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Varga, Zoltan V.; Zvara, Agnes; Farago, Nora; Kocsis, Gabriella F.; Pipicz, Marton; Gaspar, Renata; Bencsik, Peter; Goerbe, Aniko; Csonka, Csaba; Puskas, Laszlo G.; Thum, Thomas; Csont, Tamas; Ferdinandy, Peter
{ "DOI": "10.1152/ajpheart.00812.2013", "abstract": "We aimed to characterize early changes in microRNA expression in acute cardioprotection by ischemic pre- and postconditioning in rat hearts. Hearts isolated from male Wistar rats were subjected to 1) time-matched nonischemic perfusion, 2) ischemia-reperfusion (30 min of coronary occlusion and 120 min of reperfusion), 3) preconditioning (3 x 5 min of coronary occlusion) followed by ischemia-reperfusion, or 4) ischemia-reperfusion with postconditioning (6 x 10 s of global ischemia-reperfusion at the onset of reperfusion). Infarct size was significantly reduced by both interventions. Of 350 different microRNAs assessed by microarray analysis, 147-160 microRNAs showed detectable expression levels. Compared with microRNA alterations induced by ischemia-reperfusion versus time-matched nonischemic controls, five microRNAs were significantly affected by both pre- and postconditioning (microRNA-125b*, microRNA-139-3p, microRNA-320, microRNA-532-3p, and microRNA-188), four microRNAs were significantly affected by preconditioning (microRNA-487b, microRNA-139-5p, microRNA-192, and microRNA-212), and nine microRNAs were significantly affected by postconditioning (microRNA-1, microRNA let-7i, microRNA let-7e, microRNA let-7b, microRNA-181a, microRNA-208, microRNA-328, microRNA-335, and microRNA-503). Expression of randomly selected microRNAs was validated by quantitative real-time PCR. By a systematic comparison of the direction of microRNA expression changes in all groups, we identified microRNAs, specific mimics, or antagomiRs that may have pre- and postconditioning-like cardioprotective effects (protectomiRs). Transfection of selected protectomiRs (mimics of microRNA-139-5p, microRNA-125b*, microRNA let-7b, and inhibitor of microRNA-487b) into cardiac myocytes subjected to simulated ischemia-reperfusion showed a significant cytoprotective effect. This is the first demonstration that the ischemia-reperfusion-induced microRNA expression profile is significantly influenced by both pre- and postconditioning, which shows the involvement of microRNAs in cardioprotective signaling. Moreover, by analysis of microRNA expression patterns in cardioprotection by pre- and postconditioning, specific protectomiRs can be revealed as potential therapeutic tools for the treatment of ischemia-reperfusion injury.", "author": [ { "family": "Varga", "given": " Zoltan V." }, { "family": "Zvara", "given": " Agnes" }, { "family": "Farago", "given": " Nora" }, { "family": "Kocsis", "given": " Gabriella F." }, { "family": "Pipicz", "given": " Marton" }, { "family": "Gaspar", "given": " Renata" }, { "family": "Bencsik", "given": " Peter" }, { "family": "Goerbe", "given": " Aniko" }, { "family": "Csonka", "given": " Csaba" }, { "family": "Puskas", "given": " Laszlo G." }, { "family": "Thum", "given": " Thomas" }, { "family": "Csont", "given": " Tamas" }, { "family": "Ferdinandy", "given": " Peter" } ], "container_title": "AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY", "id": "63873", "issue": "2", "issued": { "date-parts": [ [ 2014, 1, 1 ] ] }, "page": "H216-H227", "title": "MicroRNAs associated with ischemia-reperfusion injury and cardioprotection by ischemic pre- and postconditioning: protectomiRs", "type": "article-journal", "volume": "307" }
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