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MicroRNAs associated with ischemia-reperfusion injury and cardioprotection by ischemic pre- and postconditioning: protectomiRs

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


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{
  "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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