| Effect of pressure overload on cardioprotection via PI3K-Akt: comparison of postconditioning, insulin, and pressure unloading. | |
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MedLine Citation:
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PMID: 20300072 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Postconditioning (PC) and insulin exert cardioprotection by activating phosphatidylinositol-3 kinase (PI3K) signaling. Because pressure overload exacerbates ischemia-reperfusion (IR) injury, we tested the hypothesis that (i) pressure overload attenuates PC- and insulin-induced cardioprotection, an effect caused by reduced PI3K-Akt signaling and (ii) pressure unloading confers cardioprotection comparable to either PC or insulin. METHODS: Infarct size (IS) and levels of relevant proteins (i.e., Akt, glycogen synthase kinase-3beta (GSK-3beta), 3'-phosphoinositide dependent kinase 1 (PDK1), phosphatase and tensin homolog on chromosome ten (PTEN)) were determined in hearts subjected to IR. RESULTS: Pressure overload increased IS in association with changes in protein levels consistent with reduced PI3K-Akt signaling (i.e., ischemic reperfused vs. normoxic hearts). PC and insulin reduced IS but it was greater in hearts perfused at the higher, than the lower, pressure. Wortmannin (PI3K inhibitor) partially reversed PC-induced cardioprotection, with IS being greater in the high-pressure group. Pressure unloading during reperfusion caused the most marked reduction in IS whereas pressure loading abolished PC-induced cardioprotection. Nonetheless, the phospho-Akt/total Akt ratios and phospho-GSK-3beta levels were unaffected by perfusion pressure in insulin-treated or postconditioned hearts. Moreover, protein levels were similar in pressure-unloaded and pressure-loaded hearts. CONCLUSIONS: Pressure overload reduces PI3K-Akt signaling following IR. However, a differential in PI3K-Akt signaling was not observed in ischemia-reperfused, insulin-treated, and postconditioned hearts, suggesting involvement of pathways other than PI3K-Akt for the effect of pressure on IS. Importantly, pressure unloading at reperfusion represents a novel and effective cardioprotective maneuver. |
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Authors:
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Mahmood S Mozaffari; Jun Yao Liu; Stephen W Schaffer |
Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-18 |
Journal Detail:
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Title: American journal of hypertension Volume: 23 ISSN: 1941-7225 ISO Abbreviation: Am. J. Hypertens. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-18 Completed Date: 2010-08-20 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 8803676 Medline TA: Am J Hypertens Country: United States |
Other Details:
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Languages: eng Pagination: 668-74 Citation Subset: IM |
Affiliation:
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Department of Oral Biology, Medical College of Georgia School of Dentistry, Augusta, Georgia, USA. Mmozaffa@mail.mcg.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Androstadienes
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pharmacology Animals Glycogen Synthase Kinase 3 Heart / drug effects Insulin / pharmacology* Male Myocardial Infarction / pathology, prevention & control Myocardial Reperfusion Injury / prevention & control* Myocardium / metabolism* PTEN Phosphohydrolase / metabolism Phosphatidylinositol 3-Kinases / antagonists & inhibitors, metabolism* Pressure* Protein-Serine-Threonine Kinases / metabolism Proto-Oncogene Proteins c-akt / metabolism* Rats Rats, Sprague-Dawley Signal Transduction / physiology* Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Androstadienes; 11061-68-0/Insulin; 19545-26-7/wortmannin; EC 2.7.1.-/3-phosphoinositide-dependent protein kinase; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3; EC 3.1.3.48/Pten protein, rat; EC 3.1.3.67/PTEN Phosphohydrolase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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