@article{3125526,
    title = "Transient carotid ischemia as a remote conditioning stimulus for myocardial protection in anesthetized rabbits: Insights into intracellular signaling",
    author = "Andreadou, I. and Bibli, S.-I. and Mastromanolis, E. and Zoga, A. and Efentakis, P. and Papaioannou, N. and Farmakis, D. and Kremastinos, D.Th. and Iliodromitis, E.K.",
    journal = "International Journal of Cardiology",
    year = "2015",
    volume = "184",
    number = "1",
    pages = "140-151",
    publisher = "Elsevier Ireland Ltd",
    issn = "0167-5273",
    doi = "10.1016/j.ijcard.2015.01.079",
    keywords = "4 amino 7 tert butyl 5 (4 methylphenyl)pyrazolo[3,4 d]pyrimidine;  angiotensin II;  caspase 3;  endothelial nitric oxide synthase;  glycogen synthase kinase 3beta;  Janus kinase 2;  mitogen activated protein kinase 1;  mitogen activated protein kinase 3;  n benzyl 2 cyano 3 (3,4 dihydroxyphenyl)acrylamide;  n(g) nitroarginine methyl ester;  phosphatidylinositol 3 kinase;  protein kinase B;  protein tyrosine kinase;  STAT3 protein;  STAT5 protein;  valsartan;  wortmannin, animal experiment;  animal model;  animal tissue;  Article;  carotid artery;  controlled study;  heart infarction;  heart infarction prevention;  heart infarction size;  heart protection;  intracellular signaling;  ischemia;  male;  nonhuman;  perconditioning;  priority journal;  protein expression;  protein phosphorylation;  reperfusion;  animal;  carotid artery;  heart infarction prevention;  intracellular fluid;  metabolism;  Myocardial Infarction;  Myocardial Ischemia;  pathology;  physiology;  procedures;  rabbit;  signal transduction, Animals;  Carotid Arteries;  Intracellular Fluid;  Ischemic Preconditioning, Myocardial;  Male;  Myocardial Infarction;  Myocardial Ischemia;  Rabbits;  Signal Transduction",
    abstract = "Background: We investigated the effectiveneß of perconditioning (Perc) applied at different time points along with the role of RISK, SAFE, STAT5 and eNOS pathways. Methods and results: Anesthetized rabbitswere subjected to 30-min ischemia/3-hour reperfusion. Perc, consisted of 4 cycles of 1-min ischemia/reperfusion, was applied in the carotid artery at different time points. Perc was started and ended during ischemia, started during ischemia and ended at the beginning of reperfusion, started at the end of ischemia and ended at reperfusion and started and ended during reperfusion. The PI3K inhibitor wortmannin, or the JAK-2 inhibitor AG490, was also applied and the infarct size was aßeßed. In another series aßigned to the previous groups, the phosphorylation of Akt, PI3K, ERKs1/2, GSK3β, STAT3, and STAT5 was evaluated. All Perc groups had smaller infarction compared to those without Perc, independently of PI3K or JAK-2 inhibition. STAT5 was the only molecule that was phosphorylated in parallel with cardioprotection. Since Src and angiotensin II mediate the STAT5 pathway, we administered the Scr inhibitor PP1 and the angiotensin II receptor antagonist valsartan. PP1 and valsartan prevented STAT5 phosphorylation, but did not abrogate the effect of Perc. Furthermore, the NOS inhibitor L-NAME was administered and abrogated the infarct size limiting effect of Perc. In parallel, the expreßion of cleaved caspase-3 was elevated only in the control and Perc-A-LNAME groups. Conclusion: Perc reduces infarction independently of RISK, SAFE and STAT5 pathways. Src kinase and angiotensin II play a predominant role in STAT5 activation. eNOSmay protect themyocardiumthrough inhibition of apoptosis. © 2015 Elsevier Ireland Ltd. All rights reserved."
}