title: miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models.
abstract: Recent studies have revealed the critical role of microRNAs (miRNAs) in regulating cardiac injury. Among them, the cardiac enriched microRNA-1(miR-1) has been extensively investigated and proven to be detrimental to cardiac myocytes. However, solid in vivo evidence for the role of miR-1 in cardiac injury is still missing and the potential therapeutic advantages of systemic knockdown of miR-1 expression remained unexplored. In this study, miR-1 transgenic (miR-1 Tg) mice and locked nucleic acid modified oligonucleotide against miR-1 (LNA-antimiR-1) were used to explore the effects of miR-1 on cardiac ischemia/reperfusion injury (30 min ischemia followed by 24 h reperfusion). The cardiac miR-1 level was significantly increased in miR-1 Tg mice, and suppressed in LNA-antimiR-1 treated mice. When subjected to ischemia/reperfusion injury, miR-1 overexpression exacerbated cardiac injury, manifested by increased LDH, CK levels, caspase-3 expression, apoptosis and cardiac infarct area. On the contrary, LNA-antimiR-1 treatment significantly attenuated cardiac ischemia/reperfusion injury. The expression of PKCε and HSP60 was significantly repressed by miR-1 and enhanced by miR-1 knockdown, which may be a molecular mechanism for the role miR-1 in cardiac injury. Moreover, luciferase assay confirmed the direct regulation of miR-1 on protein kinase C epsilon (PKCε) and heat shock protein 60 (HSP60). In summary, this study demonstrated that miR-1 is a causal factor for cardiac injury and systemic LNA-antimiR-1 therapy is effective in ameliorating the problem.
authors.affiliation: Department of Pharmacology-Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China. panzw@ems.hrbmu.edu.cn
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Pan
authors.forename: Xuelin
authors.initials: X
authors.lastname: Sun
authors.forename: Jinshuai
authors.initials: J
authors.lastname: Ren
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
authors.forename: Chunying
authors.initials: C
authors.lastname: Lu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Huimin
authors.initials: H
authors.lastname: Wang
authors.forename: Jinghao
authors.initials: J
authors.lastname: Wang
authors.forename: Liangjun
authors.initials: L
authors.lastname: Xie
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Lu
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D053148:Caspase 3 / Q000378:metabolism; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000150:complications; D017202:Myocardial Ischemia / Q000150:complications*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009841:Oligonucleotides / Q000235:genetics; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018834:Chaperonin 60; D035683:MicroRNAs; C517731:Mirn1 microRNA, mouse; D009841:Oligonucleotides; C477371:locked nucleic acid; D007770:L-Lactate Dehydrogenase; D051744:Protein Kinase C-epsilon; D003402:Creatine Kinase; D053148:Caspase 3