• 한국식물생명공학회:학술대회논문집
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• 한국식물생명공학회 2004년도 생명공학 실용화를 위한 비젼
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• pp.81-90
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• 2004

Sialic acid containing glycosphingolipids (gangliosides) have been implicated in the regulation of various biological phenomena such as atherosclerosis. Recent report suggeststhat exogenously supplied disialoganglioside (GD3) serves a dual role in vascular smooth muscle cells (VSMC) proliferation and apoptosis. However, the role of the GD3 synthase gene in VSMC responses has not yet been elucidated. To determine whether a ganglioside is able to modulate VSMC growth. the effect of overexpression of the GD3 synthase gene on DNA synthesis was examined. The results show that the overexpression of this gene has a potent inhibitory effect on DNA synthesis and ERK phosphorylation in cultured VSMC in the presence of PDGF. The suppression of the GD3 synthase gene was correlated with the down-regulation of cyclinE/CDK2. the up-regulation of the CDK inhibitor p21 and blocking of the p27 inhibition,whereas up-regulation of p53 as the result of GD3 synthase gene expression was not observed. Consistently, blockade of GD3 function with anti-GD3 antibody reversed VSMC proliferation and cell cycle proteins. The expression of the CD3 synthase gene also led to the inhibition of TNF--induced matrix metalloproteinase-9 (MMP-9) expression in VSMC as determined by zymography and immunoblot. Furthermore, GD3 synthase gene expression strongly decreased MMP-9 promoteractivlty in response to TNF-. This inhibition was characterized by the down-regulation of MMP-9,which was Iranscriptionally regulated at NF-B and activation protein-1 (AP-1) sites in the MMP-9promoter Finally, the overexpression of MMP-9 in GD3 synthase transfectant cells rescued VSMC proliferation. However MMP-2 overexpression was not affected the cell proliferation. These findings suggest that the fl13 synthase gene represents a physiological modulator of VSMC responses that may contribute to plaque instability in atherosclerosis.

• Journal of Acupuncture Research
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• 제23권2호
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• pp.139-157
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• 2006

In the present study, I have investigated the bee venom (BV) and melittin (a major component of BV) -mediated anti-proliferative effects, and defined its mechanisms of action in cultured rat aortic vascular smooth muscle cells (VSMCs). BV and melittin $(0.4{\sim}0.8\;{\mu}g/ml)$ effectively inhibited 50 ng/ml platelet derived growth factor BB (PDGF-BB)-induced VSMCs proliferations. The regulation of apoptosis has attracted much attention as a possible means of eliminating excessively proliferating VSMCs. In the present study, the treatment of BV and melittin strongly induced apoptosis of VSMCs. I examined the effects on $NF-{\kappa}B$ activation to investigate a possible mechanism for anti-proliferative effects of BV and melittin, the PDGF-BB-induced $I{\kappa}B{\alpha}$ phosphorylation and its degradation were potently inhibited by melittin, and DNA binding activity and nuclear translocation of $NF-{\kappa}B$ p50 subunit in response to the action of PDGF-BB were potently attenuated by melittin. In further investigations, melittin markedly inhibited the PDGF-BB-induced phosphorylation of Akt but not ERK1/2, upstream signals of $NF-{\kappa}B$. Treatment of melittin also potently induced pro-apoptotic protein p53, Bax, and caspase-3 expression, but decreased anti-apoptotic protein Bcl-2 expression. These results suggest that the anti-proliferative effects of BV and melittin in VSMCs through induction of apoptosis via suppressions of $NF-{\kappa}B$ and Akt activation, and enhancement of apoptotic signal pathway. Based on these results, BV acupuncture can be a candidate as a therapeutic method for restenosis and atherosclerosis.

• 대한의용생체공학회:의공학회지
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• 제27권5호
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• pp.224-228
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• 2006

The object of this study is to investigate the potential of dual-electrospun polymer based structure for vascular tissue engineering, especially for the medium or small sue blood vessels. Polyurethane(PU), which is known to be biocompatible in this area, was electrospun with poly(ethylene oxide) (PEO). Concentration of PU was fixed at 20wt%, while that of PEO was set from 15 to 35wt%. Morphological features were observed by SEM image and measurement of porosity and cellular responses were tested before and after extracting PEO from the hybrid scaffolds by immersing the scaffolds into distilled water. The diameter of PEO fibers were ranged from 200nm to 500nm. The lower concentration of PEO tended to show beads. The porosity of the scaffolds after extracting PEO was highly increased with higher concentration of PEO as expected. Also, higher proliferation rate of smooth muscle cells was observed at higher concentration of PEO than at the lower concentration and without PEO. As conclusions, this dual electrospinning technique combined with PU and PEO is expected to overcome the current barrier of cell penetration by providing more space for cells to proliferation.

• The Korean Journal of Physiology and Pharmacology
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• 제25권1호
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• pp.27-38
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• 2021

Excessive salt intake induces hypertension, but several gamma-aminobutyric acid (GABA) supplements have been shown to reduce blood pressure. GABA-salt, a fermented salt by L. brevis BJ20 containing GABA was prepared through the post-fermentation with refined salt and the fermented GABA extract. We evaluated the effect of GABA-salt on hypertension in a high salt, high cholesterol diet induced mouse model. We analyzed type 1 macrophage (M1) polarization, the expression of M1 related cytokines, GABA receptor expression, endothelial cell (EC) dysfunction, vascular smooth muscle cell (VSMC) proliferation, and medial thicknesses in mice model. GABA-salt attenuated diet-induced blood pressure increases, M1 polarization, and TNF-α and inducible nitric oxide synthase (NOS) levels in mouse aortas, and in salt treated macrophages in vitro. Furthermore, GABA-salt induced higher GABAB receptor and endothelial NOS (eNOS) and eNOS phosphorylation levels than those observed in salt treated ECs. In addition, GABA-salt attenuated EC dysfunction by decreasing the levels of adhesion molecules (E-selectin, Intercellular Adhesion Molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1]) and of von Willebrand Factor and reduced EC death. GABA-salt also reduced diet-induced reductions in the levels of eNOS, phosphorylated eNOS, VSMC proliferation and medial thickening in mouse aortic tissues, and attenuated Endothelin-1 levels in salt treated VSMCs. In summary, GABA-salt reduced high salt, high cholesterol diet induced hypertension in our mouse model by reducing M1 polarization, EC dysfunction, and VSMC proliferation.

• The Korean Journal of Physiology and Pharmacology
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• 제26권3호
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• pp.183-193
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• 2022

MicroRNAs (miRNAs) regulate gene expression and are biomarkers for coronary atherosclerosis (AS). A novel miRNA-mRNA regulation network of coronary AS still needs to be disclosed. The aim of this study was to analyze potential mRNAs in coronary AS patients and the role of their upstream miR-491-5p in vascular smooth muscle cells (VSMCs). We first confirmed top ten mRNAs according to the analysis from Gene Expression Omnibus database (GSE132651) and examined the expression levels of them in the plaques and serum from AS patients. Five mRNAs (UBE2G2, SLC16A3, POLR2C, PNO1, and AMDHD2) presented significantly abnormal expression in both plaques and serum from AS patients, compared with that in the control groups. Subsequently, they were predicted to be targeted by 11 miRNAs by bioinformatics analysis. Among all the potential upstream miRNAs, only miR-491-5p was abnormally expressed in the plaques and serum from AS patients. Notably, miR-491-5p overexpression inhibited viability and migration, and significantly increased the expression of contractile markers (α-SMA, calponin, SM22α, and smoothelin) in VSMCs. While silencing miR-491-5p promoted viability and migration, and significantly suppressed the expression of α-SMA, calponin, SM22α, and smoothelin. Overall, miR-491-5p targeted UBE2G2, SLC16A3, and PNO1 and regulated the dysfunctions in VSMCs.

• The Korean Journal of Physiology and Pharmacology
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• 제5권2호
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• pp.147-156
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• 2001

It has been proposed that $Ca^{2+}-activated$ K $(K_{Ca})$ channels play an essential role in vascular tone. The alterations of the properties of coronary $K_{Ca}$ channels have not been studied as a possible mechanism for impaired coronary reserve in cardiac hypertrophy. The present studies were carried out to determine the properties of coronary $K_{Ca}$ channels in normal and hypertrophied hearts. These channels were measured from rabbit coronary smooth muscle cells using a patch clamp technique. The main findings of the present study are as follows: (1) the unitary current amplitudes and the slope conductance of coronary $K_{Ca}$ channels were decreased without changes of the channel kinetics in isoproterenol-induced cardiac hypertrophy; (2) the sensitivity of coronary $K_{Ca}$ channels to the changes of intracellular concentration of $Ca^{2+}$ was reduced in isoproterenol-induced cardiac hypertrophy. From above results, we suggest for the first time that the alteration of $K_{Ca}$ channels are involved in impaired coronary reserve in isoproterenol-induced cardiac hypertrophy.

• The Journal of Korean Physical Therapy
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• 제15권4호
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• pp.442-454
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• 2003

The aim of this study was to demonstrate the effects of silver spike point (SSP) low frequency electrical stimulation on plasma vasoactive intestinal polypeptide (VIP) activities measured by radioimmunoassay from volunteer and the effects of VIP on pain substance-induced contraction investigated by isometric tension methode in animal. The current of 3 Hz continue type, but not 100 Hz continue type, of SSP low frequency electrical stimulation significantly increased in plasma VIP from normal volunteer. The pain substance, such as norepinephrine, serotonin, and prostaglandin $F2{\alpha}$, increased vascular smooth muscle contraction, respectively. These responses were inhibited by VIP applied cumulatively (1 nM - $1\;{\mu}M$), but not serotonin-induced contraction. In addition, serotonin, and prostaglandin $F2{\alpha}$ induced uterine smooth muscle contraction from rat. However, these responses were inhibited by VIP ($1\;{\mu}M$), only serotonin-induced contraction. These results suggest that the VIP regulates pain substance in part and that the SSP low frequency electrical stimulation, specifically current of 3 Hz continue type, significantly increases plasma VIP from volunteer.

• The Korean Journal of Physiology and Pharmacology
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• 제4권6호
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• pp.463-469
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• 2000

It has been well known that 4-aminopyridine (4-AP) has an excitatory effect on vascular smooth muscle due to causing membrane depolarization by blocking $K^+-channel$. However, we observed that 4-AP had an inhibitory effect on the mesenteric artery of rat. Therefore, we investigated the mechanism of 4-AP-induced vasorelaxation. The mesenteric arcuate artery and its branches were isolated and cut into ring. The ring segment was immersed in HEPES-buffered solution and its isometric tension was measured. 4-AP $(0.1{\sim}10\;mM)$ induced a concentration-dependent relaxation, which was unaffected by NO synthase inhibitor, $N^G-nitro-L-arginine$ methylester $(100\;{\mu}M)$ or soluble guanylate cyclase inhibitor, methylene blue $(100\;{\mu}M).$ Glibenclamide $(100\;{\mu}M)$, ATP-sensitive $K^+$ channel blocker, did not exert any effect on the 4-AP-induced vasorelaxation. 4-AP relaxed the sustained contraction induced by 100 mM $K^+$ or $Ca^{2+}$ ionophore, A23187 $(100\;{\mu}M)$ in a dose-dependent manner. In addition, 4-AP significantly decreased the phasic contractile response to norepinephrine in the absence of extracellular $Ca^{2+}$. However, 4-AP did not block the $^{45}Ca$ influx of rat aorta. From the above results, we suggest that 4-AP may not block the $Ca^{2+}$ influx through $Ca^{2+}-channel,$ but act as a nonspecific vasorelaxant in arterial smooth muscle.

• Archives of Plastic Surgery
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• 제36권4호
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• pp.493-496
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• 2009

Purpose: Glomus tumors are neoplasms that are composed of modified smooth muscle cells of the glomus body and multiple glomus tumor comprises 10% of all glomus tumors. We report a case of disseminated multiple glomus tumors. Methods: A 14 - year - old boy presented with multiple subcutaneous purple nodules on the right cheek, back, right arm, right hand dorsum, right fourth finger, and left ankle. Nodules on the back and right fourth finger were completely excised under local anesthesia and histopathologic examination was followed. Results: Histopathologic findings showed numerous dilated, cavernous - like, thin - walled, vascular spaces surrounded by one or a few layers of glomus cells. On immunohistochemical examination, glomus cells stain for smooth muscle actin, and endothelial cells stain for CD31. Those revealed multiple glomangiomas. Conclusion: A review of Korean literature revealed only one reported cases of disseminated multiple glomus tumors, so this is the second case to be reported in the Korean literature. In case of multiple soft tissue tumors, thorough physical examination and preoperative evaluation is needed.

• The Korean Journal of Physiology and Pharmacology
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• 제5권1호
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• pp.33-40
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• 2001

The aim of present study was to define the cellular mechanisms underlying changes in delayed rectifier $K^+\;(K_{DR})$ channel function in isoproterenol-induced hypertrophy. It has been proposed that $K_{DR}$ channels play a role in regulation of vascular tone by limiting membrane depolarization in arterial smooth muscle cells. The alterations of the properties of coronary $K_{DR}$ channels have not been studied as a possible mechanism for impaired coronary reserve in cardiac hypertrophy. The present study was carried out to compare the properties of coronary $K_{DR}$ channels in normal and hypertrophied hearts. These channels were measured from rabbit coronary smooth muscle cells using a patch clamp technique. The main findings of the study are as follows: (1) the $K_{DR}$ current density was decreased without changes of the channel kinetics in isoproterenol-induced hypertrophy; (2) the sensitivity of coronary $K_{DR}$ channels to 4-AP was increased in isoproterenol-induced hypertrophy. From the above results, we suggest for the first time that the alteration of $K_{DR}$ channels may limit vasodilating responses to several stimuli and may be involved in impaired coronary reserve in isoproterenol-induced hypertrophy.