Noncoding RNAs regulating cardiac muscle mass

Author:

Wadley Glenn D.1ORCID,Lamon Séverine1ORCID,Alexander Sarah E.1,McMullen Julie R.23456,Bernardo Bianca C.237

Affiliation:

1. Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Australia

2. Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia

3. Department of Diabetes, Central Clinical School, Monash University, Clayton, Victoria, Australia

4. Department of Medicine, Monash University, Clayton, Victoria, Australia

5. Department of Physiology, Monash University, Clayton, Victoria, Australia

6. Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Victoria, Australia

7. Department of Paediatrics, University of Melbourne, Victoria, Australia

Abstract

Noncoding RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) play roles in the development and homeostasis of nearly every tissue of the body, including the regulation of processes underlying heart growth. Cardiac hypertrophy can be classified as either physiological (beneficial heart growth) or pathological (detrimental heart growth), the latter of which results in impaired cardiac function and heart failure and is predictive of a higher incidence of death due to cardiovascular disease. Several miRNAs have a functional role in exercise-induced cardiac hypertrophy, while both miRNAs and lncRNAs are heavily involved in pathological heart growth and heart failure. The latter have the potential to act as an endogenous sponge RNA and interact with specific miRNAs to control cardiac hypertrophy, adding another level of complexity to our understanding of the regulation of cardiac muscle mass. In addition to tissue-specific effects, ncRNA-mediated tissue cross talk occurs via exosomes. In particular, miRNAs can be internalized in exosomes and secreted from various cardiac and vascular cell types to promote angiogenesis, as well as protection and repair of ischemic tissues. ncRNAs hold promising therapeutic potential to protect the heart against ischemic injury and aid in regeneration. Numerous preclinical studies have demonstrated the therapeutic potential of ncRNAs, specifically miRNAs, for the treatment of cardiovascular disease. Most of these studies employ antisense oligonucleotides to inhibit miRNAs of interest; however, off-target effects often limit their potential to be translated to the clinic. In this context, approaches using viral and nonviral delivery tools are promising means to provide targeted delivery in vivo.

Funder

The Baker Foundation

Department of Health, Australian Government | National Health and Medical Research Council (NHMRC)

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology

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