Impact of miR-1/miR-133 Cluster in Cardiogenesis and Heart Failure

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Abstract
Cardiogenesis is initiated soon during gastrulation as bilateral precardiac mesoderm, progressive and symmetrically determined at both sides of the developing embryo. The precardiac mesoderm subsequently fuse at the embryonic midline constituting an embryonic linear heart tube. As development progress, the embryonic tube heart suffers an invariably rightward looping generating a prospective embryonic ventricular and atrial chambers. As cardiac development progresses, the primitive atrial and ventricular chambers enlarged and distinct left and right compartments emerge by formation of the interatrial and interventricular septa, respectively. The last steps of cardiac morphogenesis are represented by the completion of atrial and ventricular septation, resulting in the configuration of a double circuitry with distinct systemic and pulmonary chambers, each of them with distinct inlets and outlets connections. The heart development is resulted of the activation and repression of several cardiac specific gene programs in different cell types. These cardiac specific gene pathways are modulated at transcriptional and post-transcriptional levels by key cardiac transcription factors and different paracrine and autocrine signals. Over the last decade, a novel layer of complexity has emerged with the discovery of non-coding RNAs, particularly microRNAs and lncRNAs. MicroRNAs are endogenous ≈22-nt non-coding RNAs that participate in the regulation of gene expression at post-transcriptional level on most cellular processes. In this line, miR-1/miR-133 cluster is one of the muscle-specific cluster microRNAs. Proper expression of members of this cluster is essential for cardiogenesis. Furthermore, dysregulation expression of miR-1 and miR-133 expression exerts an important role in heart failure and related pathological processes. Herein, we provide a state-of-the-art review of the contribution of miR-1/miR-133 cluster in cardiogenesis and heart failure development.

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