MicroRNA-133 Controls Vascular Smooth Muscle Cell Phenotypic Switch In Vitro and Vascular Remodeling In Vivo

Abstract

Key Words: vascular smooth muscle cells Ⅲ microRNA Ⅲ miR-133 Ⅲ smooth muscle differentiation Ⅲ vascular remodeling V ascular smooth muscle cells (VSMCs) within adult blood vessels proliferate at a very low rate, exhibit very low synthetic activity, and express a unique repertoire of contractile proteins, ion channels, and signaling molecules. 1 Unlike skeletal muscle and cardiac muscle, which consist of terminally differentiated cells, adult VSMCs retain remarkable plasticity and can undergo rather profound and reversible changes in phenotype and growth properties in response to changes in local environmental cues. Salient examples of VSMC plasticity can be seen in response to vascular injury when VSMCs dramatically increase their proliferation, migration, and synthetic capacity, playing a critical role in vascular repair. 1,2 A detrimental consequence of the high degree of plasticity exhibited by adult VSMCs is that it can lead to an adverse phenotypic switch and acquisition of characteristics that can contribute to development or progression of vascular disease in humans, including atherosclerosis, restenosis, cancer, and hypertension. [1][2][3] VSMC phenotypic modulation is characterized by significant changes in gene expression patterns, matrix and cytokine production, contractility, and growth state, ultimately leading to their switch from a synthetic to a proliferative phenotype.Original received January 3, 2011; revision received August 8, 2011; accepted August 9, 2011. In July 2011, the average time from submission to first decision for all original research papers submitted to Circulation Research was 13.5 days.From Thus, understanding the regulatory mechanisms underlying the VSMC phenotypic switch is of paramount importance. [1][2][3] One of the key breakthroughs for the study of gene expression regulation has recently been the discovery of microRNAs (miRNAs or miRs) and their role in gene silencing through mRNA degradation or translational inhibition. 4,5 Increasing evidence indicates that miRNAs regulate key genetic programs in cardiovascular biology, physiology, and disease. 4,5 In particular, miR-21, -143, -145, -221, -222 have all been implicated to play a role in VSMC function and phenotypic plasticity. 6 -11 More recently, 2 articles demonstrated that miR-1 is induced by myocardin overexpression in human SMCs, contributing to myocardin-dependent reduction of human SMC growth in vitro. 12,13 miR-133a-1/miR-1-2 and miR133a-2/miR-1-1 are 2 bicistronic miRNA clusters reported to be specifically expressed in cardiac and skeletal muscle. 4,5 A third bicistronic miRNA cluster, comprising miR-206 and miR-133b, is expressed specifically in skeletal muscle but not in the heart. 4,5 miR-1 (miR-1-1/miR-1-2) and miR-133 (miR133a-1/miR-133a-2) play essential roles in cardiac and skeletal muscle development, physiology, and disease 4,5 ; however, their functions in VSMCs and vascular disease are largely unknown. Thus, the aim of the present study was to evaluate the role, if any, of miR-1 and miR-133 in V...

Key Role of MicroRNA in the Regulation of Granulocyte Macrophage Colony-stimulating Factor Expression in Murine Alveolar Epithelial Cells during Oxidative Stress

“…38 and 39). It is enriched in cardiac myocytes (40) and vascular smooth muscle cells (41). In each instance, miR133 appears to play an important role suppressing cell growth (42,43) and expression of extracellular matrix constituents (44).…”

miRNAs and lncRNAs in vascular injury and remodeling

“…Similarly, over-expression of miR-21 increases proliferation and reduces apoptosis of VSMC [41]. On the other hand, miR-133 reduces proliferation and migration of VSMC through repressing transcription factor Sp-1 [42], while miR-143/145 inhibits proliferation and increases differentiation of VSMC, leading to repressing neointima formation following carotid artery balloon injury by directly suppressing transcription factor KLF4/5 [37]. Further knockout studies have demonstrated that loss function of the miR-143/145 significantly compromises the contractile phenotype of VSMC [43].…”

Circulation Research Thematic Synopsis

“…Brain-targeted ACE2 overexpression attenuated the development of neurogenic hypertension (Ang II infusion: 600 ng/kg per minute for 14 days) and the associated reduction of both SBRS and parasympathetic tone. This prevention of hypertension by ACE2 overexpression was reversed by blockade of the Ang-(1-7) receptor (d-Ala7-Ang- [1][2][3][4][5][6][7]; 600 ng/ kg per minute). Brain angiotensin II type 2 (AT2)/AT1 and Mas/AT1 receptor ratios were significantly increased in SA mice.…”

“…Furthermore, vascular microRNA and non-coding RNAs have emerged as major regulators of vessel wall homeostasis and pathologies. [5][6][7][8][9][10][11][12][13] These molecular networks are currently being investigated as specific targets for interventions to prevent and assuage vascular diseases. Since identification of the first specific angiogenic molecule by Folkman and colleagues in 1971, a large number of proangiogenic factors have been identified and characterized.…”