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The Promise of MicroRNA Therapy to Stimulates Uncontrolled Cardiac Repair in Animal Trials of Large Mammals


The Promise of MicroRNA Therapy to Stimulates Uncontrolled Cardiac Repair in Animal Trials of Large Mammals

 

Reporter: Aviva Lev-Ari, PhD, RN

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Here we show that expression of human microRNA-199a in infarcted pig hearts can stimulate cardiac repair. One month after myocardial infarction and delivery of this microRNA through an adeno-associated viral vector, treated animals showed marked improvements in both global and regional contractility, increased muscle mass and reduced scar size. These functional and morphological findings correlated with cardiomyocyte de-differentiation and proliferation. However, subsequent persistent and uncontrolled expression of the microRNA resulted in sudden arrhythmic death of most of the treated pigs. Such events were concurrent with myocardial infiltration of proliferating cells displaying a poorly differentiated myoblastic phenotype.

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Abstract

Prompt coronary catheterization and revascularization have markedly improved the outcomes of myocardial infarction, but have also resulted in a growing number of surviving patients with permanent structural damage of the heart, which frequently leads to heart failure. There is an unmet clinical need for treatments for this condition1, particularly given the inability of cardiomyocytes to replicate and thereby regenerate the lost contractile tissue2. Here we show that expression of human microRNA-199a in infarcted pig hearts can stimulate cardiac repair. One month after myocardial infarction and delivery of this microRNA through an adeno-associated viral vector, treated animals showed marked improvements in both global and regional contractility, increased muscle mass and reduced scar size. These functional and morphological findings correlated with cardiomyocyte de-differentiation and proliferation. However, subsequent persistent and uncontrolled expression of the microRNA resulted in sudden arrhythmic death of most of the treated pigs. Such events were concurrent with myocardial infiltration of proliferating cells displaying a poorly differentiated myoblastic phenotype. These results show that achieving cardiac repair through the stimulation of endogenous cardiomyocyte proliferation is attainable in large mammals, however dosage of this therapy needs to be tightly controlled.

References

  1. 1.

    Roth, G. A. et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J. Am. Coll. Cardiol70, 1–25 (2017).

  2. 2.

    Eschenhagen, T. et al. Cardiomyocyte regeneration: a consensus statement. Circulation 136, 680–686 (2017).

SOURCE

https://www.nature.com/articles/s41586-019-1191-6

 

ALTERNATIVE methods of Cardiac Repair were published in this Open Access Online Scientific Journal:

 

Stem Cells and Cardiac Repair: Content Curation & Scientific Reporting: Aviva Lev-Ari, PhD, RN

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/04/17/stem-cells-and-cardiac-repair-content-curation-scientific-reporting-aviva-lev-ari-phd-rn/

 

Arteriogenesis and Cardiac Repair: Two Biomaterials – Injectable Thymosin beta4 and Myocardial Matrix Hydrogel

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/02/27/arteriogenesis-and-cardiac-repair-two-biomaterials-injectable-thymosin-beta4-and-myocardial-matrix-hydrogel/

 

Human Embryonic-Derived Cardiac Progenitor Cells for Myocardial Repair

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

https://pharmaceuticalintelligence.com/2012/08/01/human-embryonic-derived-cardiac-progenitor-cells-for-myocardial-repair/

 

 

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One Response

  1. on May 16, 2019 at 12:33 AM | Reply sjwilliamspa

    Interesting how in large animal models this problem was seen but not in lower rodent models. Another reason why large animal models are a big thing now.



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