed using the nuclear run-on assays. These studies will enable a more complete understanding of the processes that lead to quantitative and qualitative changes in gene expression with hypertrophy and failure and should in the future lead to the identification of genetic targets for new drugs.
Persistent Identifierhttp://hdl.handle.net/10722/195233
ISSN
2015 Impact Factor: 17.759
2015 SCImago Journal Rankings: 10.097
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSchwartz, K-
dc.contributor.authorChassagne, C-
dc.contributor.authorBoheler, KR-
dc.date.accessioned2014-02-25T01:40:20Z-
dc.date.available2014-02-25T01:40:20Z-
dc.date.issued1993-
dc.identifier.citationJournal of the American College of Cardiology, 1993, v. 22 n. 4 suppl. A, p. 30A-33A-
dc.identifier.issn0735-1097-
dc.identifier.urihttp://hdl.handle.net/10722/195233-
dc.description.abstractIn the mammalian heart, the development of cardiac hypertrophy is a common feature that normally precedes all forms of heart failure. This adaptive process involves molecular changes in the myocardium, including the altered expressionn of several genes encoding proteins for contraction and relaxation. The expression of myosin heavy chain (MHC) and sarcomeric alpha-actin messenger ribonucleic acid (mRNA) changes qualitatively during cardiac hypertrophy; however, their accumulations are not coordinated. Skeletal alpha-actin transcripts accumulate throughout the ventricles and earlier than beta-MHC transcripts, which accumulate primarily around large coronary vessels. Skeletal alpha-actin transcripts also 'hyperaccumulate' relative to cardiac alpha-actin mRNA, whose expression does not change. Expression of MHC isomRNA shows an inverse relation; as β-MHC accumulates, α-MHC decreases in abundance. From nuclear run-on assays, we present evidence that the accumulation of these gene products is at least under partial transcriptional control with developmental growth, suggesting that those changes that occur with hypertrophy and heart failure may be primarily transcriptionally regulated. The expression of the mRNA for the calcium-adenosine triphosphate (Ca2+-ATPase) of the sarcoplasmic reticulum changes quantitatively with cardiac hypertrophy without the reexpression of a different isoform. The relative mRNA and protein concentrations for this protein diminish with both cardiac hypertrophy and heart failure, a change that may partially explainn the delayed relaxation rates seen in hypertrophied and failing hearts. Preliminary studies suggest that the transcriptional activity of this gene and that for phospholamban, a regulatory protein for the sarcoplasmic reticulum Ca2+-ATPase, can be assayed using the nuclear run-on assays. These studies will enable a more complete understanding of the processes that lead to quantitative and qualitative changes in gene expression with hypertrophy and failure and should in the future lead to the identification of genetic targets for new drugs.-
dc.languageeng-
dc.relation.ispartofJournal of the American College of Cardiology-
dc.titleThe molecular biology of heart failure-
dc.typeConference_Paper-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/0735-1097(93)90459-E-
dc.identifier.pmid8376695-
dc.identifier.scopuseid_2-s2.0-0027360568-
dc.identifier.volume22-
dc.identifier.issue4 suppl. A-
dc.identifier.spage30A-
dc.identifier.epage33A-
dc.identifier.isiWOS:A1993MR86900006-
dc.customcontrol.immutablesml 160520 amended-

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