Fig. 2.

Regulatory networks controlled by miR-143/145 in cardiovascular development and disease in vSMCs.

Schematic illustration of the main pathways regulated by miR-143/145 in vSMCs. During development, miR-143/145 show high expression levels in the myocardium of mouse embryo (E7-E9). In late cardiogenesis, expression mainly correlates with the ventricles and atria (E15). The expression pattern is then inverted post-natally, where miR-143/145 is expressed only in the aorta and pulmonary arteries. In physiological conditions in adult mouse, the vascular-specific microRNA cluster controls the transcription of contractility and differentiation genes typical of a SMC signature (α-SMA, Calponin, Mhy11). Particularly, the transcriptional regulation of vSMC contractile phenotype involves binding of SRF/Myocd (Serum Responsive Factor/Myocardin) to the CArG box located on the promoter of contractility genes, which in turn induce the miR-143/145 expression. Importantly, miR-143/145 is also implicated in the regulation of the vSMCs phenotypic switch in vascular disease. Particularly, miR-143/145 was found dysregulated in response to vascular injury, such as hypoxia, stretch, shear stress, growth factors, pro-inflammatory cytokines, inducing genes regulating vSMC proliferation, migration and plasticity [12].