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.
Highlights
MicroRNAs are a group of single strand non-coding RNAs that inhibit the translation of protein-coding genes by annealing inexactly to complementary sequences in the 39UTRs of target mRNAs [1]
The expression of miR-1 was strongly increased in both serum, cardiac tissues and cultured cardiac myocytes during cardiac injury induced by various stimuli [6,7,9,11]
Serum miR-1 level is increased after myocardial infarction, which strongly correlates with infarct size and can be significantly reduced by ischemic preconditioning [14]
Summary
MicroRNAs (miRNAs) are a group of single strand non-coding RNAs that inhibit the translation of protein-coding genes by annealing inexactly to complementary sequences in the 39UTRs of target mRNAs [1]. Recent studies indicated that miRNAs are broadly involved in the development of cardiovascular diseases, including arrhythmia, hypertrophy, heart failure and cardiac injury etc [2]. The regulatory action of miRNAs is often physiologically significant that modulation of expression of a single miRNA could change a specific pathological process [2]. The muscle-specific miRNA miR-1 is one of the miRNAs shown to play a role in cardiac injury [5,6,7]. MiR-1 is the first miRNA that has been extensively explored and confirmed to be a key regulator of cardiac development and disease [7,8,9,10,11]. Zhao et al found that miR-1 participates in cardiogenesis by regulating the expression of a transcription factor
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
