• 미생물학회지
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• 제50권3호
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• pp.223-226
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• 2014

청국장은 대두발효식품으로 대두 단백질이 발효 중 분해되면서 다양한 생리활성물질이 만들어진다. 혈관내피세포는 혈관의 기능은 물론 신생혈관 생성을 주도하는 세포이다. 뇌졸중이나 심근경색, 뇌경색 등의 혈관관련 질병들은 신생혈관 생성을 촉진하는 치료법이 필요하다. Vascular Endothelial Growth Factor (VEGF)는 새로운 혈관 형성을 촉진하는 역할을 한다. 본 연구에서는 청국장 에탄올추출물(CEE)이 HUVEC (혈관 내피세포) 증식에 미치는 영향을 조사하여 보았다. 청국장 추출물(100, $1000{\mu}g/ml$)을 HUVEC에 처리했을 때, VEGF (10 ng/ml)를 처리한 대조군과 같은 정도로 세포를 증식시켰다. 열처리한 청국장추출물을 혈관 내피세포에 처리해도 세포 증식효과는 마찬가지였다. 청국장이 세포 증식뿐 아니라 HUVEC이동에도 영향을 주는지 sprout 분석법으로 확인하였다. 청국장 추출물($100{\mu}g/ml$)을 처리했을 때, VEGF (10 ng/ml)와 비슷할 정도로 HUVEC 이동이 일어났다. 청국장 추출물에서 HUVEC 증식과 이동에 영향을 미치는 특정 peptide의 분리가 필요할 것이다.

• 생명과학회지
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• 제34권2호
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• pp.128-137
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• 2024

이 리뷰 논문에서는 혈관 투과성, 내피세포 모집, 종양관련 혈관 및 림프관의 유지 등에서 핵심적인 과정인 angiogenesis와 lymphangiogenesis에 있어서 vascular endothelial growth factors (VEGF)가 이행하는 중요한 역할에 대해 재조명하고자 한다. VEGF는 tyrosine-kinase receptor인 VEGFR-1, VEGFR-2, VEGFR-3를 통해 그 역할을 이행하며, 이러한 VEGF-VEGFR 시스템은 암에서뿐만 아니라 비정상적인 혈관 및 림프관 형성으로 인해 야기되는 다른 질병들에 있어서도 핵심적인 요소로 각광받고 있다. 암의 측면에서 보았을 때, VEGF와 그 수용체는 종양관련 혈관 및 림프관을 형성하는 과정에서 필수적이라는 점에서 치료적인 타겟으로 이목을 끌고 있다. 때문에 암세포의 성장을 방해하기 위한 항VEGF 항체, 수용체 길항체, 수용체 기능 억제제 등과 같은 여러 가지 시도들이 있었지만, 아직까지 그 임상효과가 불확실하며 더 많은 연구들이 필요한 실정이다. 이 논문에서는 VEGF의 생리적 역할을 VEGF-A, VEGF-B, VEGF-C, VEGF-D, PLGF에 따라 나누어 설명하면서 VEGF/VEGFR 시스템의 중요성을 강조한다. VEGFR-1과 VEGFR-3은 각각 angiogenesis와 lymphangiogenesis에 핵심적인 인자이며, VEGFR-2의 경우 두 가지 모두를 일으킨다. 전반적으로 이 리뷰는 현재까지 밝혀진 암을 포함한 다양한 질병에서의 VEGF와 VEGFR의 역할에 대해 상세히 설명하고자 하였다. 이를 통해 치료 표적으로서 VEGF와 VEGFR의 활용이 더욱 촉진될 것으로 기대된다.

• The Korean Journal of Physiology and Pharmacology
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• 제19권3호
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• pp.191-196
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• 2015

Attenuated functional exercise capacity in elderly and diseased populations is a common problem, and stems primarily from physical inactivity. Decreased function and exercise capacity can be restored by maintaining muscular strength and mass, which are key factors in an independent and healthy life. Resistance exercise has been used to prevent muscle loss and improve muscular strength and mass. However, the intensities necessary for traditional resistance training to increase muscular strength and mass may be contraindicated for some at risk populations, such as diseased populations and the elderly. Therefore, an alternative exercise modality is required. Recently, blood flow restriction (BFR) with low intensity resistance exercise (LIRE) has been used for such special populations to improve their function and exercise capacity. Although BFR+LIRE has been intensively studied for a decade, a comprehensive review detailing the effects of BFR+LIRE on both skeletal muscle and vascular function is not available. Therefore, the purpose of this review is to discuss previous studies documenting the effects of BFR+LIRE on hormonal and transcriptional factors in muscle hypertrophy and vascular function, including changes in hemodynamics, and endothelial function.

• BMB Reports
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• 제42권2호
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• pp.106-112
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• 2009

The bio-complex "reaction pattern in vertebrate cells"(RiV) is mainly represented by characteristic exosome-like particles - probably as reaction products of cells to specific stress. The transcription factor NF-kappaB plays a central role in inflammation. We tested the hypothesis that RiV particle preparations (RiV-PP) reduce cellular adhesion molecule (CAM) expression (ICAM-1, VCAM-1, E-selectin) by the attenuation of NF-kappaB translocation in human umbilical vein endothelial cells (HUVEC). After 4 hours, pre-incubation of HUVEC with RiV-PP before stimulation with TNF-alpha significantly reduced ICAM-1 (65.5${\pm}$10.3%) and VCAM-1 (71.1${\pm}$12.3%) mRNA expression compared to TNF-alpha-treated cells (100%, n=7). ICAM-1 surface expression was significantly albeit marginally reduced in RiV/TNF-alpha- treated cells (92.0${\pm}$5.6%, n=4). No significant effect was observed on VCAM-1 surface expression. In RiV/TNF-alpha-treated cells (n=4), NF-kappaB subunits p50 (85.7${\pm}$4.1%) and p65 (85.0${\pm}$1.8%) nuclear translocation was significantly reduced. RiV-PP may exert an anti-inflammatory effect in HUVEC by reducing CAM mRNA expression via attenuation of p50 and p65 translocation.

• The Korean Journal of Physiology and Pharmacology
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• 제3권6호
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• pp.587-595
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• 1999

This study was designed to investigate effects of calcium antagonists on endothelial and neuronal dysfunction of right coronary artery (RCA) induced by ischemia- reperfusion in anesthetized, open-chest pigs. After reperfusion, pigs were sacrificed and the RCA was rapidly dissected for in vitro experiments. Experimental groups were divided into 4 groups: control (C-RCA), ischemia-reperfusion only (I-RCA), verapamil infusion (VI-RCA) and nifedipine infusion (NI-RCA) group, respectively. The ischemia did not affect hemodynamics, mean arterial pressure, heart rate, LVdP/dtmax, and decreased RCA flow. Arterial pressure and heart rate during ischemia-reperfusion were decreased in VI-RCA and NI-RCA, and RCA flow during reperfusion was increased in NI-RCA. 5-Hydroxytryptamine (5-HT) produced concentration-dependent contractions in C-RCA. The 5-HT-induced contractions were potentiated in I-RCA and VI-RCA, but not in NI-RCA. Endothelium-dependent relaxation by calcium ionophore A23187 was inhibited in I-RCA and VI-RCA, and recovered in NI-RCA. Cyclic GMP contents were decreased in I-RCA group alone. Electrical field stimulation in C-RCA produced transient and frequency-dependent contractions and at 50 Hz caused biphasic contractions. The transient contractions were not affected by pretreatment with phentolamine and atropine, but the biphasic contraction was altered by the pretreatment. Both contractions were inhibited in I-RCA, and were partially recovered in VI-RCA and NI-RCA. Ischemia-reperfusion of RCA in pigs causes endothelial and neuronal dysfunctions, and calcium antagonists partially prevent both.

• The Korean Journal of Physiology and Pharmacology
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• 제20권2호
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• pp.169-175
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• 2016

Here, we investigated whether hyperglycemia and/or free fatty acids (palmitate, PAL) affect the expression level of bone morphogenic protein 4 (BMP4), a proatherogenic marker, in endothelial cells and the potential role of BMP4 in diabetic vascular complications. To measure BMP4 expression, human umbilical vein endothelial cells (HUVECs) were exposed to high glucose concentrations and/or PAL for 24 or 72 h, and the effects of these treatments on the expression levels of adhesion molecules and reactive oxygen species (ROS) were examined. BMP4 loss-of-function status was achieved via transfection of a BMP4-specific siRNA. High glucose levels increased BMP4 expression in HUVECs in a dose-dependent manner. PAL potentiated such expression. The levels of adhesion molecules and ROS production increased upon treatment with high glucose and/or PAL, but this eff ect was negated when BMP4 was knocked down via siRNA. Signaling of BMP4, a pro-inflammatory and pro-atherogenic cytokine marker, was increased by hyperglycemia and PAL. BMP4 induced the expression of inflammatory adhesion molecules and ROS production. Our work suggests that BMP4 plays a role in atherogenesis induced by high glucose levels and/or PAL.

• 대한한방내과학회지
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• 제27권3호
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• pp.589-602
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• 2006

Hwangryunagyotang is supposed to have significant effects on some sorts of cardiovascular diseases like atherosclerosis. For this study. ACAT inhibitor was put in LDLR -/- mice to derive free cholesterol from it. This was to examine the effectiveness of Hwangryunnagyotang on its protecting and recovering function with endothelial cells damaged by free cholesterol through experimental. The results reported below. Hwangryunagyotang suppressed the crystallization of reactive oxygen species in macrophages and the numbers of free cholesterol crystal plate structured and reduced fragmentation of nucleus in ECV 304 cell strain by ACAT inhibitor significantly. Hwangryunagyotang also suppressed the necrosis of tissue in LDLR -/- mice' (treated with ACAT inhibitor) inflammatory portion which is adjacent to aortic root, proximal aorta and carotid artery by immunohistochemistry and fluorescence microscopy. On the whole, Hwangryunagyotang suppressed the necrosis of endothelial cells and especially it's effcet for the necrosis of para-myocardial tissues by free cholesterol. With this result, I suggest Hwangryunagyotang might have protective and recovery effects on atherosclerosis, so we need to carry on this study henceforth clinically and experimentally as well.

• BMB Reports
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• 제54권10호
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• pp.516-521
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• 2021

Although arginase primarily participates in the last reaction of the urea cycle, we have previously demonstrated that arginase II is an important cytosolic calcium regulator through spermine production in a p32-dependent manner. Here, we demonstrated that rhaponticin (RPT) is a novel medicinal-plant arginase inhibitor and investigated its mechanism of action on Ca²⁺-dependent endothelial nitric oxide synthase (eNOS) activation. RPT was uncompetitively inhibited for both arginases I and II prepared from mouse liver and kidney. It also inhibited arginase activity in both aorta and human umbilical vein endothelial cells (HUVECs). Using both microscope and FACS analyses, RPT treatments induced increases in cytosolic Ca²⁺ levels using Fluo-4 AM as a calcium indicator. Increased cytosolic Ca²⁺ elicited the phosphorylations of both CaMKII and eNOS Ser1177 in a time-dependent manner. RPT incubations also increased intracellular L-arginine (L-Arg) levels and activated the CaMKII/AMPK/Akt/eNOS signaling cascade in HUVECs. Treatment of L-Arg and ABH, arginase inhibitor, increased intracellular Ca²⁺ concentrations and activated CaMKII-dependent eNOS activation in ECs of WT mice, but, the effects were not observed in ECs of inositol triphosphate receptor type 1 knockout (IP3R1^-/-) mice. In the aortic endothelium of WT mice, RPT also augmented nitric oxide (NO) production and attenuated reactive oxygen species (ROS) generation. In a vascular tension assay using RPT-treated aortic tissue, cumulative vasorelaxant responses to acetylcholine (Ach) were enhanced, and phenylephrine (PE)-dependent vasoconstrictive responses were retarded, although sodium nitroprusside and KCl responses were not different. In this study, we present a novel mechanism for RPT, as an arginase inhibitor, to increase cytosolic Ca²⁺ concentration in a L-Arg-dependent manner and enhance endothelial function through eNOS activation.

• Integrative Medicine Research
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• 제5권3호
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• pp.223-223
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• 2016

Background: Korean Red Ginseng (Panax ginseng) has been shown to exert antihypertensive effects. In particular, ginsenoside Rg3 is thought to be a potent modulator of vascular function. The present study was performed to examine the antihypertensive efficacy of Korean Red Ginseng (KRG) extract and Rg3-enriched KRG (REKRG) extract. Methods: Spontaneously hypertensive rats (SHRs) andWistar-Kyoto rats (WKYs) were divided into six groups (WKY control, WKY-KRG, WKY-REKRG, SHR control, SHR-KRG, and SHRREKRG), and systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at the carotid artery, followed by injection of 3mg/kg KRG or 3mg/kg REKRG. Results: REKRG treatment significantly decreased SBP and DBP 3hours post-treatment in the SHR group compared with SHR control group. However, SBP and DBP were not significantly different in KRG-treated SHRs compared with control SHRs. REKRG treatment did not significantly alter SBP or DBP 3hours post-treatment in the WKY group compared with WKY control group. Similarly, there were no differences in SBP or DBP with KRG treatment in the WKY group and WKY control group. Both KRG and REKRG increased endothelial nitric oxide synthase phosphorylation levels in the aorta, and the increases in endothelial nitric oxide synthase phosphorylation levels by REKRG treatment were higher than those with KRG treatment. Similarly, nitric oxide production in plasma from WKYs and SHRs was also increased by both KRG and REKRG. Conclusion: These results suggest that REKRG has a more beneficial effect on blood pressure control than KRG in SHRs.

• Biomolecules & Therapeutics
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• 제23권3호
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• pp.233-237
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• 2015

Shikonin, a natural flavonoid found in the roots of Lithospermum erythrorhizon, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of shikonin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Shikonin significantly relaxed fluoride-, thromboxane $A_2$- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, shikonin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and the inhibition of MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of shikonin on agonist-induced vascular contraction regardless of endothelial function.