• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.100-100
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• 2003

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. 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.

• Natural Product Sciences
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• 제26권1호
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• pp.71-78
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• 2020

The plant Dendropanax morbifera Léveille is effective folk medicines for the treatment of several conditions, such as infectious diseases, skin diseases, and other illnesses. Although the inhibitory effects of D. morbifera on the proliferation and migration of vascular smooth muscle cells (VSMCs) have been shown in our previous study, its effects in vivo remain to be elucidated. In this study, we aimed to investigate the protective effects of the extracts from D. morbifera (EDM) on neointimal hyperplasia of rat carotid artery and explore the underlying mechanisms. We observed that the ratio of intima to media thickness (I/M) was significantly decreased in the EDM-treated groups by ~80% compared to that of the control. The expression of Ki-67 and proliferating cell nuclear antigen was decreased by ~70% in the EDM-treated groups compared to that of the control. In addition, matrix metalloproteinase (MMP)2 and MMP9 significantly reduced in the neointimal layer of the EDM-treated groups. Moreover, the decreased levels of contractile phenotypic markers of VSMCs, such as α-smooth muscle actin, myocardin, and smooth muscle-myosin heavy chain, were successfully restored by EDM treatment. Furthermore, the levels of synthetic phenotypic markers, cellular retinal binding protein 1 and connexin 43 were also restored to normal levels. These results suggest that EDM inhibits vascular neointimal hyperplasia induced by balloon injury in rats via phenotypic modulation of VSMCs. Therefore, EDM may be a potential drug candidate for the prevention of restenosis.

• 대한한방내과학회지
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• 제16권1호
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• pp.104-129
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• 1995

Sabaeksan and Sabaeksangagaryureuk, a traditional prescription, has been used in Korea for many centuries as a treatment for chronic respiratory disease. The purpose of the present study was to determine the effect of Sabaeksan and Sabaeksangagaryureuk on acetylcholine-induced tracheal smooth muscle contraction in guinea pigs and norepinephrine-induced vascular smooth muscle contraction in pigs. Guinea pig (500g, female) were killed by CO2 exposure and a segment (8-10mm) of the thoracic trachea from each guinea pig and renal artery from each pig were cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 0.5g loading tension. The dose of acetylcholine (Ach) and norepinephrine (NE) which evoked 50% of maximal response ($ED_{50}$) was obtained from cumulative dose response curves for acetylcholine (10-7-10-4M) and norepinephrine (10-7-10-4M). Contractions of tracheal smooth muscle evoked by Ach ($ED_{50}$) were inhibited significantly by Sabaeksan and Sabaeksangagaryureuk. Propranolol (10-7M) slightly but significantly attenuated the inhibitory effects of Sabaeksan and Sabaeksangagaryureuk. Indomethacin and methylene blue (10-7M) did not significantly alter the inhibitory effect of Sabaeksan and Sabaeksanga-garyureuk. Contractions of vascular smooth muscle evoked by NE (NE50) were inhibited significantly by Sabaeksan and Sabaeksangagaryureuk. Propranolol (10-7M) slightly but significantly attenuated the inhibitory effects of Sabaeksan and Sabaeksangagaryureuk. Indomethacin and methylene blue (10-7M) did not significantly alter the inhibitory effect of Sabaeksan and Sabaeksangagaryureuk. These results indicate that Sabaeksan and Sabaeksangagaryureuk can relax acetylcholine-induced contraction of guinea pig tracheal smooth muscle, and norepinephrine-induced contraction of pig vascular smooth muscle that this inhibition involves, in part, the relation of adrenergic receptor.

• The Korean Journal of Physiology and Pharmacology
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• 제14권5호
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• pp.299-304
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• 2010

Losartan is a selective angiotensin II (Ang II) type 1 ($AT_1$) receptor antagonist which inhibits vascular smooth muscle cells (VSMCs) contraction and proliferation. We hypothesized that losartan may prevent cell proliferation by activating AMP-activated protein kinase (AMPK) in VSMCs. VSMCs were treated with various concentrations of losartan. AMPK activation was measured by Western blot analysis and cell proliferation was measured by MTT assay and flowcytometry. Losartan dose- and time-dependently increased the phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC) in VSMCs. Losartan also significantly decreased the Ang II- or 15% FBS-induced VSMC proliferation by inhibiting the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. Compound C, a specific inhibitor of AMPK, or AMPK siRNA blocked the losartan-induced inhibition of cell proliferation and the $G_0/G_1$ cell cycle arrest. These data suggest that losartan-induced AMPK activation might attenuate Ang II-induced VSMC proliferation through the inhibition of cell cycle progression.

• Preventive Nutrition and Food Science
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• 제18권2호
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• pp.92-97
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• 2013

The calcification of vascular smooth muscle cells (VSMCs) is considered one of the major contributors for vascular disease. Phosphate is known as the inducer for VSMC calcification. In this study, we assessed whether phosphate affected cell viability and fetuin-A, a calcification inhibitor protein, both which are related to VSMC calcification. Also, VSMC viability by zinc level was assessed. The results showed that phosphate increased Ca and P deposition in VSMCs (A7r5 cell line, rat aorta origin). This phosphate-induced Ca and P deposition was consistent with the decreased A7r5 cell viability (P<0.05), which implies phosphate-induced calcification in A7r5 cells might be due to the decreased VSMC cell viability. As phosphate increased, the protein expression of fetuin-A protein was up-regulated. A7r5 cell viability decreased as the addition of cellular zinc level was decreased (P<0.05). The results suggested that zinc deficiency causes the decreased cell viability and it would be the future study to clarify how zinc does act for VSMC cell viability. The results suggest that the decreased VSMC viability by high P or low Zn in VSMCs may be the risk factor for vascular disease.

• BMB Reports
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• 제48권6호
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• pp.354-359
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• 2015

Vascular smooth muscle cells (VSMCs) undergo death during atherosclerosis, a widespread cardiovascular disease. Recent studies suggest that oxidative damage occurs in VSMCs and induces atherosclerosis. Here, we analyzed oxidative damage repair in VSMCs and found that VSMCs are hypersensitive to oxidative damage. Further analysis showed that oxidative damage repair in VSMCs is suppressed by a low level of poly (ADP-ribosyl)ation (PARylation), a key post-translational modification in oxidative damage repair. The low level of PARylation is not caused by the lack of PARP-1, the major poly(ADP-ribose) polymerase activated by oxidative damage. Instead, the expression of poly(ADP-ribose) glycohydrolase, PARG, the enzyme hydrolyzing poly(ADP-ribose), is significantly higher in VSMCs than that in the control cells. Using PARG inhibitor to suppress PARG activity facilitates oxidative damage-induced PARylation as well as DNA damage repair. Thus, our study demonstrates a novel molecular mechanism for oxidative damage-induced VSMCs death. This study also identifies the use of PARG inhibitors as a potential treatment for atherosclerosis. [BMB Reports 2015; 48(6): 354-359]

• BMB Reports
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• 제54권11호
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• pp.569-574
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• 2021

Vascular calcification is the heterotopic accumulation of calcium phosphate salts in the vascular tissue and is highly correlated with increased cardiovascular morbidity and mortality. In this study, we found that the expression of neuromedin B (NMB) and NMB receptor is upregulated in phosphate-induced calcification of vascular smooth muscle cells (VSMCs). Silencing of NMB or treatment with NMB receptor antagonist, PD168368, inhibited the phosphate-induced osteogenic differentiation of VSMCs by inhibiting Wnt/β-catenin signaling and VSMC apoptosis. PD168368 also attenuated the arterial calcification in cultured aortic rings and in a rat model of chronic kidney disease. The results of this study suggest that NMB-NMB receptor axis may have potential therapeutic value in the diagnosis and treatment of vascular calcification.

• Journal of Yeungnam Medical Science
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• 제27권2호
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• pp.91-97
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• 2010

암세포의 전이, 죽상경화증, 당뇨성 망막병증과 같은 병적인 과정에서 혈관내피세포는 핵심적인 역할을 담당한다. 죽상경화증의 죽종 형성에 혈관민무늬근육세포가 직접적으로 관여한다. 배꼽정맥, 혈관내벽, 그리고 망막에 있는 이들 내피세포들은 다양한 효소용액들을 이용하여 얻는다. 순수하게 분리된 이들 세포는 내피세포와 관련된 질병의 시험관 내 연구에 있어 중요한 모델이다. 이러한 관점에서 볼 때 대동맥 벽의 중간막에서 분리한 후 배양한 민무늬근육세포도 죽상경화증의 발병을 설명할 수 있다. 이 종설에서는 사람배꼽정맥내피세포(HUVEC),대동맥의 내피세포 및 민무늬근육세포, 그리고 망막미세혈관내피세포(RMEC)의 분리 뿐 만 아니라 이들 세포를 이용한 질병연구에 관한 논문들을 소개하고자 한다.

• Tuberculosis and Respiratory Diseases
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• 제38권3호
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• pp.270-279
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• 1991

It has been well known that the integrity of airway epithelium is important in developing of bronchial hyperreactivity or bronchial asthma. But the mechanisms underlying this nonspecific airway hyperresponsiveness are not yet determined. To evaluate the ability of guinea pig trachea to release an epithelium derived relaxing factor (EpDRF) which relax rat vascular smooth muscle, we performed the coaxial bioassay using guinea pig trachea and rat aorta. And to evaluate the nature of EpDRF we investigate the influence of methylene blue and indomethacin on the coaxial bioassay. Results were as follows. 1) Vascular smooth muscle mounted into the epithelium intact trachea which was precontracted with phenylephrine was relaxed by addition of histamine or acetylcholine. But vascular smooth muscle mounted into epithelium denuded trachea failed to be relaxed. 2) Epithelium dependent relaxation of vascular smooth muscle was not affected by pretreatment of methylene blue or indomethacin. These results strongly suggests that guinea pig tracheal epithelium releases EpDRF which is able to relax rat vascular smooth muscle. And EpDRF released by airway epithelium is not related to endothelium derived relaxing factor (EDRF) or cyclooxygenase products.

• Journal of Microbiology and Biotechnology
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• 제14권4호
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• pp.707-714
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• 2004

How to improve the cell culture method on scaffolds is important in the tissue engineering fileld. In this study, we optimized seeding and culture methods to vascular smooth muscle cells (VSMCs) on biodegradable polymer scaffold. The primary culture of VSMCs obtained from canine external jugular vein was accomplished by applying the explant-derived method. The primary cultured VSMCs were seeded into scaffolds and then cultured by using various different methods; static or dynamic seeding, static or dynamic culture. The difference in proliferative response of VSMCs was analyzed with an alamar blue assay. Cell-polymer construct was examined by histochemical method and scanning electron microscopy. Mesh type scaffold ($10 \times 10 \times0.4 mm$) was made of polyglycolic acid (PGA) suture thread. The PGA mesh type scaffold was 45% in porosity, and 0.03 g in weight. The primary cultured VSMCs were confirmed with immunohistochemical staining using monoclonal anti-$\alpha$-smooth muscle actin. The density and distribution of proliferated VSMCs within the scaffold and cellular adherence on the surface of the scaffold showed better results in the static seeding condition than in the dynamic condition. Under the same condition of seeding method as the static condition, the dynamic culture condition showed enhanced proliferation rates of the VSMCs when compared to the static culture condition. In conclusion, to improve the VSMCs proliferation in vitro, static seeding is better than the dynamic condition. In the culture condition, however, culture under the dynamic status is better than the static condition. This was a pilot study to manufacture artificial vascular vessel by tissue engineering.