scholarly journals Plasma Small Extracellular Vesicle-Carried miRNA-501-5p Promotes Vascular Smooth Muscle Cell Phenotypic Modulation-Mediated In-Stent Restenosis

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Xiao-Fei Gao ◽  
Zhi-Mei Wang ◽  
Ai-Qun Chen ◽  
Feng Wang ◽  
Shuai Luo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Phenotypic Modulation ◽  
Vsmc Proliferation ◽  
Stent Restenosis ◽  
Coronary Stent Implantation ◽  
In Stent Restenosis

Vascular smooth muscle cell (VSMC) phenotypic modulation plays an important role in the occurrence and development of in-stent restenosis (ISR), the underlying mechanism of which remains a key issue needing to be urgently addressed. This study is designed to investigate the role of plasma small extracellular vesicles (sEV) in VSMC phenotypic modulation. sEV were isolated from the plasma of patients with ISR (ISR-sEV) or not (Ctl-sEV) 1 year after coronary stent implantation using differential ultracentrifugation. Plasma sEV in ISR patients are elevated markedly and decrease the expression of VSMC contractile markers α-SMA and calponin and increase VSMC proliferation. miRNA sequencing and qRT-PCR validation identified that miRNA-501-5p was the highest expressed miRNA in the plasma ISR-sEV compared with Ctl-sEV. Then, we found that sEV-carried miRNA-501-5p level was significantly higher in ISR patients, and the level of plasma sEV-carried miRNA-501-5p linearly correlated with the degree of restenosis ( R 2 = 0.62 ). Moreover, miRNA-501-5p inhibition significantly increased the expression of VSMC contractile markers α-SMA and calponin and suppressed VSMC proliferation and migration; in vivo inhibition of miRNA-501-5p could also blunt carotid artery balloon injury induced VSMC phenotypic modulation in rats. Mechanically, miRNA-501-5p promoted plasma sEV-induced VSMC proliferation by targeting Smad3. Notably, endothelial cells might be the major origins of miRNA-501-5p. Collectively, these findings showed that plasma sEV-carried miRNA-501-5p promotes VSMC phenotypic modulation-mediated ISR through targeting Smad3.

Abstract 239: Olfactomedin 2 Regulates Vascular Smooth Muscle Cell Phenotypic Modulation by Mediating the Interaction Between Runx2 and SRF

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Ning Shi ◽  
Xiao-Bing Cui ◽  
Shi-You Chen
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Marker Genes ◽  
Important Process ◽  
Phenotypic Modulation ◽  
And Migration ◽  
Proliferation And Migration

Olfactomedin 2 (Olfm2) is a novel regulator for vascular smooth muscle cell (SMC) differentiation, but it is unclear whether Olfm2 is also involved in SMC phenotypic modulation, an important process associated with vascular injury. In this study, we found that Olfm2 was induced during PDGF-BB-induced SMC phenotypic modulation. Olfm2 knockdown attenuated PDGF-BB-induced suppression of SM marker genes including SM myosin heavy chain and SM22α, and also inhibited PDGF-BB-stimulated SMC proliferation and migration. On the other hand, Olfm2 overexpression down-regulated SM markers gene expression, and promoted SMC proliferation marker PCNA expression. Moreover, PDGF-BB slightly induced expression of Runx2, which interfered with the formation of SRF/myocardin ternary complex, but dramatically enhanced SRF-Runx2 interaction, suggesting that certain factors mediate SRF-Runx2 interaction. Indeed, Olfm2 physically interacted with both SRF and Runx2. Blockade of Olfm2 inhibited SRF association with Runx2, leading to increased association between SRF and myocardin, which in turn activated the transcription of SM markers, whereas overexpression of Olfm2 promoted SRF binding to Runx2. These results demonstrated that Olfm2 mediates the interaction between SRF and Runx2, contributing to SMC phenotypic modulation.

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.

MiR-17 Knockdown Promotes Vascular Smooth Muscle Cell Phenotypic Modulation Through Upregulated Interferon Regulator Factor 9 Expression

2020 ◽  
Author(s):  
Wenyan Li ◽  
Ping Deng ◽  
Junhua Wang ◽  
Zhaofeng Li ◽  
Huming Zhang
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Noncoding Rna ◽  
Luciferase Assay ◽  
Marker Genes ◽  
Phenotypic Modulation ◽  
Rt Pcr

Abstract BACKGROUND MiR-17 is a small noncoding RNA that plays an important role in the development of tumorgenesis, which recently has emerged to be involved in regulation of inflammatory responses and angiogenesis. However, the effect and underlying mechanism of miR-17 on vascular smooth muscle cell (VSMC) phenotypic modulation have not been investigated. METHODS AND RESULTS In the current study, we observed that miR-17 expression tested by real-time polymerase chain reaction (RT-PCR) was downregulated in VSMCs administrated with platelet-derived growth factor-BB stimulation and carotid arteries subjected to wire injury, which were accompanied with decreased VSMC differentiation markers. Loss-of-function strategy demonstrated that miR-17 knockdown promoted VSMC phenotypic modulation characterized as decreased VSMC differentiation marker genes, increased proliferated and migrated capability of VSMC examined by RT-PCR and western blot analysis. Mechanistically, the bioinformatics analysis and luciferase assay demonstrated that miR-17 directly targeted Interferon Regulator Factor 9 (IRF9) and the upregulated IRF9 expression was responsible for the promoted effect miR-17 knockdown on VSMC phenotypic modulation. CONCLUSIONS Taken together, our results demonstrated that miR-17 knockdown accelerated VSMC phenotypic modulation partially through directly targeting to IRF9, which suggested that miR-17 may act as a novel therapeutic target for intimal hyperplasia management.

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 An essential role of PDCD4 in vascular smooth muscle cell apoptosis and proliferation: implications for vascular disease

2010 ◽  
Vol 298 (6) ◽  
pp. C1481-C1488 ◽  
Author(s):  
Xiaojun Liu ◽  
Yunhui Cheng ◽  
Jian Yang ◽  
Thomas J. Krall ◽  
Yuqing Huo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Carotid Arteries ◽  
Vascular Diseases ◽  
Vsmc Proliferation ◽  
Vascular Walls

It is well established that vascular smooth muscle cell (VSMC) apoptosis and proliferation are critical cellular events in a variety of human vascular diseases. However, the molecular mechanisms involved in controlling VSMC apoptosis and proliferation are still unclear. In the current study, we have found that programmed cell death 4 (PDCD4) is significantly downregulated in balloon-injured rat carotid arteries in vivo and in platelet-derived growth factor-stimulated VSMCs in vitro. Overexpression of PDCD4 via adenovirus (Ad-PDCD4) increases VSMC apoptosis in an apoptotic model induced by serum deprivation. In contrast, VSMC apoptosis is significantly decreased by knockdown of PDCD4 via its small interfering RNA. In the rat carotid arteries in vivo, VSMC apoptosis is increased by Ad-PDCD4. We have further identified that activator protein 1 is a downstream signaling molecule of PDCD4 that is associated with PDCD4-mediated effects on VSMC apoptosis. In addition, VSMC proliferation was inhibited by overexpression of PDCD4. The current study has identified, for the first time, that PDCD4 is an essential regulator of VSMC apoptosis and proliferation. The downregulation of PDCD4 expression in diseased vascular walls may be responsible for the imbalance of VSMC proliferation and apoptosis. The results indicate that PDCD4 may be a new therapeutic target in proliferative vascular diseases.

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