6. Conclusions & Perspectives
We have reported herein a glimpse of the value that microRNA microarrays can provide to understand the role of microRNAs in cardiovascular development. A simple approach, comparison of the microRNA signature of the developing ventricular chambers, has highlighted that almost 50% of the differentially expressed microRNAs identified have been subsequently shown to play diverse functional roles in the cardiovascular system. Moreover, meta-analyses comparing two additional conditions revealed similar microRNA signatures in the developing cardiac chambers and the differentiating and maturing cardiomyocytes derived from induced pluripotent stem cells, which are not altered in the adult and aging heart. Furthermore, such a proof-of-principle microRNA microarray meta-analyses provide also novel hints, as decoding a subset of microRNAs that behave in the opposite pattern during in vitro (iPS-derived) and in vivo (chamber maturation) cardiogenesis, opening new avenues to dissect the functional role of these microRNAs in the cardiovascular setting. Moreover, future meta-analyses studies, including not only healthy conditions, but emerging microRNA signatures of diseased status, such as atrial fibrillation, cardiac hypertrophy or ischemia, will certainly increase our understanding of microRNA biology in the normal and diseased heart. In addition, microRNA microarrays also provided novel insights into the intricate biology of microRNA transcriptional regulation and putative target recognition, broadening, thus, the spectrum of their applicability.
As we focus our attention on the developing heart, it is becoming clear that microRNAs play a pivotal role in cardiac muscle biology, the interstitial tissue and also valve development. Yet, one of the challenges that remains ahead of us is to fine-tune our understanding of microRNA function in distinct cardiovascular settings, starting from unravelling their tissue distribution and following with dissecting the role of microRNAs in the epicardium and coronary vasculature. Such endeavors will provide us novel understandings and tools for promising therapeutic usage.