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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2004-10-11
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pubmed:abstractText |
Long-term pretreatment with statins reduces myocardial injury after acute ischemia and reperfusion by increasing the expression of endothelial nitric oxide synthase (eNOS). We hypothesized that statins may act rapidly enough to protect the myocardium from ischemia/reperfusion injury when given right at the beginning of the reperfusion period and tried to delineate the role of PI 3-kinase/Akt pathway in early eNOS activation. Activated simvastatin was given intravenously 3 minutes before starting the reperfusion after temporary coronary artery occlusion (CAO) in anaesthetized rats. Simvastatin significantly increased myocardial PI 3-kinase activity, AktSer473, and eNOSSer1177 phosphorylation and reduced infarct size by 42%. Infarct size reduction as well as activation of PI 3-kinase/Akt/eNOS pathway were not observed in rats co-treated with the PI 3-kinase inhibitor wortmannin. Contribution of eNOS was further delineated using the NOS inhibitor L-NAME, which could completely block cardioprotection by the statin. In summary, simvastatin acutely reduces the extent of myocardial necrosis in normocholesterolemic rats in an NO- dependent manner by activating the PI 3-kinase/Akt pathway. This is the first study demonstrating short-term cardioprotective effects of simvastatin in an in vivo model of ischemia/reperfusion.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Akt1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Androstadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/NG-Nitroarginine Methyl Ester,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type III,
http://linkedlifedata.com/resource/pubmed/chemical/Nos3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Simvastatin,
http://linkedlifedata.com/resource/pubmed/chemical/wortmannin
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0160-2446
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
348-55
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15475833-Androstadienes,
pubmed-meshheading:15475833-Animals,
pubmed-meshheading:15475833-Cholesterol,
pubmed-meshheading:15475833-Coronary Stenosis,
pubmed-meshheading:15475833-Drug Administration Schedule,
pubmed-meshheading:15475833-Injections, Intravenous,
pubmed-meshheading:15475833-Male,
pubmed-meshheading:15475833-Myocardial Infarction,
pubmed-meshheading:15475833-Myocardial Reperfusion Injury,
pubmed-meshheading:15475833-NG-Nitroarginine Methyl Ester,
pubmed-meshheading:15475833-Nitric Oxide Synthase,
pubmed-meshheading:15475833-Nitric Oxide Synthase Type III,
pubmed-meshheading:15475833-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15475833-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15475833-Proto-Oncogene Proteins,
pubmed-meshheading:15475833-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15475833-Rats,
pubmed-meshheading:15475833-Rats, Wistar,
pubmed-meshheading:15475833-Signal Transduction,
pubmed-meshheading:15475833-Simvastatin,
pubmed-meshheading:15475833-Time Factors
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pubmed:year |
2004
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pubmed:articleTitle |
Simvastatin acutely reduces myocardial reperfusion injury in vivo by activating the phosphatidylinositide 3-kinase/Akt pathway.
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pubmed:affiliation |
Medical Clinic II, University of Schleswig-Holstein, Campus Lübeck, Germany. wolfrum@medinf.mu-luebeck.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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