Endothelial MicroRNA Tells Smooth Muscle Cells to Proliferate

Boon, Reinier A.

doi:10.1161/circresaha.113.301636

Cited by 6 publications

(3 citation statements)

References 17 publications

(22 reference statements)

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“…(2) The elective percutaneous intervention (PCI) group comprised patients who had PCI performed within 2 weeks (n ¼ 15). (3) The emergency PCI group comprised patients who had PCI performed within 12 hours (n ¼ 20) (Supplementary Table 1). The PCI groups included patients who exclusively had effort-related angina with a positive exercise stress test and at least one coronary stenosis was detected at angiography with > 70% reduction of the lumen diameter.…”

Section: Patientsmentioning

confidence: 99%

“…2 Endothelial release of miR126 bound to the protein argonaute 2 modulates smooth muscle gene expression and promotes a proatherogenic phenotype in smooth muscle cells. 3 mRNA regulatory Ago2•miRNA-223 complexes can be transported by activated platelets to endothelial cells. 4 Extracellular vesicles (EVs) are nanovesicles of endocytic origin that are released from most cell types.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of capillary tubules and lipid formation in vascular endothelial cells and macrophages via extracellular vesicle-mediated microRNA-4306 transfer

et al. 2018

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Objective This study aimed to examine regulation of capillary tubules and lipid formation in vascular endothelial cells and macrophages via extracellular vesicle-mediated microRNA (miRNA)-4306 transfer Methods Whole blood samples (12 mL) were collected from 53 patients, and miR-4306 levels in extracellular vesicles (EVs) were analyzed by reverse transcription-polymerase chain reaction. Human coronary artery vascular endothelial cells (HCAECs) and human monocyte-derived macrophages (HMDMs) were transfected with a scrambled oligonucleotide, an miR-4306 mimic, or an anti-miR-4306 inhibitor. The direct effect of miR-4306 on the target gene was analyzed by a dual-luciferase reporter assay. Results EV-contained miR-4306 released from HMDMs was significantly upregulated in coronary artery disease. Oxidized low-density lipoprotein (ox-LDL)-stimulated HMDM-derived EVs inhibited proliferation, migration, and angiogenesis abilities of HCAECs in vitro. However, ox-LDL-stimulated HCAEC-derived EVs enhanced lipid formation of HMDMs. The possible mechanism of these findings was partly due to EV-mediated miR-4306 upregulation of the Akt/nuclear factor kappa B signaling pathway. Conclusions Paracrine cellular crosstalk between HCAECs and HMDMs probably supports the pro-atherosclerotic effects of EVs under ox-LDL stress.

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Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulation of capillary tubules and lipid formation in vascular endothelial cells and macrophages via extracellular vesicle-mediated microRNA-4306 transfer

et al. 2018

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“…PDGF stimulation could inhibit the expression of miR-221, leading to down-regulation of the targets p27 (Kip1) and c-Kit. Down-regulation of p27 (Kip1) What's more, the damaged endothelial cells also could secret miRNAs to promote the SMC phenomenon switching via vesicles mediated intercellular communication [33,34]. Vesicle-mediated miRNAs has been proved in atherosclerosis while the research is very few in PAH, and it will become a new research hotspot.…”

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confidence: 99%

MicroRNAs and Smooth Muscle Cells Phenotypic Switching in PAH

Wu¹

2014

J Pulm Respir Med

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Smooth muscle cells undergo a switching from contractile phenotype to synthetic phenotype in pulmonary hypertension characterized by excessive proliferation and migration of smooth muscle cells. MicroRNAs are small noncoding RNAs that can negatively regulate gene expression by directly binding with the 3'-UTR of mRNA. Numerous microRNAs have been reported to modulate the smooth muscle cells phenotypic switching and been urged to become possible therapeutic targets for pulmonary hypertension. This review will focus on the roles of microRNAs in regulating smooth muscle cellular phenotypic switching in PAH. MicroRNAs (miRNAs) are a novel class of endogenous, small and non-coding RNAs that function in transcriptional and posttranscriptional regulation of gene expression by directly binding with the 3'-UTR of mRNA [6][7][8]. miRNAs can directly regulate about 30% of the genes in a cell [9], therefore it is not surprising that miRNAs are involved in the regulation of almost all major cellular function, including developmental timing, cell death, cell proliferation [10,11], fat storage [12], haematopoiesis [13][14][15][16][17][18] and patterning of the nervous system [19][20][21][22]. Recent studies have revealed that many non-coding miRNAs can be as novel phenotypic markers and modulators of Vascular Smooth Muscle Cells (VSMCs). These findings display extensive implications for the diagnosis and therapy of a variety of proliferative vascular diseases [23], including PAH. The review will focus on the roles of microRNAs in regulating smooth muscle cellular phenotypic switching in pulmonary hypertension.There are two classic pulmonary hypertension animal models apart induced by monocrotaline (MCT) and hypoxia [24]. In pulmonary hypertension induced by MCT, it usually occurs that endothelial cells damage accompanied with the increasing release of growth factors. PDGF is one of the most common growth factors in PAH and released primarily by vascular endothelial cells and platelets at the sites of vascular injury [25]. Indeed, an increased expression of signaling proteins in the PDGF pathway has been demonstrated in several cardiovascular disorders [26]. Activation of PDGF inhibits smooth muscle cell (SMC)-specific gene expression (SM22α, SM α-actin and calponin) and increases the rate of proliferation and migration, leading to dedifferentiation of VSMCs. Many miRNAs have been demonstrated to play important roles in the stimulation of PDGF with indistinct mechanisms.MiR-15b is shown to be induced by PDGF in pulmonary artery smooth muscle cells and it is critical for the repression of SMC-specific contractile genes [27]. MiR-638 is abundantly expressed in SMCs and markedly down-regulated in the PDGF stimulation. In differentiation medium, miR-638 expression is significantly up-regulated to inhibit SMC proliferation by targeting the orphan nuclear receptor NOR1 [25]. MiR-24 also functions in the process and directly down-regulates Tribbles like protein-3 (Trb3) expression which results in decreased Smad protein levels...

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Decoding microRNA drivers in atherosclerosis

2022

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An estimated 97% of the human genome consists of non-protein-coding sequences. As our understanding of genome regulation improves, this has led to the characterization of a diverse array of non-coding RNAs (ncRNA). Among these, micro-RNAs (miRNAs) belong to the short ncRNA class (22-25 nucleotides in length), with approximately 2,500 miRNA genes encoded within the human genome. From a therapeutic perspective, there is interest in exploiting miRNA as biomarkers of disease progression and response to treatments, as well as miRNA mimics/repressors as novel medicines. miRNA have emerged as an important class of RNA master regulators with important roles identified in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Atherosclerosis is characterized by a chronic inflammatory build-up, driven largely by low-density lipoprotein cholesterol (LDL-C) accumulation within the artery wall and vascular injury, including endothelial dysfunction, leukocyte recruitment and vascular remodelling. Conventional therapy focuses on lifestyle interventions, blood pressure-lowering medications, high-intensity statin therapy and antiplatelet agents. However, a significant proportion of patients remain at increased risk of cardiovascular disease (CVD). This continued cardiovascular risk is referred to as residual risk. Hence, a new drug class targeting atherosclerosis could synergise with existing therapies to optimise outcomes. Here we review our current understanding of the role of ncRNA, with a focus on miRNA, in the development and progression of atherosclerosis, highlighting novel biological mechanisms and therapeutic avenues.

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Endothelial MicroRNA Tells Smooth Muscle Cells to Proliferate

Cited by 6 publications

References 17 publications

Regulation of capillary tubules and lipid formation in vascular endothelial cells and macrophages via extracellular vesicle-mediated microRNA-4306 transfer

Regulation of capillary tubules and lipid formation in vascular endothelial cells and macrophages via extracellular vesicle-mediated microRNA-4306 transfer

MicroRNAs and Smooth Muscle Cells Phenotypic Switching in PAH

Decoding microRNA drivers in atherosclerosis

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