The role of miRNA regulation in fetal cardiomyocytes, cardiac maturation and the risk of heart disease in adults

Mitchell C. Lock, Ross L Tellam, Kimberley C W Wang, Kimberley J Botting, Joseph Selvanayagam, Douglas A Brooks, Mike Seed, Janna L Morrison

Research output: Contribution to specialist publicationArticle

13 Citations (Scopus)

Abstract

Myocardial infarction is a primary contributor towards the global burden of cardiovascular disease. Rather than repairing the existing damage of myocardial infarction, current treatments only address the symptoms of the disease and reducing the risk of a secondary infarction. Cardiac regenerative capacity is dependent on cardiomyocyte proliferation, which concludes soon after birth in humans and precocial species such as sheep. Human fetal cardiac tissue has some ability to repair following tissue damage, whereas a fully matured human heart has minimal capacity for cellular regeneration. This is in contrast to neonatal mice and adult zebrafish hearts, which retain the ability to undergo cardiomyocyte proliferation and can regenerate cardiac tissue after birth. In mice and zebrafish models, microRNAs (miRNAs) have been implicated in the regulation of genes involved in cardiac cell cycle progression and regeneration. However, the significance of miRNA regulation in cardiomyocyte proliferation for humans and other large mammals, where the timing of heart development in relation to birth is similar, remains unclear. miRNAs may be valuable targets for therapies that promote cardiac repair after injury. Therefore, elucidating the role of specific miRNAs in large animals, where heart development closely resembles that of humans, remains vitally important for identifying therapeutic targets that may be translated into clinical practice focused on tissue repair.

Original languageEnglish
Pages5625-5640
Number of pages16
Volume596
No.23
Specialist publicationJournal of Physiology
DOIs
Publication statusPublished - 1 Dec 2018

Keywords

  • epigenetics
  • fetal development
  • heart attack
  • heart disease
  • miRNA
  • programming
  • regeneration

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    Lock, M. C., Tellam, R. L., Wang, K. C. W., Botting, K. J., Selvanayagam, J., Brooks, D. A., Seed, M., & Morrison, J. L. (2018). The role of miRNA regulation in fetal cardiomyocytes, cardiac maturation and the risk of heart disease in adults. Journal of Physiology, 596(23), 5625-5640. https://doi.org/10.1113/JP276072