Functional Screening Identifies miRNAs Inducing Cardiac Regeneration

Medical advances in the regeneration of heart tissue damaged from cardiac infarction and heart disease could have profound implications in the treatment of patients with these conditions. A recent study published last month in Nature, entitled Functional screening identifies miRNAs inducing cardiac regeneration, uses a human miRNA library screen to identify functional miRNA gene candidates than can induce cardiomyocytes to re-enter the cell cycle and proliferate. Eulalio et. al have identified two human miRNA genes, hsa-miR-590 and hsa-miR-199a, that can induce proliferation of post-natal cardiomyocytes in rat and mouse and mimics of both were injected in vivo into the hearts of neonatal rats. Researchers observed after three days post-injection an increase in proliferating cardiomyocytes with no increase in fibrosis within the rat heart tissue; indicating the cell-specific effect in the usage of miRs-590 and 199a. Additionally, Eulalio et. al used a viral vector to over-express miR-590 and miR-199a in neonatal mice over a 12 day period. Researchers noted enlargement of the mouse hearts, but these were morphologically normal with a significantly increased rate of proliferation of cardiomyocytes.

The concluding investigations in this article, and perhaps the most exciting from a translational perspective, are the evidence that viral expression of both miRNA genes in mouse hearts, after cardiac infarction, significantly reduced the infarct size while increasing cardiac function in vivo. These effects were still noticeable 60-days post infarction. This is the first study detailing the over-expression of miRNA genes to reduce the affects of heart attack and outlines a possible mechanism in the treatment of heart disease via the stimulation of cardiomyocyte proliferation using miRNA.

Intriguingly, Eulalio et. al may have additionally outlined a blue-print for the identification and validation of miRNA gene therapies not only for heart disease, but for other tissues as well. The regeneration of tissues via the usage of miRNA genes could be vitally important for other diseases such as Alzheimer’s, traumatic brain injury, ALS, and other tissue degenerative diseases and conditions.  The authors conclude their investigation by commenting that their investigations might be useful in combination with already established procedures using cardiac stem cells to induce cardiomyocyte proliferation and regeneration in the heart.

Eulalio, Ana., Mano, Miguel., Dal Ferro, Matteo., Zentillin, Lorena., Sinagra, Gianfranco., Zacchigna, Serana., and Mauro Giacca.
Functional screening identifies miRNAs inducing cardiac regeneration.
2012; Vol. 491, pg. 377-381.

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