PMID- 24978894 OWN - NLM STAT- MEDLINE DCOM- 20151014 LR - 20140815 IS - 1540-0514 (Electronic) IS - 1073-2322 (Linking) VI - 42 IP - 3 DP - 2014 Sep TI - Effects of remote ischemic preconditioning and myocardial ischemia on microRNA-1 expression in the rat heart in vivo. PG - 234-8 LID - 10.1097/SHK.0000000000000201 [doi] AB - Remote ischemic preconditioning (RIPC) is an easily applicable method for protecting the heart against a subsequent ischemia and reperfusion (I/R) injury. However, the exact molecular mechanisms underlying RIPC are unknown. We examined the involvement of microRNAs (miRNAs) and in particular the expression of miRNA-1 (miR-1) in RIPC and myocardial ischemia. Remote ischemic preconditioning was conducted by four cycles of 5-min bilateral hind-limb ischemia in male Wistar rats. Cardiac ischemia was induced by ligation of the left anterior descending coronary artery for 35 min followed by 2 or 6 h of reperfusion. MicroRNA expression was analyzed by Taqman miRNA arrays and quantitative polymerase chain reaction assays. Luciferase assays were performed to validate the miR-1 target gene brain-derived neurotrophic factor (BDNF). Brain-derived neurotrophic factor mRNA and protein levels were analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Remote ischemic preconditioning led to a differential expression of miRNAs. The most abundant cardiac miRNA, miR-1, was downregulated by RIPC without following ischemia as well as after I/R and RIPC followed by I/R after 2 h of reperfusion. After 6 h of reperfusion, RIPC led to an upregulation of miR-1, whereas ischemia had no effect on miR-1 expression. Luciferase assays confirmed the interaction of miR-1 with BDNF, a protein that has been shown to exert cardioprotective effects. Brain-derived neurotrophic factor protein levels in rat hearts measured by enzyme-linked immunosorbent assay were not significantly altered after 2 or 6 h of reperfusion in all intervention groups. Remote ischemic preconditioning leads to changes in the expression levels of the most abundant cardiac miRNA, miR-1. MicroRNA 1 levels did not correlate with protein levels of BDNF, a known miR-1 target, in vivo. Further studies are needed to explore the biological significance of changes in miR-1 expression levels and the potential interaction with BDNF in RIPC-induced cardioprotection. FAU - Brandenburger, Timo AU - Brandenburger T AD - *Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany; and daggerHadassah Medical School, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Grievink, Hilbert AU - Grievink H FAU - Heinen, Nicole AU - Heinen N FAU - Barthel, Franziska AU - Barthel F FAU - Huhn, Ragnar AU - Huhn R FAU - Stachuletz, Friederike AU - Stachuletz F FAU - Kohns, Malte AU - Kohns M FAU - Pannen, Benedikt AU - Pannen B FAU - Bauer, Inge AU - Bauer I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Shock JT - Shock (Augusta, Ga.) JID - 9421564 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (MIRN1 microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - EC 1.13.12.- (Luciferases) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Computational Biology MH - Disease Models, Animal MH - Gene Expression Profiling MH - Gene Expression Regulation MH - Genes, Reporter MH - HEK293 Cells MH - Hemodynamics MH - Hindlimb/*blood supply MH - Humans MH - Ischemic Preconditioning/*methods MH - Luciferases/biosynthesis/genetics MH - Male MH - MicroRNAs/genetics/*metabolism MH - Myocardial Reperfusion Injury/genetics/metabolism/pathology/physiopathology/*prevention & control MH - Myocardium/*metabolism/pathology MH - RNA, Messenger/metabolism MH - Rats, Wistar MH - Time Factors MH - Transfection EDAT- 2014/07/01 06:00 MHDA- 2015/10/16 06:00 CRDT- 2014/07/01 06:00 PHST- 2014/07/01 06:00 [entrez] PHST- 2014/07/01 06:00 [pubmed] PHST- 2015/10/16 06:00 [medline] AID - 10.1097/SHK.0000000000000201 [doi] PST - ppublish SO - Shock. 2014 Sep;42(3):234-8. doi: 10.1097/SHK.0000000000000201.