scholarly journals Hsa_circ_0054633 regulates PDGF-BB-induced proliferation, migration and oxidative stress of vascular smooth muscle cells through miR-107/TXNIP axis

2021 ◽  
Author(s):  
Xiaochun Lei ◽  
Yi Ding ◽  
Ye Tian ◽  
Peng Ding
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Cell Counting ◽  
Nuclear Antigen ◽  
Luciferase Reporter ◽  
Human Artery ◽  
Interacting Protein ◽  
Vsmc Proliferation ◽  
And Migration

IntroductionHsa_circ_0054633 has been found to be elevated in the blood of coronary artery disease (CAD) patients. However, the molecular mechanism and the role of hsa_circ_0054633 in the pathogenesis of CAD have not been reported in detail.Material and methodsThe expression of hsa_circ_0054633, microRNA (miR)-107 and thioredoxin-interacting protein (TXNIP) mRNA was measured using quantitative real-time polymerase chain reaction. Human artery vascular smooth muscle cell (HA-VSMC) proliferation, cell cycle, and migration were detected by cell counting kit-8 assay, flow cytometry and transwell assay, respectively. The generation of reactive oxygen species (ROS) was analyzed by dichlorofluorescein diacetate (DCFH-DA) assay. Western blot was utilized to determine the levels of proliferating cell nuclear antigen (PCNA), cyclin D1, matrix metallopeptidase 9 (MMP-9), Mn-superoxide dismutase (SOD2) and TXNIP protein. The interaction between miR-107 and hsa_circ_0054633 or TXNIP was confirmed by dual-luciferase reporter, RNA immunoprecipitation assay or pull-down assay.ResultsHsa_circ_0054633 was elevated in the plasma of CAD patients, and might be a potential blood biomarker for CAD prediction. Hsa_circ_0054633 silencing reversed PDGF-BB-induced promotion on HA-VSMC proliferation, cell cycle, migration and ROS production. MiR-107 directly interacted with hsa_circ_0054633 and TXNIP, and hsa_circ_0054633 regulated TXNIP expression by sponging miR-107. Besides, rescue assay indicated that the action of hsa_circ_0054633 silencing on PDGF-BB-treated HA-VSMCs could be attenuated by miR-107 inhibition or TXNIP overexpression, respectively.ConclusionsHsa_circ_0054633 knockdown protected HA-VSMCs against PDGF-BB-induced dysfunction through regulating miR-107/TXNIP axis, suggesting a potential therapeutic target for coronary atherosclerosis.

scholarly journals Aldose Reductase Regulates Vascular Smooth Muscle Cell Proliferation by Modulating G1/S Phase Transition of Cell Cycle

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2140-2150 ◽  
Author(s):  
Ravinder Tammali ◽  
Ashish Saxena ◽  
Satish K. Srivastava ◽  
Kota V. Ramana
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Aldose Reductase ◽  
S Phase ◽  
Nuclear Antigen ◽  
Proliferative Cell Nuclear Antigen ◽  
Vsmc Proliferation ◽  
Tnf Α ◽  
Proliferative Cell

Abnormal proliferation of vascular smooth muscle cells (VSMC) is a key feature of development of cardiovascular complications, atherosclerosis, and restenosis. Patients with diabetes have higher risk for restenosis after coronary angioplasty than nondiabetic patients due to hyperglycemia-induced release of cytokines such as TNF-α. However, the molecular mechanisms regulating VSMC proliferation remain unclear. Herein, we report that inhibition of the polyol pathway enzyme aldose reductase (AR) prevents high glucose (HG)- and/or TNF-α-induced VSMC proliferation by accumulating cells at the G1 phase of the cell cycle. Treatment of VSMC with AR inhibitor sorbinil prevented HG- as well as TNF-α-induced phosphorylation of retinoblastoma protein and activation of E2F-1. Inhibition of AR also prevented HG- and TNF-α-induced phosphorylation of cyclin-dependent kinase (cdk)-2 and expression of G1/S transition regulatory proteins such as cyclin D1, cyclin E, cdk-4, c-myc, and proliferative cell nuclear antigen. More importantly, inhibition of AR prevented the increased expression of E2F-1 and proliferative cell nuclear antigen in diabetic rat aorta. Treatment of VSMC with the most abundant and toxic lipid aldehyde 4-hydroxy-trans-2-nonenal (HNE) or its glutathione conjugate [glutathionyl (GS)-HNE] or AR-catalyzed product of GS-HNE, GS-1,4-dihydroxynonane, resulted in increased E2F-1 expression. Inhibition of AR prevented HNE- or GS-HNE-induced but not GS-1,4-dihydroxynonane-induced up-regulation of E2F-1. Collectively, these results show that AR could regulate HG- and TNF-α-induced VSMC proliferation by altering the activation of G1/S-phase proteins such as E2F-1, cdks, and cyclins. Thus, inhibition of AR may be a useful therapeutic approach in preventing vascular complications.

scholarly journals LncRNA SNHG12 promotes proliferation and migration of vascular smooth muscle cells via targeting miR-766-5p/ EIF5A

2020 ◽  
Author(s):  
wen liu ◽  
jianhuan che ◽  
Yan Gu ◽  
ling song ◽  
yingying Jiao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Translation Initiation Factor ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Although lncRNAs have reported to serve as potential biomarkers of atherosclerosis (AS), the role of lncRNA SNHG12 in AS are still unknown. Methods In present study, we investigated the regulatory effects of SNHG12 on human vascular smooth muscle cells (hVSMCs). RT-qPCR were employed to determine the expressions of SNHG12, miR-766-5p and eukaryotic translation initiation factor 5A (EIF5A). Cell viability was estimated via the Cell Counting Kit-8 assay. Wound healing and Transwell invasion assays were used for evaluation of hVSMCs migratory capacity. To further investigate the regulatory mechanisms, binding sites between SNHG12 and miR-766-5p, EIF5A and miR-766-5p were speculated via starBase V2.0, and validated using luciferase reporter gene assay. Results It was identified that SNHG12 was up-regulated in oxidized low-density lipoprotein (ox-LDL)-insulted hVSMCs. Silencing SNHG12 inhibited ox-LDL-induced proliferation and migration of hVSMCs. Moreover, we found that SNHG12 acted as a sponge of miR-766-5p, and miR-766-5p also interacted with EIF5A. EIF5A plasmids promoted the proliferation and migratory capacities of hVSMCs, however, shRNA-SNHG12 counteracted the facilitation of EIF5A plasmids on biological behaviors of hVSMCs. Conclusions These findings of this study demonstrated that SNHG12 facilitated the migration and invasion of hVSMCs via targeting miR-766-5p/EIF5A axis.

scholarly journals Salusin-α Inhibits Proliferation and Migration of Vascular Smooth Muscle Cell via Akt/mTOR Signaling

2018 ◽  
Vol 50 (5) ◽  
pp. 1740-1753 ◽  
Author(s):  
Shoucui Gao ◽  
Liran Xu ◽  
Yali Zhang ◽  
Qingqing Yu ◽  
Jiayan Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Atherosclerotic Lesion ◽  
Cell Counting ◽  
Matrix Metalloproteinase 2 ◽  
Aortic Lesion ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: The proliferation and migration of vascular smooth muscle cells (VSMCs) are key steps in the progression of atherosclerosis. The aim of the present study was to investigate the potential roles of salusin-α in the functions of VSMCs during the development of atherosclerosis. Methods: In vivo, the effects of salusin-α on atherogenesis were examined in rabbits fed a cholesterol diet. The aortas were en face stained with Sudan IV to evaluate the gross atherosclerotic lesion size. The cellular components of atherosclerotic plaques were analyzed by immunohistochemical methods. In vitro, Cell Counting Kit-8 and wound-healing assays were used to assess the effects of salusin-α on VSMC proliferation and migration. In addition, western blotting was used to evaluate the total and phosphorylated levels of Akt (also known as protein kinase B) and mammalian target of rapamycin (mTOR) in VSMCs. Results: Salusin-α infusion significantly reduced the aortic lesion areas of atherosclerosis, with a 39% reduction in the aortic arch, a 71% reduction in the thoracic aorta, and a 71% reduction in the abdominal aorta; plasma lipid levels were unaffected. Immunohistochemical staining showed that salusin-α decreased both macrophage- and VSMC-positively stained areas in atherosclerotic lesions by 54% and 69%, cell proliferative activity in the intima and media of arteriosclerotic lesions, and matrix metalloproteinase 2 (MMP-2) and MMP-9 expression in plaques. Studies using cultured VSMCs showed that salusin-α decreased VSMC migration and proliferation via reduced phosphorylation of Akt and mTOR. Conclusion: Our data indicate that salusin-α suppresses the development of atherosclerosis by inhibiting VSMC proliferation and migration through the Akt/mTOR pathway.

Cinnamon and its Components Suppress Vascular Smooth Muscle Cell Proliferation by Up-Regulating Cyclin-Dependent Kinase Inhibitors

2015 ◽  
Vol 43 (04) ◽  
pp. 621-636 ◽  
Author(s):  
Hyeeun Kwon ◽  
Jung-Jin Lee ◽  
Ji-Hye Lee ◽  
Won-Kyung Cho ◽  
Min Jung Gu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Signal Transduction ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Regulatory Proteins ◽  
Nuclear Antigen ◽  
Active Components ◽  
Vsmc Proliferation ◽  
Cinnamon Extract ◽  
Early Signal

Cinnamomum cassia bark has been used in traditional herbal medicine to treat a variety of cardiovascular diseases. However, the antiproliferative effect of cinnamon extract on vascular smooth muscle cells (VSMCs) and the corresponding restenosis has not been explored. Hence, after examining the effect of cinnamon extract on VSMC proliferation, we investigated the possible involvement of signal transduction pathways associated with early signal and cell cycle analysis, including regulatory proteins. Besides, to identify the active components, we investigated the components of cinnamon extract on VSMC proliferation. Cinnamon extract inhibited platelet-derived growth factor (PDGF)-BB-induced VSMC proliferation and suppressed the PDGF-stimulated early signal transduction. In addition, cinnamon extract arrested the cell cycle and inhibited positive regulatory proteins. Correspondingly, the protein levels of p21 and p27 not only were increased in the presence of cinnamon extract, also the expression of proliferating cell nuclear antigen (PCNA) was inhibited by cinnamon extract. Besides, among the components of cinnamon extract, cinnamic acid (CA), eugenol (EG) and cinnamyl alcohol significantly inhibited the VSMC proliferation. Overall, the present study demonstrates that cinnamon extract inhibited the PDGF-BB-induced proliferation of VSMCs through a G0/G1 arrest, which down-regulated the expression of cell cycle positive regulatory proteins by up-regulating p21 and p27 expression.

scholarly journals Inhibitory Effects of Genistein on Vascular Smooth Muscle Cell Proliferation Induced by Ox-LDL: Role of BKCa Channels

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Bing Bai ◽  
Nanjuan Lu ◽  
Wei Zhang ◽  
Jinghan Lin ◽  
Tingting Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Protein Expression ◽  
Molecular Mechanism ◽  
Vascular Diseases ◽  
Nuclear Antigen ◽  
Dependent Manner ◽  
Bkca Channels ◽  
Vsmc Proliferation

Background. Oxidized low-density lipoprotein (Ox-LDL) is a crucial pathogenic factor for vascular diseases, which can induce the proliferation of vascular smooth muscle cells (VSMCs). Genistein is the main component of soybean isoflavone. Genistein has a variety of pharmacological properties in the treatment of vascular diseases and a promising clinical application. Large-conductance calcium-activated potassium (BKCa) channels are the primary type of potassium channels in VSMCs, which regulate various biological functions of VSMCs. However, whether genistein exerts an antiproliferation effect on Ox-LDL-stimulated VSMCs remains unclear. The current study is aimed at elucidating the effect of genistein on the Ox-LDL-stimulated proliferation of VSMCs and its possible molecular mechanism, especially the electrophysiological mechanism related to BKCa channels. Methods. Monoculture VSMC was obtained by an acute enzyme-dispersing method. The proliferation of cells was measured by CCK-8, cell cycle, and proliferating cell nuclear antigen (PCNA) expression. The BKCa whole-cell currents were measured by patch-clamp. Results. Ox-LDL treatment induced the proliferation of VSMCs, upregulated the BKCa protein expression, and increased the density of BKCa currents, while genistein significantly inhibited these effects caused by Ox-LDL. BKCa channels exerted a regulatory role in the proliferation of VSMCs in response to Ox-LDL. The inhibition of BKCa channels suppressed Ox-LDL-stimulated VSMC proliferation, while the activation of BKCa channels showed the opposite effect. Moreover, genistein suppressed the activity of BKCa, including protein expression and current density in a protein tyrosine kinase- (PTK-) dependent manner. Conclusion. This study demonstrated that genistein inhibited the Ox-LDL-mediated proliferation of VSMCs by blocking the cell cycle progression; the possible molecular mechanism may be related to PTK-dependent suppression of BKCa channels. Our results provided novel ideas for the application of genistein in the treatment of vascular diseases and proposed a unique insight into the antiproliferative molecular mechanism of genistein.

Inhibitory Effects of Brazilin on the Vascular Smooth Muscle Cell Proliferation and Migration Induced by PDGF-BB

2013 ◽  
Vol 41 (06) ◽  
pp. 1283-1296 ◽  
Author(s):  
Jing Guo ◽  
Li Li ◽  
Yu-Jie Wu ◽  
Yu Yan ◽  
Xiao-Na Xu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Diseases ◽  
Inhibitory Effects ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Proliferation And Migration

Abnormal vascular smooth muscle cell (VSMC) proliferation and migration contribute to the pathogenesis of vascular diseases including atherosclerosis and restenosis. Brazilin isolated from the heartwood of Caesalpinia sappan L. has been reported to exhibit various biological activities, such as anti-platelet aggregation, anti-inflammation, vasorelaxation and pro-apoptosis. However, the functional effects of Brazilin on VSMCs remain unexplored. The present study investigated the potential effects of Brazilin on platelet-derived growth factor (PDGF)-BB induced VSMC proliferation and migration as well as the underlying mechanism of action. VSMC proliferation and migration were measured by Crystal Violet Staining, wound-healing and Boyden chamber assays, respectively. Cell cycle was analyzed by flow cytometry. Enzymatic action of matrix metalloproteinase-9 (MMP-9) was carried out by gelatin zymography. Expression of adhesion molecules, cell cycle regulatory proteins, the phosphorylated levels of PDGF receptor β (PDGF-Rβ), Src, extracellular signal regulated kinase (ERK) and Akt were tested by immunoblotting. The present study demonstrated that pretreatment with Brazilin dose-dependently inhibited PDGF-BB stimulated VSMC proliferation and migration, which were associated with a cell-cycle arrest at G0/G1 phase, a reduction in the adhesion molecule expression and MMP-9 activation in VSMCs. Furthermore, the increase in PDGF-Rβ, Src, ERK1/2 and Akt phosphorylation induced by PDGF-BB were suppressed by Brazilin. These findings indicate that Brazilin inhibits PDGF-BB induced VSMC proliferation and migration, and the inhibitory effects of Brazilin may be associated with the blockade of PDGF-Rβ - ERK1/2 and Akt signaling pathways. In conclusion, the present study implicates that Brazilin may be useful as an anti-proliferative agent for the treatment of vascular diseases.

Abstract 173: MicroRNA-365 Inhibits the Proliferation of Vascular Smooth Muscle Cells by Targeting Cyclin D1

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Myung-Hyun Kim ◽  
Onju Ham ◽  
Se-Yeon Lee ◽  
Eunmi Choi ◽  
Chang Yeon Lee ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cyclin D1 ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Nuclear Antigen ◽  
Neointimal Formation ◽  
Vsmc Proliferation

Background: Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a common feature of disease progression in atherosclerosis. Cell proliferation is regulated by cell cycle regulatory proteins. MicroRNAs (miRNAs) have been reported to act as important gene regulators and play essential roles in the proliferation and migration of VSMCs in cardiovascular disease. However, the roles and mechanisms of miRNAs in VSMCs and neointimal formation are far from being fully understood. Methods & Results: In this study, cell cycle specific cyclin D1 was found to be a potential target of miR-365 by direct binding. Through an in vitro experiment, we showed that exogenous miR-365 overexpression reduced VSMC proliferation and proliferating cell nuclear antigen (PCNA) expression, while miR-365 was observed to block G1/S transition in platelet-derived growth factor (PDGF)-induced VSMCs. In addition, the proliferation of VSMCs by various stimuli, including PDGF, angiotensin II (Ang II), and serum, led to the downregulation of miR-365 expression levels. The expression of miR-365 was confirmed in balloon injured carotid arteries. Taken together, our results suggest an anti-proliferative role for miR-365 in VSMC proliferation, at least partly via modulating the expression of cyclin D1. Conclusions: Therefore, miR-365 may influence neointimal formation in atherosclerosis patients.

scholarly journals MiR-638 repressed vascular smooth muscle cell glycolysis by targeting LDHA

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 663-672 ◽  
Author(s):  
Shiyuan Chen ◽  
Hu Chen ◽  
Chaowen Yu ◽  
Ran Lu ◽  
Tao Song ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Cell Counting ◽  
Nuclear Antigen ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Luciferase Reporter Gene ◽  
Ki 67 ◽  
Gene Assay

AbstractBackgroundAbnormal proliferation and migration of vascular smooth muscle cells (VSMCs) accelerated vascular diseases progression, like atherosclerosis and restenosis. MicroRNAs were reported to participate in modulating diverse cellular processes. Here, we focused on exploring the role of miR-638 in VSMCs glycolysis and underlying mechanism.MethodsCell Counting Kit-8 (CCK-8) assay was used to measure cell viability. Western blot assay was conducted to determine the expression of cell proliferation markers proliferating cell nuclear antigen (PCNA) and Ki-67, as well as Lactate dehydrogenase A (LDHA). VSMCs migration and invasion were evaluated by Transwell assay. Luciferase reporter gene assay and RNA immunoprecipitation were performed to validate the target relationship between miR-638 and LDHA. LDHA and miR-638 expression were also determined. Glycolysis of VSMCs was tested by corresponding Kits.ResultsPlatelet-derived growth factor-bb (PDGF-bb) promoted the VSMCs viability and down-regulated miR-638. Overexpression of miR-638 inhibited cell proliferation, migration and invasion of VSMCs. LDHA was identified as a target of miR-638, and counter-regulated by miR-638. Loss of miR-638 attenuated the suppressor effects on the proliferation, migration and invasion of VSMCs induced by LDHA down-regulation. MiR-638 inhibited the glycolysis of VSMCs by targeting LDHA.ConclusionMiR-638 is down-regulated by PDGF-bb treatment and suppressed the glycolysis of VSMCs via targeting LDHA.

scholarly journals Long-acting progestin-only contraceptives impair endometrial vasculature by inhibiting uterine vascular smooth muscle cell survival

2015 ◽  
Vol 112 (16) ◽  
pp. 5153-5158 ◽  
Author(s):  
Umit A. Kayisli ◽  
Murat Basar ◽  
Ozlem Guzeloglu-Kayisli ◽  
Nihan Semerci ◽  
Helen C. Atkinson ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Nuclear Antigen ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Long Acting ◽  
Proliferation And Migration

Molecular mechanisms responsible for abnormal endometrial vasculature in women receiving long-acting progestin-only contraceptives (LAPCs) are unknown. We hypothesize that LAPCs impair vascular smooth muscle cell (VSMC) and pericyte proliferation and migration producing thin-walled hyperdilated fragile microvessels prone to bleeding. Proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (αSMA) double-immunostaining assessed VSMC differentiation and proliferation in endometria from women before and after DepoProvera (Depo) treatment and from oophorectomized guinea pigs (OVX-GPs) treated with vehicle, estradiol (E2), medroxyprogesterone acetate (MPA), or E2+MPA. Whole-genome profiling, proliferation, and migration assays were performed on cultured VSMCs treated with MPA or etonogestrel (ETO). Endometrial vessels of Depo-administered women displayed reduced αSMA immunoreactivity and fewer PCNA (+) nuclei among αSMA (+) cells (P < 0.008). Microarray analysis of VSMCs identified several MPA- and ETO-altered transcripts regulated by STAT1 signaling (P < 2.22 × 10−6), including chemokine (C-C motif) ligand 2 (CCL2). Both MPA and ETO reduce VSMC proliferation and migration (P < 0.001). Recombinant CCL2 reversed this progestin-mediated inhibition, whereas a STAT1 inhibitor abolished the CCL2 effect. Similarly, the endometria of MPA treated OVX-GPs displayed decreased αSMA staining and fewer PCNA (+) nuclei in VSMC (P < 0.005). In conclusion, LAPCs promote abnormal endometrial vessel formation by inhibiting VSMC proliferation and migration.

MiR-506-3p Promotes the Proliferation and Migration of Vascular Smooth Muscle Cells via Targeting KLF4

Pathobiology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Hang Dong ◽  
Guangyu Jiang ◽  
Jiayue Zhang ◽  
Yuming Kang
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Qrt Pcr ◽  
And Migration ◽  
Proliferation And Migration

<b><i>Background:</i></b> The dysregulation of proliferation and migration of vascular smooth muscle cells (VSMCs) is one of the major causes of atherosclerosis (AS). Accumulating studies confirm that Kruppel-like factor 4 (KLF4) can regulate the proliferation and differentiation of VSMCs through multiple signaling pathways. However, the mechanism of KLF4 dysregulation remains unknown. <b><i>Methods:</i></b> Apolipoprotein E-knockout (ApoE<sup>−/−</sup>) mice and human VSMCs were used to establish AS animal model and cell model, respectively. qRT-PCR was employed to determine the expressions of miR-506-3p and KLF4. Cell Counting Kit -8, Transwell, TUNEL assays, and flow cytometry were performed to measure the proliferation, migration, and apoptosis of VSMCs. The upstream miRNAs of KLF4 were predicted by microT, miRanda, miRmap, and TargetScan databases. The interaction between KLF4 and miR-506-3p was confirmed using qRT-PCR, Western blot, and luciferase reporter gene assay. <b><i>Results:</i></b> KLF4 expression was significantly decreased in the VSMCs of ApoE<sup>−/−</sup> mice fed with high-fat diet and in human VSMCs treated with oxidized low-density lipoprotein in time-dependent and dose-dependent manners. The transfection of miR-506-3p mimics or KLF4 shRNA promoted the proliferation and migration of VSMCs but inhibited the apoptosis while miR-506-3p inhibitors and pcDNA3.1-KLF4 exerted opposite effects. Additionally, KLF4 was confirmed as a target gene of miR-506-3p and could be negatively regulated by miR-506-3p. <b><i>Conclusion:</i></b> MiR-506-3p can promote the proliferation and migration of VSMCs via targeting KLF4, which can probably contribute to the pathogenesis of AS.

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