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A novel microRNA based therapeutic strategy for ischemic heart repair?

Paper commented by the ESC WG on Cellular Biology of the Heart

Basic Science - Cardiac Diseases - Ischemia, Infarction, Cardioprotection
Cardiac Diseases


For years there have been efforts to improve/stimulate the intrinsically very limited renewal capacity of adult cardiomyocytes. So far with very limited success.

In the actual issue of Basic Research in Cardiology, Jung et al. propose a novel microRNA based strategy for ischemic heart repair. The initially observe, that human pluripotent stem cells release a very large amount of extracellular vesicles - when cultivated under hypoxia. Under these conditions in the released vesicles the microRNAs 20b, 92a and 363 are enriched.

In a mouse model of permanent ligation, the authors were able to explore the therapeutic potential of the microRNA enriched vesicles”. The authors compare effect of their extracellular vesicles with microRNAs 20b, 92a and 363 enriched biodegradable polymer vesicles. They inject the vesicles, respectively, into the infarct border zone after myocardial infarction at 2 and 4 weeks. Left ventricular function and myocardial fibrosis was reduced in those groups treated with the vesicles.

The authors propose a mechanistic route of action: the microRNAs stimulated cardiomyocyte proliferation in the infarct border zone triggers endogenous self-repair pathways in the heart. In RNA-seq analysis, the authors were able to identify Jag1-Notch3-Hes1 pathway as an intracellular target of the microRNAs 20b, 92a and 363 cluster. Cell cycle activator and cytokines genes were also significantly up-regulated.

References


MiR-106a–363 cluster in extracellular vesicles promotes endogenous myocardial repair via Notch3 pathway in ischemic heart injury.

Ji-Hye Jung, Gentaro Ikeda, Yuko Tada, Daniel von Bornstädt, Michelle R. Santoso, Christine Wahlquist, Siyeon Rhee, Young-Jun Jeon, Anthony C. Yu, Connor G. O’brien, Kristy Red-Horse, Eric A. Appel, Mark Mercola, Joseph Woo & Phillip C. Yang

Basic Res Cardiol 116, 19 (2021). https://doi.org/10.1007/s00395-021-00858-8

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

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