miRNA-34a reduces neointima formation through inhibiting smooth muscle cell proliferation and migration

Chen, Qishan; Yang, Feng; Guo, Meiqun; Wen, Guangwu; Zhang, Cheng; Luong, Le Anh; Zhu, Jianhua; Xiao, Qingzhong; Zhang, Li

doi:10.1016/j.yjmcc.2015.10.017

Cited by 71 publications

(93 citation statements)

References 82 publications

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“…Real‐time quantitative polymerase chain reaction was performed as previously described 17, 18, 19, 27, 28, 29, 30, 31. Briefly, total RNA was extracted from murine aortas or cells using Trizol reagent (Sigma) according to the manufacturer's instructions and subjected to DNase I (Sigma) digestion to remove potential DNA contamination.…”

Section: Methodsmentioning

confidence: 99%

Genetic and Pharmacologic Inhibition of the Neutrophil Elastase Inhibits Experimental Atherosclerosis

Wen

Chen

et al. 2018

JAHA

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BackgroundTo investigate whether neutrophil elastase (NE) plays a causal role in atherosclerosis, and the molecular mechanisms involved.Methods and Results NE genetic–deficient mice (Apolipoprotein E−/−/NE −/− mice), bone marrow transplantation, and a specific NE inhibitor (GW311616A) were employed in this study to establish the causal role of NE in atherosclerosis. Aortic expression of NE mRNA and plasma NE activity was significantly increased in high‐fat diet (HFD)–fed wild‐type (WT) (Apolipoprotein E−/−) mice but, as expected, not in NE‐deficient mice. Selective NE knockout markedly reduced HFD‐induced atherosclerosis and significantly increased indicators of atherosclerotic plaque stability. While plasma lipid profiles were not affected by NE deficiency, decreased levels of circulating proinflammatory cytokines and inflammatory monocytes (Ly6Chi/CD11b+) were observed in NE‐deficient mice fed with an HFD for 12 weeks as compared with WT. Bone marrow reconstitution of WT mice with NE −/− bone marrow cells significantly reduced HFD‐induced atherosclerosis, while bone marrow reconstitution of NE −/− mice with WT bone marrow cells restored the pathological features of atherosclerotic plaques induced by HFD in NE‐deficient mice. In line with these findings, pharmacological inhibition of NE in WT mice through oral administration of NE inhibitor GW311616A also significantly reduced atherosclerosis. Mechanistically, we demonstrated that NE promotes foam cell formation by increasing ATP‐binding cassette transporter ABCA1 protein degradation and inhibiting macrophage cholesterol efflux.ConclusionsWe outlined a pathogenic role for NE in foam cell formation and atherosclerosis development. Consequently, inhibition of NE may represent a potential therapeutic approach to treating cardiovascular disease.

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Section: Methodsmentioning

confidence: 99%

Genetic and Pharmacologic Inhibition of the Neutrophil Elastase Inhibits Experimental Atherosclerosis

Wen

Chen

et al. 2018

JAHA

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“…The migration of VSMCs was evaluated using a scratch wound healing assay and transwell migration assays as previously described [10]. …”

Section: Methodsmentioning

confidence: 99%

MiR-29b Downregulation Induces Phenotypic Modulation of Vascular Smooth Muscle Cells: Implication for Intracranial Aneurysm Formation and Progression to Rupture

Zhao

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Our previous microarray results identified numerous microRNAs (miRNAs), including miR-29b, that were differentially expressed in the serum of intracranial aneurysm (IA) patients. The current study aimed to investigate whether miR-29b downregulation in IA could promote the phenotypic modulation of vascular smooth muscle cells (VSMCs) involved in the pathogenesis of aneurysm by activating ATG14-mediated autophagy. Methods: First, the levels of miR-29b and autophagy related genes (ATGs) between IA patients and normal subjects were compared. Next, we modified the level of miR-29b via lentivirus particles in the VSMCs and examined the effects of miR-29b on proliferation, migration, and phenotypic modulation of VSMCs from a contractile phenotype to a synthetic phenotype, as well as the levels of autophagy. Finally, the binding of miR-29b to the 3’UTR of ATG14 mRNA and its effects on ATG14 expression were analysed by a luciferase reporter assay and Western blot, respectively. Results: The level of miR-29b was decreased, and autophagy markers were increased in the IA patients compared to that of the normal subjects. Knockdown of miR-29b significantly promoted VSMCs proliferation and migration and, more importantly, induced the phenotypic modulation associated with autophagy activation, whereas miR-29b overexpression showed the opposite effects. The luciferase reporter assay demonstrated that ATG14 was a functional target gene of miR-29b. Notably, knockdown of ATG14 by siRNA apparently abrogated miR-29b inhibition-mediated phenotypic modulation. Conclusion: Downregulation of miR-29b induced VSMCs phenotypic modulation by directly activating ATG14-mediated autophagy, which is associated with the formation, growth and rupture of IAs.

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“…Roles for endothelial Notch1 have also been described in adult cardiovascular disease, including valve calcification (43,44 Figure 2). Several publications have demonstrated a less predominant role for Notch1 in SMC in the vasculature, including neointimal repair after injury (46)(47)(48). Therefore, we sought to determine if loss of SMC-specific Notch1 was the cause of the exacerbated phenotype observed in the Notch1…”

Section: ;Fbn1mentioning

confidence: 97%

Notch1 haploinsufficiency causes ascending aortic aneurysms in mice

Koenig¹,

LaHaye²,

Feller³

et al. 2017

JCI Insight

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miRNA-34a reduces neointima formation through inhibiting smooth muscle cell proliferation and migration

Cited by 71 publications

References 82 publications

Genetic and Pharmacologic Inhibition of the Neutrophil Elastase Inhibits Experimental Atherosclerosis

Genetic and Pharmacologic Inhibition of the Neutrophil Elastase Inhibits Experimental Atherosclerosis

MiR-29b Downregulation Induces Phenotypic Modulation of Vascular Smooth Muscle Cells: Implication for Intracranial Aneurysm Formation and Progression to Rupture

Notch1 haploinsufficiency causes ascending aortic aneurysms in mice

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