**8. miRNA regulation of VSMC phenotype**

VSMC exhibit remarkable plasticity by adapting to local conditions via phenotypic modula‐ tion. Phenotypic modulation of VSMC is a highly complex process regulated by transcription factors and other gene products and multiple pathways that are still vaguely understood. Recently several reports have demonstrated the involvement of miRNA-mediated gene silencing in the regulation of VSMC proliferation, migration and differentiation in normal vascular development and in vascular pathologies. A list of a few selected miRNAs that regulate VSMC proliferation and differentiation in cell cultures and animal models with angioplasty is shown in Table 1 along with factors that regulate miRNA expression, their validated target proteins and function of the target proteins. While some of these miRNAs promote VSMC proliferation, others stimulate differentiation.


**Table 1.** miRNAs regulating vascular smooth muscle cell phenotype

gy can be validated by knocking out the miRNA processing enzyme Dicer in VSMC. To demonstrate the importance of miRNAs in VSMC development and function, a smooth muscle restricted -Dicer knockout model, SM-Dicer KO mice, is investigated recently [59,61]. Outcomes of the study indicate deletion of Dicer causes embryonic lethality due to de‐ creased VSMC proliferation and differentiation resulting in thinner vessel walls, impaired contractility and hemorrhage as well as reduced expression of VSMC-specific genes and proteins [59, 61]. Overall, these observations suggest that Dicer-generated miRNAs are cru‐

**Figure 1. Biogenesis of miRNA and gene silencing pathway.** The miRNA synthesis starts in the nucleus where primiRNA transcript is cleaved by Drosha/ DGCR8 to form ~60-100 nucleotides long hairpin loop pre-miRNA. Pre-miRNA is then transported to cytoplasm through the mediation of Exportin5 and Ran-GTP6 where it is further processed by RNase activity of Dicer to ~22 nucleotides mature miRNA duplex. The miRNA duplex then loads onto Ago in the RISC complex and undergoes strand separation. The guide strand of the miRNA mediates gene silencing by degrading the

VSMC exhibit remarkable plasticity by adapting to local conditions via phenotypic modula‐ tion. Phenotypic modulation of VSMC is a highly complex process regulated by transcription

target mRNA or interfering with translational process. The passenger strand gets degraded.

**8. miRNA regulation of VSMC phenotype**

cial for normal VSMC development, differentiation and contractile function.

152 Current Trends in Atherogenesis
