Single dose of intravenous miR199a-5p delivery targeting ischemic heart for long-term repair of myocardial infarction

Yu Chen, Shuai Liu, Yunsong Liang, Yutong He, Qian Li, Jiamian Zhan, Honghao Hou () and Xiaozhong Qiu ()
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Yu Chen: Southern Medical University
Shuai Liu: Southern Medical University
Yunsong Liang: Southern Medical University
Yutong He: Southern Medical University
Qian Li: Southern Medical University
Jiamian Zhan: Southern Medical University
Honghao Hou: Southern Medical University
Xiaozhong Qiu: Southern Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Long-term treatment of myocardial infarction is challenging despite medical advances. Tissue engineering shows promise for MI repair, but implantation complexity and uncertain outcomes pose obstacles. microRNAs regulate genes involved in apoptosis, angiogenesis, and myocardial contraction, making them valuable for long-term repair. In this study, we find downregulated miR-199a-5p expression in MI. Intramyocardial injection of miR-199a-5p into the infarcted region of male rats revealed its dual protective effects on the heart. Specifically, miR-199a-5p targets AGTR1, diminishing early oxidative damage post-myocardial infarction, and MARK4, which influences long-term myocardial contractility and enhances cardiac function. To deliver miR-199a-5p efficiently and specifically to ischemic myocardial tissue, we use CSTSMLKAC peptide to construct P-MSN/miR199a-5p nanoparticles. Intravenous administration of these nanoparticles reduces myocardial injury and protects cardiac function. Our findings demonstrate the effectiveness of P-MSN/miR199a-5p nanoparticles in repairing MI through enhanced contraction and anti-apoptosis. miR199a-5p holds significant therapeutic potential for long-term repair of myocardial infarction.

Date: 2024
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DOI: 10.1038/s41467-024-49901-x

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