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Updated: May 16, 2026
Induction of Myocardial Infarction and Myocardial Ischemia-Reperfusion Injury in Mice
Published on: January 19, 2022
miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models
Zhenwei Pan1, Xuelin Sun, Jinshuai Ren
1Department 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
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.
Insights
MicroRNA-1 (miR-1) exacerbates cardiac injury, but systemic knockdown using LNA-antimiR-1 therapy effectively protects against heart damage. This study provides in vivo evidence for miR-1
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- MicroRNA Therapeutics
Background:
- MicroRNAs (miRNAs) play a crucial role in regulating cardiac injury.
- Cardiac-enriched microRNA-1 (miR-1) is implicated in cardiac myocyte damage.
- In vivo evidence and therapeutic potential of miR-1 knockdown in cardiac injury remain underexplored.
Purpose of the Study:
- To investigate the in vivo role of miR-1 in cardiac ischemia/reperfusion (I/R) injury.
- To evaluate the therapeutic efficacy of systemic miR-1 knockdown using LNA-antimiR-1.
- To elucidate the molecular mechanisms underlying miR-1's effect on cardiac injury.
Main Methods:
- Utilized miR-1 transgenic (miR-1 Tg) mice and LNA-antimiR-1 treatment.
- Subjected mice to a cardiac I/R injury model (30 min ischemia, 24 h reperfusion).
- Assessed cardiac injury markers (LDH, CK, caspase-3, apoptosis, infarct size) and molecular targets (PKCε, HSP60) via luciferase assays.
Main Results:
- miR-1 overexpression in Tg mice worsened I/R injury, increasing cardiac damage markers and apoptosis.
- LNA-antimiR-1 treatment significantly attenuated I/R injury.
- miR-1 directly represses PKCε and HSP60 expression, while knockdown enhances them, indicating a molecular mechanism.
Conclusions:
- miR-1 is a causal factor in cardiac injury.
- Systemic LNA-antimiR-1 therapy demonstrates significant therapeutic potential for ameliorating cardiac I/R injury.
- Targeting miR-1 offers a promising therapeutic strategy for cardiovascular protection.
