Abstract
Cardiovascular development is a complex developmental process starting with the formation of an early straight heart tube, followed by a rightward looping and the configuration of atrial and ventricular chambers. The subsequent step allows the separation of these cardiac chambers leading to the formation of a four-chambered organ. Impairment in any of these developmental processes invariably leads to cardiac defects. Importantly, our understanding of the developmental defects causing cardiac congenital heart diseases has largely increased over the last decades. The advent of the molecular era allowed to bridge morphogenetic with genetic defects and therefore our current understanding of the transcriptional regulation of cardiac morphogenesis has enormously increased. Moreover, the impact of environmental agents to genetic cascades has been demonstrated as well as of novel genomic mechanisms modulating gene regulation such as post-transcriptional regulatory mechanisms. Among post-transcriptional regulatory mechanisms, non-coding RNAs, including therein microRNAs and lncRNAs, are emerging to play pivotal roles. In this review, we summarize current knowledge on the functional role of non-coding RNAs in distinct congenital heart diseases, with particular emphasis on microRNAs and long non-coding RNAs.
Highlights
Cardiovascular development is a complex developmental process involving the formation and alignment of distinct cell sources
In addition to transcriptional regulation of the developing cardiovascular system, increasing evidence demonstrates a substantial contribution of post-transcriptional mechanisms, such as those driven by non-coding RNAs
Experimental genetic manipulation of several microRNAs led to congenital heart diseases (CHD) such as double outlet right ventricle (DORV) and VSD highlighting the importance of these non-coding RNAs in cardiogenesis
Summary
Cardiovascular development is a complex developmental process involving the formation and alignment of distinct cell sources. We provide a systematic review of the current understanding of the functional role of microRNAs on the pathogenesis of cardiac CHD within the three major CHD subtypes, cyanotic heart disease, left-sided obstruction defects, and septation defects.
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