**2. Micro-RNA biology: Biosynthesis and function**

Micro-RNAs (miRNAs) are a large class of evolutionarily conserved, small, endogenous, noncoding RNAs serving as essential post-transcriptional modulators of gene expression [5]. miRNAs regulate biological processes by binding to mRNA 3'-untranslated region (UTR) sequences to attenuate protein synthesis or messenger RNA (mRNA) stability [6]. Acting as genetic switches or fine-tuners, miRNAs are key regulators of diverse biological and patho‐ logical processes, including development, organogenesis, apoptosis, and cell proliferation and differentiation. miRNA dysregulation often results in impaired cellular function and disease progression. It has been estimated that the whole human genome encodes for about 1000 miRNAs which may be located within introns of coding or non-coding genes, within host exons or within intergenic regions [7].

miRNA biogenesis is shown in Figure 1. The transcription process is mediated by the RNApolymerase II that produces long precursor RNAs known as "primary miRNA" (pri-miRNA) with a typical hairpin morphology [8]. A nuclear endonuclease, called DROSHA, then crops the distal stem portion of pri-RNA obtaining shorter chains (pre-miRNA) [9]. Pre-miRNA is transported to the cytoplasm by the nuclear receptor Exportin-5 [10] and processed by DICER, an RNase III, to short double-stranded RNA sequence containing the miRNA and the 'star strand' (miRNA\*). miRNA\* is degraded after stripping the miRNA strand to obtain mature miRNA [11]. Mature miRNA interact with proteins like Argonaute endonuclease (Arg 2), in order to form the RNA-induced silencing complex (RICS), which directs mature miRNA towards the targeted mRNA and bind on their 3' untranslated region (UTR) [6].

A single miRNA may modulate hundreds of miRNAs, and one mRNA has multiple predicted binding sites for miRNAs in their 3'UTR. Furthermore, after cleavage of a target mRNA, miRNAs are not Destroyed; so they may recognise and modulate other mRNAs [5, 12].

cardiovascular diseases. The first study reporting circulating miRNAs in patients with atherosclerosis was published in 2010, demonstrating a reduction of circulating vascular- and inflammation-associated miRNAs (miR-126, miR-17, miR-92a, miR-155) in patients with coronary artery disease (CAD) [14]. In addition, tissue levels of miRNAs were investigated.

Role of MicroRNAs in Cardiovascular Calcification

http://dx.doi.org/10.5772/55326

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Here we summarize and discuss the current knowledge on circulating and tissue miRNAs in

Studies about miRNA expression in calcified vessels are rare. Li *et al.* analyzed the expression of miRNAs in patients with peripheral artery disease (arteriosclerosis obliter‐ ans), characterized by fibrosis of the tunica intima and calcification of the tunica media [15]. miR-21, miR-130a, miR-27b, let-7f, and miR-210 were significantly increased, while miR-221 and miR-222 were decreased in the sclerotic intima, compared to normal vessels [15]. Higher levels of miR-21 and miR-210 were confirmed in a study that compared atherosclerotic with non-atherosclerotic left internal thoracic arteries [16]. In addition, the expression of miR-34a, miR-146a, miR146b-5p, and miR-210 increased more than 4-fold in atherosclerotic arteries. Several predicted targets were downregulated [16]. Another study found a different miRNA pattern using plaque material from the carotid artery, com‐

diseases associated with cardiovascular calcification (Tables 1 and 2).

**3.1. miRNAs in coronary artery disease**

**Figure 1.** Schematic overview of miRNA biogenesis.
