**2. MicroRNAs**

MicroRNAs (miRNAs or miRs) are small noncoding RNA molecules approximately 18–25 nucleotides in length that participate in controlling gene expression at the posttranscriptional level [13]. MicroRNAs directly bind to 3 untranslated regions (3UTR) of target mRNAs, leading to translational inhibition and/or mRNA degradation [9]. One miRNA can suppress multiple target protein-coding mRNAs, which also means that a single protein can be regulated by numerous miRNAs [14]. Interestingly, about two-thirds of the coding-mRNA genes are regulated by miRNAs [15]. Since the first discovery of miRNAs in *Caenorhabditis elegans* in 1993, more than 1800 miRNAs in human have been identified and recorded in miRBase 21 (www.mirbase.org) [16].

The biogenesis of miRNAs are initiated by transcription from their genes by RNA polymerase II, which produces primary miRNAs (pri-miRNAs) with hundreds to thousands of nucleotides and single or multiple stem-loop-like structures [17]. After transcription, the pri-miRNAs are cleaved at ~70-nucleotide hairpin-shaped precursor miRNA (pre-miRNA) by RNase-III endonuclease (Drosha) and DiGeorge syndrome Critical Region 8 protein (DGCR8) complex [18]. The pre-miRNAs are transferred from nuclear to cytoplasm through the nuclear export protein exportin-5 [19]. In the cytoplasm, the pre-miRNAs are processed to produce mature miRNA duplex mediated by RNase-III endonuclease, Dicer: the passenger strand and the guide strand (~22 nucleotides long) [20]. The guide strand is loaded to RNA-induced silencing complex (RISC), and the passenger strand is degraded [21]. The miRNA–RISC complex recognizes and binds the miRNA based on the complementary match between the miRNA seed sequence (2–8 nucleotides in the 5' end) and the 3 UTR of the target mRNA, and this results in translational suppression and/or mRNA degradation (Figure 1) [22, 23].

**Figure 1.** The biogenesis of miRNAs.

remodeling, the EC dysfunction, synthetic or contractile phenotypic change of VSMCs, and the infiltration of monocytes and macrophages promote vascular diseases including athero‐ sclerosis [3, 4]. Therefore, modulation of VSMC phenotype, maintenance of ECs, and regula‐ tion of inflammation in the vessel wall are important in arterial function and homeostasis.

Recent findings have been demonstrated that microRNAs (miRNAs) are involved in regulat‐ ing gene expressions at posttranscriptional level and disease pathogenesis [5, 6]. Importantly, altered specific set of miRNAs is closely related to cell fate determination, tissue function, and homeostasis [7, 8], indicating that miRNAs plays key roles in the gene expressions and the regulation of cellular functions [9]. Consequently, the change of miRNA expressions can lead to VSMC phenotype switch, EC dysfunction, and the inflammatory response and lipid

In this chapter, we summarize the vascular remodeling-related miRNAs and the function of these miRNAs in vascular biology, and suggest novel therapeutic strategies for the treatment and/or prevention of vascular diseases via controlling the expressions of miRNA regulation.

MicroRNAs (miRNAs or miRs) are small noncoding RNA molecules approximately 18–25 nucleotides in length that participate in controlling gene expression at the posttranscriptional level [13]. MicroRNAs directly bind to 3 untranslated regions (3UTR) of target mRNAs, leading to translational inhibition and/or mRNA degradation [9]. One miRNA can suppress multiple target protein-coding mRNAs, which also means that a single protein can be regulated by numerous miRNAs [14]. Interestingly, about two-thirds of the coding-mRNA genes are regulated by miRNAs [15]. Since the first discovery of miRNAs in *Caenorhabditis elegans* in 1993, more than 1800 miRNAs in human have been identified and recorded in miRBase 21

The biogenesis of miRNAs are initiated by transcription from their genes by RNA polymerase II, which produces primary miRNAs (pri-miRNAs) with hundreds to thousands of nucleotides and single or multiple stem-loop-like structures [17]. After transcription, the pri-miRNAs are cleaved at ~70-nucleotide hairpin-shaped precursor miRNA (pre-miRNA) by RNase-III endonuclease (Drosha) and DiGeorge syndrome Critical Region 8 protein (DGCR8) complex [18]. The pre-miRNAs are transferred from nuclear to cytoplasm through the nuclear export protein exportin-5 [19]. In the cytoplasm, the pre-miRNAs are processed to produce mature miRNA duplex mediated by RNase-III endonuclease, Dicer: the passenger strand and the guide strand (~22 nucleotides long) [20]. The guide strand is loaded to RNA-induced silencing complex (RISC), and the passenger strand is degraded [21]. The miRNA–RISC complex recognizes and binds the miRNA based on the complementary match between the miRNA seed sequence (2–8 nucleotides in the 5' end) and the 3 UTR of the target mRNA, and this

results in translational suppression and/or mRNA degradation (Figure 1) [22, 23].

accumulation of macrophage in vascular pathophysiology [10–12].

**2. MicroRNAs**

56 Muscle Cell and Tissue

(www.mirbase.org) [16].

Increasing evidence suggests that miRNAs play important roles in a wide range of biological functions and processes, including but not limited to, development, growth, pathophysiology, regeneration, inflammation, stem cell fate regulation, and aging [24–29]. Because the changes of miRNA expression profiles are related to various human diseases, such as cardiovascular diseases, cancer, neuropathy, infection, and metabolic disorders [9, 30–34], the modulation of miRNA expressions consider as a novel therapeutic target and may inspire a new strategy for treatment of these diseases [35–37].
