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: Zhenwei Pan, Xuelin Sun, Jinshuai Ren, Xin Li, Xu Gao, Chunying Lu, Yang Zhang, Hui Sun, Ying Wang, Huimin Wang, Jinghao Wang, Liangjun Xie, Yanjie Lu, Baofeng Yang
• Journal: PloS one (PLoS One) Vol. 7 Issue 11 Pg. e50515 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23226300 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chaperonin 60
• MicroRNAs
• Mirn1 microRNA, mouse
• Oligonucleotides
• locked nucleic acid
• L-Lactate Dehydrogenase
• Protein Kinase C-epsilon
• Creatine Kinase
• Caspase 3

Topics

• Animals
• Apoptosis
• Base Sequence
• Caspase 3 (metabolism)
• Chaperonin 60 (genetics, metabolism)
• Creatine Kinase (metabolism)
• Disease Models, Animal
• Gene Expression Regulation
• Gene Knockdown Techniques
• Humans
• L-Lactate Dehydrogenase (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• MicroRNAs (genetics, metabolism)
• Myocardial Infarction (complications)
• Myocardial Ischemia (complications)
• Myocytes, Cardiac (metabolism, pathology)
• Oligonucleotides (genetics)
• Protein Kinase C-epsilon (genetics, metabolism)
• Reperfusion Injury (complications, genetics, metabolism, pathology)