miR-1 Exacerbates Cardiac Ischemia-Reperfusion Injury in Mouse Models

被引:98
作者
Pan, Zhenwei [1 ]
Sun, Xuelin [1 ]
Ren, Jinshuai [1 ]
Li, Xin [1 ]
Gao, Xu [2 ]
Lu, Chunying [1 ]
Zhang, Yang [1 ]
Sun, Hui [1 ]
Wang, Ying [1 ]
Wang, Huimin [1 ]
Wang, Jinghao [1 ]
Xie, Liangjun [1 ]
Lu, Yanjie [1 ]
Yang, Baofeng [1 ]
机构
[1] Harbin Med Univ, Dept Pharmacol, Key Lab Cardiovasc Med Res, Minist Educ,State Prov Key Labs Biomed Pharmaceut, Harbin, Heilongjiang, Peoples R China
[2] Harbin Med Univ, Dept Biochem, Harbin, Heilongjiang, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
MUSCLE-SPECIFIC MICRORNA; MYOCARDIAL-INFARCTION; HEAT-SHOCK; IN-VIVO; HSP60; CARDIOMYOCYTES; EXPRESSION; PROTECTION; APOPTOSIS; EPSILON;
D O I
10.1371/journal.pone.0050515
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 PKC epsilon 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 (PKC epsilon) 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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页数:9
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