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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Yu Chen & Shuai Liu & Yunsong Liang & Yutong He & Qian Li & Jiamian Zhan & Honghao Hou & Xiaozhong Qiu, 2024. "Single dose of intravenous miR199a-5p delivery targeting ischemic heart for long-term repair of myocardial infarction," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49901-x
    DOI: 10.1038/s41467-024-49901-x
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    References listed on IDEAS

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    1. Ana Eulalio & Miguel Mano & Matteo Dal Ferro & Lorena Zentilin & Gianfranco Sinagra & Serena Zacchigna & Mauro Giacca, 2012. "Functional screening identifies miRNAs inducing cardiac regeneration," Nature, Nature, vol. 492(7429), pages 376-381, December.
    2. Xian Yu & Xiao Chen & Mamta Amrute-Nayak & Edward Allgeyer & Aite Zhao & Hannah Chenoweth & Marc Clement & James Harrison & Christian Doreth & George Sirinakis & Thomas Krieg & Huiyu Zhou & Hongda Hua, 2021. "MARK4 controls ischaemic heart failure through microtubule detyrosination," Nature, Nature, vol. 594(7864), pages 560-565, June.
    3. Ge Tao & Peter C. Kahr & Yuka Morikawa & Min Zhang & Mahdis Rahmani & Todd R. Heallen & Lele Li & Zhao Sun & Eric N. Olson & Brad A. Amendt & James F. Martin, 2016. "Pitx2 promotes heart repair by activating the antioxidant response after cardiac injury," Nature, Nature, vol. 534(7605), pages 119-123, June.
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