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• W1992591882 startingPage "508" @default.
• W1992591882 abstract "The purpose of this study was to determine whether atorvastatin, a 3-hydroxy-3-methylglutaryl (HMG)-co-enzyme A (CoA) reductase inhibitor, limits myocardial necrosis when administered as an adjunct to reperfusion.Statins inhibit HMG-CoA reductase to reduce the synthesis of cholesterol. However, it is proposed that statins have cardiovascular effects beyond their ability to lower cholesterol, possibly via recruitment of phosphatidyl inositol 3-kinase (PI3K) and the serine/threonine kinase, Akt. This signaling pathway has recently been linked to growth factor-mediated reperfusion salvage.Isolated perfused mouse hearts were subjected to 35 min of global ischemia and reperfused for 30 min in the presence of incremental concentrations of atorvastatin. Infarct size was determined by triphenyltetrazolium chloride staining, and the activity of the PI3K signaling cascade was determined by Western blot analysis.We found that there was a profound dose-dependent reduction of infarct size with atorvastatin in the range of 25 to 100 micromol/l (optimal protection was seen at 50 micromol/l with infarct size of 16 +/- 2% vs. control, 33 +/- 2%, p < 0.01). Moreover, this protection was sensitive to inhibition with the PI3 kinase inhibitor, wortmannin, and was absent in endothelial nitric oxide synthase (eNOS) knockout mice. Western blot analysis revealed that atorvastatin resulted in rapid activation of the PI3K/Akt signaling cascade (within 5 min) and that both Akt and eNOS phosphorylation were significantly increased by 4.1-fold and 2.9-fold, respectively (p < 0.01). Moreover, phosphorylation of the PI3K substrates was abrogated by the administration of wortmannin.Atorvastatin attenuates lethal reperfusion-induced injury in a manner that is reliant on PI3K and Akt activity and the presence and activity of eNOS." @default.
• W1992591882 created "2016-06-24" @default.
• W1992591882 creator A5031110077 @default.
• W1992591882 creator A5090808868 @default.
• W1992591882 date "2003-02-01" @default.
• W1992591882 modified "2023-10-14" @default.
• W1992591882 title "Atorvastatin, administered at the onset of reperfusion, and independent oflipid lowering, protects the myocardiumby up-regulating a pro-survival pathway" @default.
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• W1992591882 doi "https://doi.org/10.1016/s0735-1097(02)02816-4" @default.
• W1992591882 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12575984" @default.
• W1992591882 hasPublicationYear "2003" @default.
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