• Molecules and Cells
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• v.42 no.3
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• pp.218-227
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• 2019

This study was designed to determine the effects of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) on vascular smooth muscle cell (VSMC) apoptosis and extracellular matrix (ECM) disruption in a murine abdominal aortic aneurysm (AAA) model. After injection of PVT1-silencing lentiviruses, AAA was induced in Apolipoprotein E-deficient ($ApoE^{-/-}$) male mice by angiotensin II (Ang II) infusion for four weeks. After Ang II infusion, mouse serum levels of pro-inflammatory cytokines were analysed, and aortic tissues were isolated for histological, RNA, and protein analysis. Our results also showed that PVT1 expression was significantly upregulated in abdominal aortic tissues from AAA patients compared with that in controls. Additionally, Ang II treatment significantly increased PVT1 expression, both in cultured mouse VSMCs and in AAA murine abdominal aortic tissues. Of note, the effects of Ang II in facilitating cell apoptosis, increasing matrix metalloproteinase (MMP)-2 and MMP-9, reducing tissue inhibitor of MMP (TIMP)-1, and promoting switching from the contractile to synthetic phenotype in cultured VSMCs were enhanced by overexpression of PVT1 but attenuated by knockdown of PVT1. Furthermore, knockdown of PVT1 reversed Ang II-induced AAA-associated alterations in mice, as evidenced by attenuation of aortic diameter dilation, marked adventitial thickening, loss of elastin in the aorta, enhanced aortic cell apoptosis, elevated MMP-2 and MMP-9, reduced TIMP-1, and increased pro-inflammatory cytokines. In conclusion, our findings demonstrate that knockdown of lncRNA PVT1 suppresses VSMC apoptosis, ECM disruption, and serum pro-inflammatory cytokines in a murine Ang II-induced AAA model.

• Bulletin of the Korean Chemical Society
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• v.34 no.9
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• pp.2707-2710
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• 2013

The present communication deals with development of ten novel N-Phenyl-3-Pyridin-2-yl imino derivatives as vascular smooth muscle relaxants. The derivatives were prepared and optimized using pocket modelling and pharmacophore modelling. The 4 hydroxy substituted derivatives are showed potent activity comparable to the sildenafil.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.11a
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• pp.119-119
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• 2004

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.119-119
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• 2002

Several 1,4-naphthoquinone derivatives have been reported to possess many pharmacological effects such as anti-viral, anti-fungal, anti-cancer and anti-platelet activities. However, little has been known about functional role in vascular smooth muscle cells (VSMCs).(omitted)

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.193-201
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• 2018

Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is considered to mediate fibrosis through extracellular matrix (ECM) synthesis in diabetic cardiovascular complications. Statins have significant immunomodulatory effects and reduce vascular injury. We therefore examined whether fluvastatin has anti-fibrotic effects in vascular smooth muscle cells (VSMCs) and elucidated its putative transduction signals. We show that advanced glycation end products (AGEs) stimulated CTGF mRNA and protein expression in a time-dependent manner. AGE-induced CTGF expression was mediated via ERK1/2, JNK, and Egr-1 pathways, but not p38; consequently, cell proliferation and migration and ECM accumulation were regulated by CTGF signaling pathway. AGE-stimulated VSMC proliferation, migration, and ECM accumulation were blocked by fluvastatin. However, the inhibitory effect of fluvastatin was restored by administration of CTGF recombinant protein. AGE-induced VSMC proliferation was dependent on cell cycle arrest, thereby increasing G1/G0 phase. Fluvastatin repressed cell cycle regulatory genes cyclin D1 and Cdk4 and augmented cyclin-dependent kinase inhibitors p27 and p21 in AGE-induced VSMCs. Taken together, fluvastatin suppressed AGE-induced VSMC proliferation, migration, and ECM accumulation by targeting CTGF signaling mechanism. These findings might be evidence for CTGF as a potential therapeutic target in diabetic vasculature complication.

• Preventive Nutrition and Food Science
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• v.19 no.4
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• pp.363-366
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• 2014

Zinc is considered to be involved in maintaining healthy vascular condition. Atherosclerotic calcification of vascular smooth muscle cells (VSMCs) occurs via the mechanism of cell death; therefore, cell viability is a critical factor for preventing VSMC calcification. In this study, we tested whether zinc affected VSMC viability under both normal physiological non-calcifying (0 mM P) and atherosclerotic calcifying conditions (3 and 5 mM P), since VSMC physiological characters change during the VSMC calcification process. The study results showed that an optimal zinc level ($15{\mu}M$) restored the decreased VSMC viability which was induced under low zinc levels (0 and $1{\mu}M$) and calcifying conditions (3 and 5 mM P) at 9 and 15 days culture. This zinc-protecting effect for VSMC viability is more prominent under atherosclerotic calcifying condition (3 and 5 mM P) than normal condition (0 mM P). Also, the increased VSMC viability was consistent with the decreased Ca and P accumulation in VSMC cell layers. The results suggested that zinc could be an effective biomineral for preventing VSMC calcification under atherosclerotic calcifying conditions.

• BMB Reports
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• v.55 no.5
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• pp.244-249
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• 2022

Characterized by abnormal proliferation and migration of vascular smooth muscle cells (VSMCs), neointima hyperplasia is a hallmark of vascular restenosis after percutaneous vascular interventions. Vaccinia-related kinase 1 (VRK1) is a stress adaption-associated ser/thr protein kinase that can induce the proliferation of various types of cells. However, the role of VRK1 in the proliferation and migration of VSMCs and neointima hyperplasia after vascular injury remains unknown. We observed increased expression of VRK1 in VSMCs subjected to platelet-derived growth factor (PDGF)-BB by western blotting. Silencing VRK1 by shVrk1 reduced the number of Ki-67-positive VSMCs and attenuated the migration of VSMCs. Mechanistically, we found that relative expression levels of β-catenin and effectors of mTOR complex 1 (mTORC1) such as phospho (p)-mammalian target of rapamycin (mTOR), p-S6, and p-4EBP1 were decreased after silencing VRK1. Restoration of β-catenin expression by SKL2001 and re-activation of mTORC1 by Tuberous sclerosis 1 siRNA (siTsc1) both abolished shVrk1-mediated inhibitory effect on VSMC proliferation and migration. siTsc1 also rescued the reduced expression of β-catenin caused by VRK1 inhibition. Furthermore, mTORC1 re-activation failed to recover the attenuated proliferation and migration of VSMC resulting from shVrk1 after silencing β-catenin. We also found that the vascular expression of VRK1 was increased after injury. VRK1 inactivation in vivo inhibited vascular injury-induced neointima hyperplasia in a β-catenin-dependent manner. These results demonstrate that inhibition of VRK1 can suppress the proliferation and migration of VSMC and neointima hyperplasia after vascular injury via mTORC1/β-catenin pathway.

• Journal of Korean Neurosurgical Society
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• v.38 no.5
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• pp.375-379
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• 2005

Objective : Papaverine has been used in treating vasospasm following subarachnoid hemorrhage[SAH]. However, its action mechanism for cerebral vascular relaxation is not clear. Potassium channels are closely related to the contraction and relaxation of cerebral smooth muscle. Therefore, to identify the role of potassium and calcium channels in papaverine-induced vascular relaxation, we examine the effect of papaverine on potassium channels in freshly isolated smooth muscle cells from rat basilar artery. Methods : The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. Papaverine was added to the bath solution. Results : Papaverine of $100{\mu}M$ into bath solution increased the amplitude of the outward $K^+$ current which was completely blocked by BKCa[large conductance calcium dependent potassium channels]blocker, IBX[iberiotoxin], and calcium chealator, BAPTA[l,2-bis[o-aminophenoxy]ethane-N,N,N',N'-tetraacetic acid], in whole cell mode. Conclusion : These results strongly suggest that potassium channels may play roles in papaverine-induced vascular relaxation in rat basilar artery.

• 대한약리학회:학술대회논문집
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• 2006.10a
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• pp.113.1-113.1
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• 2006

• Nutrition Research and Practice
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• v.8 no.5
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• pp.521-525
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• 2014

BACKGROUND/OBJECTIVES: Artemisinin (AT), an active compound in Arternisia annua, is well known as an anti-malaria drug. It is also known to have several effects including anti-oxidant, anti-inflammation, and anti-cancer activities. To date, the effect of AT on vascular disorders has not been studied. In this study, we investigated the effects of AT on the migration and proliferation of vascular smooth muscle cells (VSMC) stimulated by platelet-derived growth factor BB (PDGF-BB). MATERIALS/METHODS: Aortic smooth muscle cells were isolated from Sprague-Dawley rats. PDGF-BB stimulated VSMC migration was measured by the scratch wound healing assay and the Boyden chamber assay. Cell viability was determined by using an EZ-Cytox Cell Viability Assay Kit. The production of reactive oxygen species (ROS) in PDGF-BB stimulated VSMC was measured through $H_2DCF$-DA staining. We also determined the expression levels of signal proteins relevant to ROS, including measures of extracellular signal-regulated kinase (ERK) 1/2 measured by western blot analysis and matrix metalloproteinase (MMP) 9 measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: AT ($10{\mu}M$ and $30{\mu}M$) significantly reduced the proliferation and migration of PDGF-BB stimulated VSMC in a dose-dependent manner. The production of ROS, normally induced by PDGF-BB, is reduced by treatment with AT at both concentrations. PDGF-BB stimulated VSMC treated with AT ($10{\mu}M$ and $30{\mu}M$) have reduced phosphorylation of ERK1/2 and inhibited MMP9 expression compared to untreated PDGF-BB stimulated VSMC. CONCLUSIONS: We suggest, based on these results, that AT may exert an anti-atherosclerotic effect on PDGF-BB stimulated VSMCs by inhibiting their proliferation and migration through down-regulation of ERK1/2 and MMP9 phosphorylation.