Functions of miRNAs during Mammalian Heart Development

Abstract

MicroRNAs (miRNAs) play essential roles during mammalian heart development and have emerged as attractive therapeutic targets for cardiovascular diseases. The mammalian embryonic heart is mainly derived from four major cell types during development. These include cardiomyocytes, endocardial cells, epicardial cells, and neural crest cells. Recent data have identified various miRNAs as critical regulators of the proper differentiation, proliferation, and survival of these cell types. In this review, we briefly introduce the contemporary understanding of mammalian cardiac development. We also focus on recent developments in the field of cardiac miRNAs and their functions during the development of different cell types.

Clustered miRNAs and their role in biological functions and diseases

“…miR-302/367 affects stem cell properties during expression at the early embryonic stage, and shows differential expression between mouse embryonic stem cells (mESCs) and human embryonic stem cells (hESCs) (Dyce, Toms & Li, 2010). Similarly, regulation by miR-17/92 is reported during cardiomyocyte proliferation (Yan & Jiao, 2016). miR-23/24 clusters play a critical role in T-cell differentiation (Kroesen et al, 2015) and miR-206/133b cluster is important for skeletal muscle development, regeneration and differentiation (Boettger et al, 2014).…”

Epigenetic responses and the developmental origins of health and disease

“…Studies from several other laboratories have also demonstrated that miRNAs are associated with developmental programming of various organs (Zucchi et al 2013, Casas-Agustench et al 2015. The organs and tissues investigated include heart (Yan & Jiao 2016, Lock et al 2017), brain (Petri et al 2014) and several endocrine glands (pancreas, ovary, testes, hypothalamus and pituitary) (Kredo-Russo et al 2012, Voglova et al 2016. Of note, exposure to environmental toxins during human pregnancy affects miRNA expression in cord blood, which lead to increased disease susceptibility in offspring (Rager et al 2014, Gillet et al 2016).…”

Acute molecular effects of pressure‐controlled intermittent coronary sinus occlusion in patients with advanced heart failure

“…5 A number of studies demonstrated that elevated levels of miR-143 and miR-145 play an important role in regulating several transcription factors like octamer-binding transcription factor 4, sex-determining region Y-box 2, and Krüppellike factor 4 (KLF-4) as well as promoting differentiation and simultaneously repressing proliferation of vascular smooth muscle cells. Regulation of cardiogenic gene expression by microRNA has been shown to play a prominent role in heart development.…”

“…The potential of influencing microRNA expression may therefore be utilized in management and prevention of cardiovascular diseases. 5 A number of studies demonstrated that elevated levels of miR-143 and miR-145 play an important role in regulating several transcription factors like octamer-binding transcription factor 4, sex-determining region Y-box 2, and Krüppellike factor 4 (KLF-4) as well as promoting differentiation and simultaneously repressing proliferation of vascular smooth muscle cells. The significant increase in plasma levels of miR-143 and miR-145 in PICSO-treated patients together with the significant up-regulation of KLF-4 is suggestive of activation of such pathways.…”