MicroRNA Regulation of Vascular Smooth Muscle Function and Phenotype

Maegdefessel, Lars; Rayner, Katey J.; Leeper, Nicholas J.

doi:10.1161/atvbaha.114.304877

Cited by 45 publications

(37 citation statements)

References 57 publications

(66 reference statements)

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“…Key pathological factors associated with diabetes including high glucose (HG), advanced glycation end products, growth factors and oxidized lipids promote VSMC dysfunction by enhancing inflammatory gene expression, migration and proliferation via activation of multiple signal transduction pathways and downstream transcription factors 5, 7, 11–15 . Recent studies have also identified the role of epigenetic mechanisms and microRNAs (miRNA) in VSMC dysfunction 16–18 . However, much less is known about the role of miRNAs in VSMC dysfunction implicated in diabetic vascular disease.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Vascular Smooth Muscle Cell Dysfunction Under Diabetic Conditions by miR-504

Reddy

Das

Chen

et al. 2016

ATVB

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Objectives Diabetes accelerates pro-atherogenic and pro-inflammatory phenotype of VSMC associated with vascular complications. Evidence shows that microRNAs (miRNAs) play key roles in VSMC functions, but their role under diabetic conditions is unclear. We profiled miRNAs in VSMC from diabetic mice and examined their role in VSMC dysfunction. Approach and Results High throughput small RNA-sequencing identified 135 differentially expressed miRNAs in VSMC from type-2 diabetic db/db mice (db/dbVSMC) versus non-diabetic db/+ mice. Several of these miRNAs were known to regulate VSMC functions. We further focused on miR-504, because it was highly upregulated in db/dbVSMC, and its function in VSMC is unknown. miR-504 and its host gene Fgf13 were significantly increased in db/dbVSMC and in aortas from db/db mice. Bioinformatics analysis predicted that miR-504 targets including signaling adaptor Grb10 and transcription factor Egr2 could regulate growth factor signaling. We experimentally validated Grb10 and Egr2 as novel targets of miR-504. Overexpression of miR-504 in VSMC inhibited contractile genes, and enhanced ERK1/2 activation, proliferation and migration. These effects were blocked by miR-504 inhibitors. Grb10 knockdown mimicked miR-504 functions and increased inflammatory genes. Egr2 knockdown inhibited anti-inflammatory Socs1 and increased pro-inflammatory genes. Furthermore, high-glucose and palmitic acid upregulated miR-504 and inflammatory genes, but downregulated Grb10. Conclusions Diabetes mis-regulates several miRNAs including miR-504 that can promote VSMC dysfunction. Since changes in many of these miRNAs are sustained in diabetic VSMC even after in vitro culture, they may be involved in metabolic memory of vascular complications. Targeting such mechanisms could offer novel therapeutic strategies for diabetic complications.

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Section: Introductionmentioning

confidence: 99%

Regulation of Vascular Smooth Muscle Cell Dysfunction Under Diabetic Conditions by miR-504

Reddy

Das

Chen

et al. 2016

ATVB

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“…MicroRNAs regulate SMC gene expression and differentiation by inhibiting translation or degrading mRNA [148]. miR-145/143 are derived from the same primary miR and are simultaneously expressed to promote VSMC differentiation [149].…”

Section: Micrornasmentioning

confidence: 99%

Development of Mural Cells: From In Vivo Understanding to In Vitro Recapitulation

Shen¹,

McCloskey

2017

Stem Cells and Development

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Mural cells are indispensable for the development and maintenance of healthy mature vasculature, valuable for vascular therapies and as developmental models. However, their functional plasticity, developmental diversity, and multitude of differentiation pathways complicate in vitro generation. Fortunately, there is a vast pool of untapped knowledge from in vivo studies that can guide in vitro engineering. This review highlights the in vivo genesis of mural cells from progenitor populations to recruitment pathways to maturation and identity with an emphasis on how this knowledge is applicable to in vitro models of stem cell differentiation.

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“…First, a single miRNA can regulate several hundred target genes (including targets in the same or complimentary cellular pathways) making miRNAs potentially very powerful disease modifiers [22]. Second, several lines of evidence demonstrate that miRNAs are essential regulators of VSMC development, differentiation, and contractile function offering a rich repertoire of disease-modifying therapeutics [23]. Finally, RNA therapeutics benefit from a great deal of prior translational research (e.g.…”

Section: Mirna Biogenesis and Functionmentioning

confidence: 99%

Role of noncoding RNA in vascular remodelling

Lin

Bradshaw

Baker

2016

Current Opinion in Lipidology

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Purpose of review: Non-coding RNA (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (LncRNAs), are becoming fundamentally important in the pathophysiology relating to injury-induced vascular remodelling. We highlight recent studies that demonstrate the involvement of ncRNAs in vein graft disease, in in-stent restenosis (ISR) and in pulmonary arterial hypertension (PAH), with a particular focus on endothelial cell (EC) and vascular smooth muscle cell (VSMC) function. We also briefly discuss the emerging role of exosomal-derived ncRNAs and how this mechanism impacts on vascular function.

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MicroRNA Regulation of Vascular Smooth Muscle Function and Phenotype

Cited by 45 publications

References 57 publications

Regulation of Vascular Smooth Muscle Cell Dysfunction Under Diabetic Conditions by miR-504

Regulation of Vascular Smooth Muscle Cell Dysfunction Under Diabetic Conditions by miR-504

Development of Mural Cells: From In Vivo Understanding to In Vitro Recapitulation

Role of noncoding RNA in vascular remodelling

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