• Journal of Korean Neurosurgical Society
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• v.39 no.3
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• pp.215-220
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• 2006

Objective : Tyrosine kinase inhibitors may be useful in the management of cerebral vasospasm. It has not yet been reported whether L-type $Ca^{2+}$ channels playa role in tyrosine kinase inhibitors-induced vascular relaxation of cerebral artery. This study was undertaken to clarify the role of L-type $Ca^{2+}$ channels in tyrosine kinase inhibitors-induced vascular relaxation, and to investigate the effect of tyrosine kinase inhibitors on L-type $Ca^{2+}$ channels currents 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. Results : Patch clamp studies revealed a whole-cell current which resembles the L-type $Ca^{2+}$ current reported by others. The amplitude of this current was decreased by nimodipine and increased by Bay K 8644. Genistein[n=5], tyrphostin A-23[n=3]. A-25[n=6] $30{\mu}M$ reduced the amplitude of the L -type $Ca^{2+}$ channel current in whole cell mode. In contrast, diadzein $30{\mu}M$ [n=3]. inactive analogue of genistein, did not decrease the amplitude of the L-type $Ca^{2+}$ channels current. Conclusion : These results suggest that tyrosine kinase inhibitors such as genistein, tyrphostin A-23, A-25 may relax cerebral vessel through decreasing level of intracellular calcium, [$Ca^{2+}$]i, by inhibition of L-type $Ca^{2+}$ channel.

• 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 Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.974-979
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• 2009

Proliferation of vascular smooth muscle cell(VSMC) is one of the key features in onset of atherosclerosis and restenosis after vascular surgery such as stent implant. Atherosclerotic plaques are usually composed of collagen, elatsin and smooth muscle cells. Release of matrix metalloproteinases(MMPs) is considered to have correlation with development of atherosclerotic plaques. Based on the hypothesis that MMP inhibition would be helpful in the treatment of atherosclerosis, we investigated inhibition of MMP activity and migration of TNF-$\alpha$-induced human aortic smooth muscle cell(HASMC) by Cinnamomi Ramulus(CC). The result from gelatin zymography showed that CC inhibited MMP-9 activity in a dose-dependent manner. In addition, CC considerably inhibited the migration of HASMC induced by TNF-$\alpha$, while it showed little cytotoxic effect on HASMC. These results suggest that CC can be a potential anti-atherosclerotic agent through inhibition of MMP-9 activity and SMC migration.

• Environmental Analysis Health and Toxicology
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• v.19 no.1
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• pp.109-117
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• 2004

The purpose of the present study was to examine the effect of diesel exhaust particles on human aortic vascular smooth muscle cells (VSMCs). DNA synthesis, cell viability and morphology of VSMCs after treatment of diesel exhaust particles (DEP) and fine particulate matter (PM$_{2.5}$) were assayed. PM$_{2.5}$ inhibited the DNA synthesis of VSMCs in a concentration -dependent manner, whereat DEP did not affect VSMCs up to 50$\mu\textrm{g}$/mL. These results were confirmed by morphological examination of VSMCs. PM$_{2.5}$ showed a dose-dependent cytotoxicity of VSMCs by MTT assay. Fraction 4 (organic acids) and fraction 8 (moderately polar compounds) showed the most potent inhibition of DNA synthesis of VSMCs, and fraction 7 (slightly polar compounds), fraction 9 (higher polar compounds), and fraction 6 (aromatic compounds) were next order. These results were confirmed by morphological examination of VSMCs. These results suggest that PM$_{2.5}$ inhibits the DNA synthesis of VSMCs through the cytotoxicity.oxicity.

• Bulletin of the Korean Chemical Society
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• v.32 no.6
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• pp.2079-2082
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• 2011

• Proceedings of the Korean Society of Food Hygiene and Safety Conference
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• 2004.05a
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• pp.232-232
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• 2004

• Bulletin of the Korean Chemical Society
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• v.30 no.12
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• pp.2881-2882
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• 2009

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.108.2-108.2
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• 2003

Kaempferol, a flavonol compound, has been reported as the anti-oxidant and anti-angiogenic agent and it has been found to inhibit cell growth in vitro. Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in development of atherosclerosis. In this study, we examined the anti-proliferative effect and its mechanism on rat aortic VSMCs treated by kaempferol. kaempferol significantly inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic VSMCs in concentration-dependent manner by cell count and ［$^3$H］-thymidine incorporation assay. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.182.2-182.2
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• 2003

The abnormal proliferation and migration of vascular smooth muscle cell (SMC) play an important role in the pathology of coronary artery atherosclerosis and restenosis. Platelet-derived growth factor (PDGF) is one of the most potent promoters of the proliferation and migration of the SMC. The heterocyclic quinones represent an important class of biologically active molecules. However, the inhibitory activity of quinone classes on the proliferation of the SMC has not been reported. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.207.3-208
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• 2003

Objectives:We have reported that oral administration of Saiko-ka-Ryukotsu-Borei-To (SRB), a traditional Chinese formulation, inhibited the intimal thickening in carotid artery after balloon injury in cholesterol-fed rats. To elucidate its mechanism, the effects of SRB on migration and proliferation of vascular smooth muscle cell (VSMC) were examined in vivo and in vitro.Methods: ＜ In vivo-study＞ Rats were fed on diet containing 1% cholesterol and SRB 3 days before and 4 days after denudation. Simvastatin was used as a positive control. (omitted)