Unique transcriptional profile of sustained ligand-activated preconditioning in pre- and post-ischemic myocardium.

<h4>Background</h4>Opioidergic SLP (sustained ligand-activated preconditioning) induced by 3-5 days of opioid receptor (OR) agonism induces persistent protection against ischemia-reperfusion (I-R) injury in young and aged hearts, and is mechanistically distinct from conventional precondi...

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Autores principales:	Kevin J Ashton, Amanda Tupicoff, Grant Williams-Pritchard, Can J Kiessling, Louise E See Hoe, John P Headrick, Jason N Peart
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6f05704634eb4f2c89a187de9c1c4886
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spelling	oai:doaj.org-article:6f05704634eb4f2c89a187de9c1c48862021-11-18T08:58:33ZUnique transcriptional profile of sustained ligand-activated preconditioning in pre- and post-ischemic myocardium.1932-620310.1371/journal.pone.0072278https://doaj.org/article/6f05704634eb4f2c89a187de9c1c48862013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23991079/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Opioidergic SLP (sustained ligand-activated preconditioning) induced by 3-5 days of opioid receptor (OR) agonism induces persistent protection against ischemia-reperfusion (I-R) injury in young and aged hearts, and is mechanistically distinct from conventional preconditioning responses. We thus applied unbiased gene-array interrogation to identify molecular effects of SLP in pre- and post-ischemic myocardium.<h4>Methodology/principal findings</h4>Male C57Bl/6 mice were implanted with 75 mg morphine or placebo pellets for 5 days. Resultant SLP did not modify cardiac function, and markedly reduced dysfunction and injury in perfused hearts subjected to 25 min ischemia/45 min reperfusion. Microarray analysis identified 14 up- and 86 down-regulated genes in normoxic hearts from SLP mice (≥1.3-fold change, FDR≤5%). Induced genes encoded sarcomeric/contractile proteins (Myh7, Mybpc3,Myom2,Des), natriuretic peptides (Nppa,Nppb) and stress-signaling elements (Csda,Ptgds). Highly repressed genes primarily encoded chemokines (Ccl2,Ccl4,Ccl7,Ccl9,Ccl13,Ccl3l3,Cxcl3), cytokines (Il1b,Il6,Tnf) and other proteins involved in inflammation/immunity (C3,Cd74,Cd83, Cd86,Hla-dbq1,Hla-drb1,Saa1,Selp,Serpina3), together with endoplasmic stress proteins (known: Dnajb1,Herpud1,Socs3; putative: Il6, Gadd45g,Rcan1) and transcriptional controllers (Egr2,Egr3, Fos,Hmox1,Nfkbid). Biological themes modified thus related to inflammation/immunity, together with cellular/cardiovascular movement and development. SLP also modified the transcriptional response to I-R (46 genes uniquely altered post-ischemia), which may influence later infarction/remodeling. This included up-regulated determinants of cellular resistance to oxidant (Mgst3,Gstm1,Gstm2) and other forms of stress (Xirp1,Ankrd1,Clu), and repression of stress-response genes (Hspa1a,Hspd1,Hsp90aa,Hsph1,Serpinh1) and Txnip.<h4>Conclusions</h4>Protection via SLP is associated with transcriptional repression of inflammation/immunity, up-regulation of sarcomeric elements and natriuretic peptides, and modulation of cell stress, growth and development, while conventional protective molecules are unaltered.Kevin J AshtonAmanda TupicoffGrant Williams-PritchardCan J KiesslingLouise E See HoeJohn P HeadrickJason N PeartPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e72278 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kevin J Ashton Amanda Tupicoff Grant Williams-Pritchard Can J Kiessling Louise E See Hoe John P Headrick Jason N Peart Unique transcriptional profile of sustained ligand-activated preconditioning in pre- and post-ischemic myocardium.
description	<h4>Background</h4>Opioidergic SLP (sustained ligand-activated preconditioning) induced by 3-5 days of opioid receptor (OR) agonism induces persistent protection against ischemia-reperfusion (I-R) injury in young and aged hearts, and is mechanistically distinct from conventional preconditioning responses. We thus applied unbiased gene-array interrogation to identify molecular effects of SLP in pre- and post-ischemic myocardium.<h4>Methodology/principal findings</h4>Male C57Bl/6 mice were implanted with 75 mg morphine or placebo pellets for 5 days. Resultant SLP did not modify cardiac function, and markedly reduced dysfunction and injury in perfused hearts subjected to 25 min ischemia/45 min reperfusion. Microarray analysis identified 14 up- and 86 down-regulated genes in normoxic hearts from SLP mice (≥1.3-fold change, FDR≤5%). Induced genes encoded sarcomeric/contractile proteins (Myh7, Mybpc3,Myom2,Des), natriuretic peptides (Nppa,Nppb) and stress-signaling elements (Csda,Ptgds). Highly repressed genes primarily encoded chemokines (Ccl2,Ccl4,Ccl7,Ccl9,Ccl13,Ccl3l3,Cxcl3), cytokines (Il1b,Il6,Tnf) and other proteins involved in inflammation/immunity (C3,Cd74,Cd83, Cd86,Hla-dbq1,Hla-drb1,Saa1,Selp,Serpina3), together with endoplasmic stress proteins (known: Dnajb1,Herpud1,Socs3; putative: Il6, Gadd45g,Rcan1) and transcriptional controllers (Egr2,Egr3, Fos,Hmox1,Nfkbid). Biological themes modified thus related to inflammation/immunity, together with cellular/cardiovascular movement and development. SLP also modified the transcriptional response to I-R (46 genes uniquely altered post-ischemia), which may influence later infarction/remodeling. This included up-regulated determinants of cellular resistance to oxidant (Mgst3,Gstm1,Gstm2) and other forms of stress (Xirp1,Ankrd1,Clu), and repression of stress-response genes (Hspa1a,Hspd1,Hsp90aa,Hsph1,Serpinh1) and Txnip.<h4>Conclusions</h4>Protection via SLP is associated with transcriptional repression of inflammation/immunity, up-regulation of sarcomeric elements and natriuretic peptides, and modulation of cell stress, growth and development, while conventional protective molecules are unaltered.
format	article
author	Kevin J Ashton Amanda Tupicoff Grant Williams-Pritchard Can J Kiessling Louise E See Hoe John P Headrick Jason N Peart
author_facet	Kevin J Ashton Amanda Tupicoff Grant Williams-Pritchard Can J Kiessling Louise E See Hoe John P Headrick Jason N Peart
author_sort	Kevin J Ashton
title	Unique transcriptional profile of sustained ligand-activated preconditioning in pre- and post-ischemic myocardium.
title_short	Unique transcriptional profile of sustained ligand-activated preconditioning in pre- and post-ischemic myocardium.
title_full	Unique transcriptional profile of sustained ligand-activated preconditioning in pre- and post-ischemic myocardium.
title_fullStr	Unique transcriptional profile of sustained ligand-activated preconditioning in pre- and post-ischemic myocardium.
title_full_unstemmed	Unique transcriptional profile of sustained ligand-activated preconditioning in pre- and post-ischemic myocardium.
title_sort	unique transcriptional profile of sustained ligand-activated preconditioning in pre- and post-ischemic myocardium.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/6f05704634eb4f2c89a187de9c1c4886
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Unique transcriptional profile of sustained ligand-activated preconditioning in pre- and post-ischemic myocardium.

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