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.

scholarly journals MiR-377-3p inhibits atherosclerosis-associated vascular smooth muscle cell proliferation and migration via targeting neuropilin2

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Haijun Wang ◽  
Zheng Wei ◽  
Hulun Li ◽  
Yinghui Guan ◽  
Zhiyang Han ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Proliferation And Migration

Abstract Vascular smooth muscle cell (VSMC) proliferation and migration are vital to atherosclerosis (AS) development and plaque rupture. MicroRNA-377-3p (miR-377-3p) has been reported to inhibit AS in apolipoprotein E knockout (ApoE−/−) mice. Herein, the mechanism underlying the effect of miR-377-3p on alleviating AS is explored. In vivo experiments, ApoE−/− mice were fed with high-fat diet (HFD) to induce AS and treated with miR-377-3p agomir or negative control agomir (agomir-NC) on week 0, 2, 4, 6, 8, 10 after HFD feeding. MiR-377-3p was found to restore HFD-induced AS lesions and expressions of matrix metalloproteinase (MMP)-2, MMP-9, α-smooth muscle actin (α-actin) and calponin. In in vitro experiments, human VSMCs were tranfected with miR-377-3p agomir or agomir-NC, followed by treatment with oxidized low-density lipoprotein (ox-LDL). MiR-377-3p was observed to significantly inhibit ox-LDL-induced VSMC proliferation characterized by inhibited cell viability, expressions of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E and cell cycle transition from G1 to S phase accompanied with less 5-Ethynyl-2′-deoxyuridine (EdU)-positive cells. Furthermore, MiR-377-3p significantly inhibited ox-LDL-induced VSMC migration characterized by inhibited wound closure and decreased relative VSMC migration. Besides, neuropilin2 (NRP2) was verified as a target of miR-377-3p. MiR-377-3p was observed to inhibit NRP2 expressions in vivo and in vitro. Moreover, miR-377-3p significantly inhibited MMP-2 and MMP-9 expressions in human VSMCs. Additionally, miR-377-3p-induced inhibition of VSMC proliferation and migration could be attenuated by NRP2 overexpression. These results indicated that miR-377-3p inhibited VSMC proliferation and migration via targeting NRP2. The present study provides an underlying mechanism for miR-377-3p-based AS therapy.

Chemerin promotes the proliferation and migration of vascular smooth muscle and increases mouse blood pressure

2015 ◽  
Vol 309 (5) ◽  
pp. H1017-H1028 ◽  
Author(s):  
Hidemizu Kunimoto ◽  
Kyosuke Kazama ◽  
Mizuho Takai ◽  
Mayuko Oda ◽  
Muneyoshi Okada ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Systolic Blood Pressure ◽  
Oxidase Inhibitor ◽  
Cell Counting ◽  
And Migration ◽  
Proliferation And Migration

Blood chemerin concentration shows positive correlation not only with body mass index and serum triglyceride level but also with systolic blood pressure. While it seems likely that chemerin influences vascular smooth muscle cell (SMC) proliferation and migration, which are crucial to the development of hypertension, this remains to be clarified. In the present study, we investigated whether chemerin controls SMC proliferation and migration in vitro and also affects blood pressure in vivo. In vitro, chemerin significantly stimulated rat mesenteric arterial SMC proliferation and migration, as determined by a cell counting assay and Boyden chamber assay, respectively. The migratory effect of chemerin was confirmed in human aortic SMCs. Chemerin significantly increased ROS production in SMCs and phosphorylation of Akt (Ser473) and ERK, as measured by fluorescent staining and Western blot analysis, respectively. Various inhibitors (ROS inhibitor: N-acetyl-l-cysteine, phosphatidylinositol 3-kinase inhibitor: LY-294002, MAPKK inhibitor: PD-98059, NADPH oxidase inhibitor: gp91 ds-tat, and xanthine oxidase inhibitor: allopurinol) as well as chemokine-like receptor 1 small interfering RNA significantly inhibited chemerin-induced SMC proliferation and migration. Furthermore, chemerin-neutralizing antibody prevented carotid neointimal hyperplasia in the mouse ligation model. In vivo, chronic chemerin treatment (6 μg/kg, 6 wk) increased systolic blood pressure as well as phosphorylation of Akt and ERK in the mouse isolated aorta. In summary, we, for the first time, demonstrate that chemerin/chemokine-like receptor 1 stimulates SMC proliferation and migration via ROS-dependent phosphorylation of Akt/ERK, which may lead to vascular structural remodeling and an increase in systolic blood pressure.

Abstract 417: Adenosine Diphosphate Ribosyl Cyclase via PI3K-Akt and FOXO3a Up-regulating MMP-9 to Enhance Vascular Smooth Muscle Cell Proliferation and Migration in Mice

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Yuming Li ◽  
Haitao Li ◽  
Xinfang Wang ◽  
Junya Wang ◽  
Zhongqiu Li
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Adenosine Diphosphate ◽  
High Fat ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Proliferation And Migration

The current study was designed to explore the mechanisms of vascular smooth muscle cell (VSMC) proliferation and migration induced by adenosine diphosphate ribosyl cyclase(ADPRC). In this study, 32 Male ApoE-/- mice(6 weeks old, 18-22g)on a C57BL/6J background were divided into four groups, which received normal chow (n=8, NC group), high-fat Western-type diet (n=8, 0.25% cholesterol, 21% fat,HFD group), high-fat Western-type diet,infusion of 2,2′-dihydroxyazobenzene(DHAB, a ADPRC inhibitor, 2mg/kg/day, n=8, HFD-DHAB group) intraperitoneally or high-fat Western-type diet,infusion of LY294002(a Inhibitor of Akt, 5mg/kg/d, n=8, HFD-LY group) intraperitoneally, for 10 weeks. 8 male C57BL/6J mice served as control. After 10 weeks, mice were anesthetized with chloral hydrate, aorta was removed and immediately frozen in liquid nitrogen. Aortic atherosclerotic lesions, VSMC proliferation and migration were assessed by histomorphological observation, smooth muscle actin-α(α-SMA)and proliferating cell nuclear antigen (PCNA) examination. ADPRC expression and alterations of Akt, FOXO3a, phospho-FOXO3a and MMP-9 were determined by RT-PCR, Western Blot, Immunohistochemistry or Immunofluorescence. The results showed that, in aortic atherosclerotic lesions derived from atherosclerotic mice of HFD group, an increased VSMC proliferation and migration, reflected by the up-regulation of α-SMA and PCNA expression, were observed followed by increased expression of ADPRC, Akt, FOXO3a, phospho-FOXO3a and MMP-9. The enhanced expression of ADPRC and followed alterations of FOXO3a, phospho-FOXO3a, MMP-9 as well as α-SMA, PCNA, VSMC proliferation and migration were absent in NC group and C57BL/6J control mice. Treatment with DHAB or LY294002 reversed VSMC proliferation, migration and expression of Akt, FOXO3a, phospho-FOXO3a and MMP-9 in HFD-DHAB and HFD-LY group. These data shows that high-fat Western-type diet induced ADPRC may via PI3K-Akt to phosphorylate FOXO3a up-regulating MMP-9 to enhance vascular smooth muscle cell proliferation and migration in mice.

scholarly journals Avβ3 Single-Stranded DNA Aptamer Attenuates Vascular Smooth Muscle Cell Proliferation and Migration via Ras-PI3K/MAPK Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Hong-Bing Wu ◽  
Zhi-Wei Wang ◽  
Feng Shi ◽  
Zong-Li Ren ◽  
Luo-Cheng Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Cell Cycle Progression ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Dna Aptamer ◽  
Mitogen Activated Protein Kinase ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Proliferation And Migration

Objectives. To observe the effect of avβ3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. Background. Percutaneous transluminal coronary angioplasty (PTCA) is currently the preferred method for the treatment of coronary heart disease. However, vascular restenosis still occurs after PTCA treatment, severely affecting the clinical efficacy of PTCA. Integrin avβ3, which is widely expressed on various cell surfaces, plays an important role in the proliferation and migration of VSMCs. Methods. In this experiment, we used systematic evolution of ligands by exponential enrichment (SELEX) to screen out avβ3 ssDNA, which has high affinity and specificity to the avβ3 protein. MTT, Transwell, and cell scratch assays were carried out to examine the effect of avβ3 ssDNA on the proliferation and migration of VSMCs. Flow cytometry was performed to detect apoptosis and cell cycle progression. The effect of avβ3 ssDNA on the Ras-phosphatidylinositol-4,5-bisphosphate 3-kinase/mitogen-activated protein kinase (PI3K/MAPK) signaling pathway was evaluated by quantitative reverse transcription polymerase chain reaction and western blot. Results. In the present study, we found that avβ3 ssDNA significantly decreased the expression of osteopontin, focal adhesion kinase, Ras, p-PI3K, and p-MAPK at both mRNA and protein levels (P<0.05). Avβ3 ssDNA also inhibited VSMC proliferation and migration while promoting apoptosis (P<0.05), as demonstrated by the upregulation of the proapoptotic proteins Bax and active caspase 3 (P<0.05). Conclusions. The findings suggest that avβ3 ssDNA inhibited the proliferation and migration of VSMCs by suppressing the activation of Ras-PI3K/MAPK signaling.

TMEM98, a novel secretory protein, promotes endothelial cell adhesion as well as vascular smooth muscle cell proliferation and migration

2020 ◽  
Author(s):  
Mei Li ◽  
Hongmei Zhu ◽  
Xiaoyan Hu ◽  
Fuhua Gao ◽  
Xinxin Hu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Endothelial Cell ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Transmembrane Protein ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Proliferation And Migration

Transmembrane protein 98 (TMEM98) is a novel gene. In a prior study, we have shown that siRNA-mediated knockdown of TMEM98 inhibited interleukin (IL)-8-promoted endothelial cell (EC) adhesion as well as vascular smooth muscle cell (VSMC) proliferation and migration in the vascular endothelial and smooth muscle cells dysfunction. Herein, we used gain- and loss-of-function approaches combined with biochemical techniques to further explore the role of TMEM98 in the vascular wall cell. The expression and secretion of TMEM98 was increased in cultured human umbilical vein endothelial cells (HUVECs) and VSMCs treated with IL-8 and platelet-derived growth factor (PDGF)-BB. Also, PDGF-BB secretion was increased in TMEM98-treated HUVECs and VSMCs. Thus, it appears that TMEM98 and PDGF-BB form a positive feedback loop in potentiation of EC adhesion as well as VSMC proliferation and migration. Knockdown of TMEM98 mediated by siRNA inhibited PDGF-BB-promoted EC adhesion by downregulating the expression of ICAM-1 and VCAM-1 as well as impaired the proliferation and migration of VSMCs through suppressing the AKT/GSK3β/cyclin D1 signaling pathway and reducing the expression of β-catenin. Hence, TMEM98 promoted EC adhesion through inducing the expression of ICAM-1/VCAM-1 and triggered VSMC proliferation and migration through activating the ERK and AKT/GSK3β signaling pathways. Taken together, TMEM98 may serve as a potential therapeutic target for the clinical treatment.

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.

Sign in / Sign up

Export Citation Format

Share Document