In addition, remodeling and hypertrophy of VSMCs may be involved in the progression of essential hypertension. The mechanisms of VSMC phenotypic modulation remain elusive despite intense investigation. However, several transcription factors, including serum response factor, myocardin, myocardin related transcription factors and members of the Kru�� ppel-like zinc finger family have been suggested to act as molecular switches regulating VSMC differentiation. During the last decade, microRNAs, which are short noncoding RNAs have been suggested to regulate mRNA expression NSC-718781 levels and translational efficiency and play a fundamental role in a number of human disease states, including vascular disease. Specific miRNAs have been shown to regulate VSMC phenotypic modulation and/or control VSMC fate and differentiation. miR-21 and miR-221 were initially found to play a role in SMC proliferation and differentiation and more recently, miR-145 was shown to be specifically expressed in SMCs and play an important role in SMC differentiation. Studies on miR-143/145 KO mice later revealed that these miRNAs are important but not essential for VSMC development in vivo. miRNAs are produced from immature pre-miRNAs, which are processed by the two RNase III endonucleases, Drosha and Dicer, and are then incorporated into the RNA-induced silencing complex . Depending on the complementarity of the miRNA with the 3��-untranslated region of the target mRNA, the RISC complex will mediate either translational repression/ activation or degradation of the target mRNA. Since Dicer is required for processing of almost all mature miRNAs, mutation or disruption of Dicer has been widely used as an approach to investigate the biological significance of miRNAs in Gefitinib various cell types including cardiomyocytes, endothelial cells, fibroblasts and immune cells 24�C26]. Our group recently reported that conditional loss of Dicer in VSMCs during embryonic development results in embryonic lethality associated with extensive internal hemorrhage as well as dilated and thin walled blood vessels caused by a reduction in cellular proliferation. In addition, arteries from SM-Dicer KO embryos exhibited impaired contractility due to a loss of contractile differentiation of VSMCs. In isolated Dicer KO VSMCs, loss of contractile differentiation was rescued by miR-145 mimic, possibly via increased actin polymerization. Although miR-145 can rescue several defects in cultured SMCs, the absence of a lethal phenotype of miR-145 KO mice suggests that other miRNAs or combinations of miRNAs are important for SMC development and function. Since deletion of Dicer during prenatal development is embryonic lethal it is not possible to investigate the importance of miRNAs in VSMC function and blood pressure regulation in adult mice using this model.