[HTML][HTML] miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models

Z Pan, X Sun, J Ren, X Li, X Gao, C Lu, Y Zhang… - PloS one, 2012 - journals.plos.org
Z Pan, X Sun, J Ren, X Li, X Gao, C Lu, Y Zhang, H Sun, Y Wang, H Wang, J Wang, L Xie…
PloS one, 2012journals.plos.org
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 …
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.
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