| Cardiac-generated prostanoids mediate cardiac myocyte apoptosis after myocardial ischaemia. | |
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MedLine Citation:
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PMID: 22707158 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: The objective of the present study is to elucidate the pathogenic role of eicosanoids in myocardial infarction (MI). The accumulation of eicosanoid metabolites in ischaemic myocardium has been demonstrated in animal models and patients with MI, and it occurs in parallel with the development of irreversible cardiac damage. However, the key question that remains unanswered is whether cardiac-generated eicosanoids are the cause or the consequence of cardiac cell damage in MI. METHODS AND RESULTS: We used a clinically relevant animal model of MI and metabolic profiling to monitor the eicosanoid profile in ischaemic myocardium. We demonstrate that ischaemia induces the generation of prostanoids mainly through the cyclooxygenase (COX)-1 pathway in the myocardium. Cardiac-generated prostanoids, particularly prostaglandin D(2) (PGD(2)), can directly induce apoptosis in cardiac myocytes. This effect involves the up-regulation of the pro-apoptotic gene, Fas ligand (FasL), in a D-type prostanoid receptor-independent manner. The treatment of the MI mice with low-dose aspirin effectively inhibits the ischaemia-induced prostanoid generation and FasL expression in the myocardium, leading to the reduction in cardiac apoptosis following cardiac ischaemia. CONCLUSIONS: Cardiac ischaemia results in COX-1-mediated generation of prostanoids, which by inducing cardiac myocyte apoptosis, contribute to the cardiac cell loss following MI. The benefits of low-dose aspirin treatment in MI may be attributable, in part, to the inhibition of cardiac prostanoid generation and attenuation of apoptosis. Further understanding of the mechanisms underlying prostanoid-induced cardiac apoptosis may be of significant value in designing new therapeutic strategies to prevent aberrant cell loss following MI and subsequent progression to heart failure. |
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Authors:
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Hong Qiu; Jun-Yan Liu; Dongguang Wei; Ning Li; Ebenezer N Yamoah; Bruce D Hammock; Nipavan Chiamvimonvat |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2012-06-15 |
Journal Detail:
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Title: Cardiovascular research Volume: 95 ISSN: 1755-3245 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-07-20 Completed Date: 2012-12-04 Revised Date: 2013-06-03 |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: England |
Other Details:
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Languages: eng Pagination: 336-45 Citation Subset: IM |
Affiliation:
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Division of Cardiovascular Medicine, Department of Internal Medicine, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Apoptosis* / drug effects, genetics Aspirin / pharmacology Cells, Cultured Cyclooxygenase 1 / metabolism Cyclooxygenase Inhibitors / pharmacology Disease Models, Animal Fas Ligand Protein / genetics, metabolism Male Membrane Proteins / metabolism Mice Mice, Inbred C57BL Myocardial Ischemia / genetics, metabolism*, pathology, physiopathology Myocardium / metabolism*, pathology Prostaglandin D2 / metabolism Prostaglandins / blood, metabolism* RNA, Messenger / metabolism Receptors, Immunologic / metabolism Receptors, Prostaglandin / metabolism Time Factors Up-Regulation Ventricular Function, Left |
| Grant Support | |
ID/Acronym/Agency:
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DC010917/DC/NIDCD NIH HHS; ES02710/ES/NIEHS NIH HHS; ES04699/ES/NIEHS NIH HHS; HL85727/HL/NHLBI NIH HHS; HL85844/HL/NHLBI NIH HHS; I01 BX000576/BX/BLRD VA; P42 ES004699/ES/NIEHS NIH HHS; R01 ES002710/ES/NIEHS NIH HHS; R01 HL085727/HL/NHLBI NIH HHS; R01 HL085844/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclooxygenase Inhibitors; 0/Fas Ligand Protein; 0/Fasl protein, mouse; 0/Membrane Proteins; 0/Prostaglandins; 0/RNA, Messenger; 0/Receptors, Immunologic; 0/Receptors, Prostaglandin; 0/prostaglandin D2 receptor; 41598-07-6/Prostaglandin D2; 50-78-2/Aspirin; EC 1.14.99.1/Cyclooxygenase 1; EC 1.14.99.1/Ptgs1 protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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