• Title/Summary/Keyword: Endothelium function

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Lymphoid Lineage γδ T Cells Were Successfully Generated from Human Pluripotent Stem Cells via Hemogenic Endothelium

  • Soo-Been Jeon; A-Reum Han;Yoo Bin Choi;Ah Reum Lee;Ji Yoon Lee
    • International Journal of Stem Cells
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    • v.16 no.1
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    • pp.108-116
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    • 2023
  • γδ T cells are a rare and unique prototype of T cells that share properties with natural killer cells in secondary lymphoid organs. Although many studies have revealed the function and importance of adult-derived γδ T cells in cancer biology and regenerative medicine, the low numbers of these cells hamper their application as therapeutic cell sources in the clinic. To solve this problem, pluripotent stem cell-derived γδ T cells are considered alternative cell sources; however, few studies have reported the generation of human pluripotent stem cell-derived γδ T cells. In the present study, we investigated whether lymphoid lineage γδ T cells were successfully generated from human pluripotent stem cells via hemogenic endothelium under defined culture conditions. Our results revealed that pluripotent stem cells successfully generated γδ T cells with an overall increase in transcriptional activity of lymphoid lineage genes and cytolytic factors, indicating the importance of the optimization of culture conditions in generating lymphoid lineage γδ T cells. We uncovered an initial step in differentiating γδ T cells that could be applied to basic and translational investigations in the field of cancer biology. Based on our result, we will develop an appropriate method to purify γδ T cells with functionality and it helpful for the study of basic mechanism of γδ T cells in pathophysiologic condition as well as clinic application.

Pharmacological Actions of Ginseng -The endothelium related response (인삼의 약리작용 - 내피와 관련하여 -)

  • 김낙두;강수연
    • Journal of Ginseng Research
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    • v.20 no.4
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    • pp.416-430
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    • 1996
  • With the progress of chemical researches in ginseng studies, efforts to elucidate the pharmacological actions of ginseng have been greatly increased. The majority of ginseng reaserches in the past has been performed with crude extracts from ginseng roots to verify scientifically the empirical application of ginseng in men and animals recently. Ginseng reaserches have been done mostly with pure ginsenosides and there has been a shift in focus to the various biochemical pathways. It was demonstvated that ginseng had diverse effects by modulating the second-messenger system, such as cyclic nucleotides. calcium The demonstration in 1987 of the formation of nitric oxide(NO, endothelium-derlled rectating factor) by an enzyme in vascular endothelial cells opened up a new area of biological reaserches of ginseng. It was shown that vascular relaxations induced by glnsenosides are mediated by release of nitric oxide from endothelial cells. According to the literature search from'hledline". There have been 737 original and review articles during the last 30 years. In these review articles, an attempt has been made to summalize some results from some of these published papers. Ginseng has a wide range of phal.macologtcal and therapeutical actions. It acts on the centralral nervous system and cardiovascular system, promotes immune function and metabolism. Possesses anti-stress. Anti-cancer and anti-ageing activities, and so on.o on.

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Studies of Evodiae Fructus on the blood pressure in spontaneously hypertensive rats (오수유(吳茱萸)가 선천성고혈압(先天性高血壓)흰쥐의 혈압(血壓)에 미치는 영향(影響))

  • Kang, Sin-In;Kim, Ho-Cheol;Rheu, Hang-Mook;Yang, Ji-Seon;Jung, Soo-Yeon
    • The Journal of Korean Medicine
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    • v.19 no.2
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    • pp.50-58
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    • 1998
  • The effects of the Evodiae fructus on the cardiovascular function were assessed in spontaneously hypertensive rats, and isolated preparation of spontaneously hypertensive rats aortic strip. In spontaneously hypertensive rats, intraperitoneal administration of methanol crude extract of Evodiae Fructus (0.5mg/kg) lowered aterial blood pressure which lasted for at least 4 hours. The hypotensive effect of Evodiae Fructus was more stronger with ${\alpha}-adrenoreceptor$ inhibitor(Phentholamine) and it was not affected by ${\beta}-adrenoreceptor$ inhibitor(Propranolol). The hypotensive effect of Evodiae Fructus was abolished by NAME. It is suggested that the hypotensive effect of Evodiae Fructus may be concern with endothelium-derived relaxing factor and it may be mediated through NO synthesis. Evodiae Fructus showed a vasorelaxing effect on denude aortic strip. It is suggested that Evodiae Fructus has a direct relaxing effect on vascular smooth muscle cells. Judging from above results, it was proved that hypotensive effect of Evodiae Fructus. The mechanism of hypotensive action may be concern with endothelium-derived relaxing factor and direct relaxing effect on vascular smooth muscle cells. Therefore, it is suggested that Evodiae Fructus is applicable to hypertension.

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Characterization of $ET_B$ Receptor-mediated Relaxation in Precontracted Mesenteric Artery from Streptozotocin-induced Diabetic Rats

  • Eom, Yang-Ki;Kim, Koan-Hoi;Rhim, Byung-Yong
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.5
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    • pp.305-314
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    • 2005
  • Diabetes mellitus is associated with vascular complications, including an impairment of vascular function and alterations in the reactivity of blood vessels to vasoactive substances in various vasculature. In the present study, the authors have observed endothelin-B ($ET_B$) receptor agonist-induced relaxation in precontracted mesenteric arterial segments from streptozotocin (STZ)-induced diabetic rats, which was not shown from control rats or in other arterial segments from diabetic rats. Accordingly, the goal of this study was to investigate in what way STZ-induced diabetes altered reactivity of the mesenteric arterial bed and to examine the causal relaxation, if any, between this $ET_B$ receptor-mediated relaxation and endothelial paracrine function, especially nitric oxide (NO) production. The relaxation induced by $ET_B$ agonists was not observed in mesenteric arteries without endothelium. The relaxation to $ET_B$ agonists was completely abolished by pretreatment with BQ788, but not by BQ610. $N_{\omega}-nitro-L-arginine$ methyl ester and soluble guanylate cyclase inhibitors, methylene blue or LY83583 significantly attenuated the relaxant responses to $ET_B$ agonists, respectively. When the expression of eNOS and iNOS was evaluated on agarose gel stained with ethidium bromide, the expression of eNOS mRNA in diabetic rats was significantly decreased, but the expression of iNOS was increased compared with control rats. Furthermore, the iNOS-like immunostaining was densely detected in the endothelium and slightly in the arterial smooth muscle of diabetic rats, but not in control rats. These observations suggest that $ET_B$ receptor may not play a role in maintaining mesenteric vascular tone in normal situation. However, the alterations in $ET_B$ receptor sensitivity were found in diabetic rats and lead to the $ET_B$ agonist-induced vasorelaxation, which is closely related to NO production. In the state of increased vascular resistance of diabetic mesenteric vascular bed, enhanced NO production by activation of iNOS could lead to compensatory vasorelaxation to modulate adequate perfusion pressure to splanchnic area.

The Effect of High Fat Diet on the Vasoendothelial Cell in Healthy Adults

  • Choi Sun-Young;Kim Jai-Young
    • Biomedical Science Letters
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    • v.11 no.1
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    • pp.79-84
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    • 2005
  • This study was performed to determine whether postprandial hypertriglyceridemia can affect the endothelial function. Endothelial function was assessed by flow-mediated endothelium-dependent brachial artery vasodilation (FMD) which was defined as percentile changes of diameter. Thirty one patients were enrolled in this study. The serum lipid profiles and FMD were measured at fasting, and after low fat and high fat meals. The serum triglycerides at 2 hours after a high fat meal were significantly increased compared to those measured at 2 hours after a low-fat meal and at fasting state (P<0.05). The FMD was transiently decreased (P<0.0001) from $11.4{\pm}3.2\%$ at fasting state to $6.5{\pm}2.5\%$ after a high-fat meal. The FMD was inversely related with postprandial hypertriglyceridemia (P<0.05). In conclusion, this study may suggest that postprandial hypertriglyceridemia causes endothelial dysfunction.

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Effect of Dietary Fat Sources and L-arginine Supplementation on Endothelial function and Lipid Metabolism in Streptozotocin-Induced Diabetic Rats (식이지방의 종류와 L-arginine 보충이 당뇨쥐의 ENdothelium 기능 및 체내 지질대사에 미치는 영향)

  • 장문정;김연중;김명환
    • Journal of Nutrition and Health
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    • v.35 no.1
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    • pp.5-14
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    • 2002
  • Alteration in the syntesis or enhanced inactivation of nitric oxide(NO) can induce impairment of endothelial cell function. Insulin dependent diabetes mellitus(IDDM) is characterized by impaired endothelial function and vascular disease. NO is produced through L-arginine pathway To elucidate the hypothesis that the decreased production on NO in IDDM reflects vascular damage and the NO production can be manipulated by either dietary fat(7% of kg diet) or the oral supplementation with L-arginine(2g/kg bw), plasma markers for vascular endothelial damage and plasma lipid profiles were measured in streptozotocin(STZ)-induced diabetic rats. Diabetic or normal Sprague-Dawley rats were fed 6 different experimental diets for 4 weeks(SO : soybean oil, SOA: soybean oil + L-arginine supplementation, BT : beef tallow, BTA_ beef tallow + L-arginine supplementation, OV olive oil, OVA : olive oil + L-arginine supplementation). Plasma glucose, total cholesterel, HDL-cholesterol, LDL-cholesterol and triglyceride were measured. Endothelial markers, plasma von Willebrand factor(vWf), thromboxane B$_2$, and 6-keto PGF1$\alpha$ of aorta were measured by ELISA. Plasma NO production was evaluated through the measurement of nitrite by EIA. Feeding saturated fatty acid(SFA, BT) increased relative liver size(RLS) in diabetic rats compared to either polyunsatunted fatty acid(PUFA, SO) or monounsaturated fatty acid(MUFA, OV) The supplementation of L-arginine inhibited the liver and kidney enlargement in olive oil find diabetic rats. Plasma glucose was lower in diabetic animal find the olive oil compared to fed beef tallow and the supplementation L-arginine decreased it in diabetic rats find beef tallow significantly(p < 0.05). Plasma TXB$_2$ levels were increased due to diabetes and the value of beef tallow group showed highest value. Plasma vWf concentration of beef tallow group was higher value in normal rats and was elevated more in diabetes. In diabetic groups, the vWf concentration of olive oil group was lower than beef tallow or soybean oil group. The supplementation of L-arginine in diabetic rats decreased plasma TXB$_2$ and vWf levels significantly(p < 0.05). NO production was higher in normal olive oil fed rats and was tend to be decreased in diabetic rats and the supplementation of L-arginine recovered to normal value(p < 0.05), Olive oil supplemented with L-arginine tended to lower plasma total cholesterol and LDL-cholesterol after 4 week treatment. These results suggest that generalized vascular endothelial changes based on plasma TXB$_2$and vWf occurs in diabetic rats. and olive oil with L-arginine supplementation contributes to a better control of the hyperglycemia, endothelial changes and hypercholesterolemia accompanying diabetes as compared with beef tallow or soy bean oil in this rat model.

Effects of a Smoking Cessation Education on Smoking Cessation, Endothelial Function, and Serum Carboxyhemoglobin in Male Patients with Variant Angina (금연교육이 이형 협심증 남성 흡연 환자의 금연, 혈관내피세포 기능 및 혈청 일산화탄소헤모글로빈에 미치는 효과)

  • Cho, Sook-Hee
    • Journal of Korean Academy of Nursing
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    • v.42 no.2
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    • pp.190-198
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    • 2012
  • Purpose: The aim of this study was to evaluate the effects of a smoking cessation education on endothelial function and carboxyhemoglobin levels in smokers with variant angina. Methods: A nonequivalent control group pretest-posttest design was used. Participants were 60 male smokers with variant angina admitted to one hospital: the control group (30) between September and December, 2009, and the experimental group (30) between February and May, 2010. Endothelial function, as defined by flow-mediated vasodilation (FMD) of the brachial artery, and serum carboxyhemoglobin (COHb) were determined at baseline and at 3 months after the initiation of education in both groups. Results: Three months after the program, smoking cessation was successful in 22 of the 30 smokers in the experimental group, but only in 4 of 30 smokers in the control group ($p$<.001). After the education, the experimental group showed a significant increase in FMD, and a significant decreased in serum COHb compared with the control group. Conclusion: The findings indicate that this smoking cessation education program is effective for hospitalized smokers with variant angina.

The Effect of Resveratrol on U-46619 (High Concentration)-induced Vasoconstriction Regulating MEK or Rho-kinase Activity (고농도 U-46619에 의한 혈관의 수축에 대한 Resveratrol의 억제 작용에서 MEK 활성 또는 Rho-kinase 활성의 변화: 내피 비의존적 수축성 조절)

  • Je, Hyun-Dong
    • YAKHAK HOEJI
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    • v.55 no.2
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    • pp.138-144
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    • 2011
  • The aim of present study was to investigate the possible influence and related mechanism of resveratrol on U-46619 (high concentration)-induced vasoconstriction. Agonist-induced vascular smooth muscle contractions involve the activation of thick or thin filament pathway. However, there are no reports addressing the question whether this pathway is involved in resveratrol-induced relaxation in rat aortae contracted with high U-46619. We hypothesized that MEK or Rho-kinase inhibition plays a role in vascular relaxation evoked by resveratrol in rat aortae. Endothelium-denuded arterial rings from male Sprague-Dawley rats were used and isometric contractions were recorded using a computerized data acquisition system. Resveratrol fully inhibited U-46619 in low concentration-induced contraction regardless of endothelial function. However, resveratrol partially decreased U-46619 in high concentration-induced contraction regardless of endothelial function. Interestingly, only in U-46619 (high concentration)-induced contraction, no significant decrease was observed in phospho-ERK1/2 levels and slight decrease in phospho-MYPT1 levels suggesting that additional pathways different from them or endothelial nitric oxide synthesis might be involved in the vasorelaxation. In conclusion, in high U-46619-contracted rat aortae, resveratrol showed relaxation response regardless of endothelial function significantly but slightly decreasing MYPT1 phosphorylation rather than ERK1/2 phosphorylation.

Regulatory Effect of Spray-Dried Lactiplantibacillus plantarum K79 on the Activation of Vasodilatory Factors and Inflammatory Responses

  • Ki Hwan Kim;Yongjin Hwang;Seok-Seong Kang
    • Food Science of Animal Resources
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    • v.44 no.1
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    • pp.216-224
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    • 2024
  • The reduction of nitric oxide (NO) bioavailability in the endothelium induces endothelial dysfunction, contributing to the development of hypertension. Although Lactobacillus consumption decreases blood pressure, intracellular signaling pathways related to hypertension have not been well elucidated. Thus, this study examined the effect of spray-dried Lactiplantibacillus plantarum K79 (LpK79) on NO production, intracellular signaling pathways, and inflammatory responses related to vascular function and hypertension. NO production was assessed in human umbilical vein endothelial cells (HUVECs) treated with LpK79. Endothelial NO synthase (eNOS) and intracellular signaling molecules were determined using Western blot analysis. LpK79 dose-dependently increased NO production and activated eNOS via the phosphoinositide 3-kinase/Akt signaling pathway HUVECs. Moreover, LpK79 mitigated the activation of crucial factors pivotal for vascular contraction in smooth muscle cells, such as phospholipase Cγ, myosin phosphatase target subunit 1, and Rho-associated kinase 2. When HUVECs were treated with LpL79 in the presence of Escherichia coli lipopolysaccharide (LPS), LpK79 effectively suppressed mRNA and protein expression of pro-inflammatory mediators induced by E. coli LPS. These results suggest that LpK79 provided a beneficial effect on the regulation of vascular endothelial function.

Electrical Stimulation Causes Endothelium-Dependent Relaxation in Isolated Aortic Vessels of the Rabbit (토끼 흉부 대동맥 절편의 전기자극에 대한 수축 및 이완반응)

  • Lee, Seok-Gi;Choe, Hyeong-Ho;Lee, Jong-Un
    • Journal of Chest Surgery
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    • v.28 no.8
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    • pp.742-746
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    • 1995
  • The present study was aimed at investigating possible transmitter mechanisms in the endothelial cell layer in regulating the tone of the vascular smooth muscle. The thoracic aorta was isolated from the anesthetized male white rabbits and its helical strips were prepared. Electrical field stimulation was delivered to platinum wire electrodes positioned parallel to the vessel segment preconstricted with phenylephrine [3.5x10-6 mol/L at a distance of 1.5-2.0 mm. The electrical stimulation [70 V, 5 msec, 0.5-200 Hz caused either relaxation only [34% or a biphasic response [prolonged relaxation following a weak and transient contraction, 66% . The relaxation response was frequency- dependent, and at 200 Hz a complete relaxation was noted. Mechanical rubbing of the endothelial layer abolished or greatly attenuated the relaxation. The relaxation was also markedly attenuated in the presence of NG-nitro- L-arginine methyl ester [10-3mol/L or procaine hydrochloride [3.5x10-4mol/L . Tetrodotoxin,guanethidine, atropine or indomethacin failed to block or enhance the relaxation response to electrical field stimulation. It is concluded that the vascular endothelium in the aorta contains diffusible substances that regulates the function of the smooth muscle layer, in which relaxation is more prominent than contraction. Their release by the electrical stimualtion in vitro may not involve classic neuronal transmitter release mechanisms or metabolism of arachidonic acids by cyclooxygenase. The release of the relaxing agents may require an increase in cytosolic calcium level. The chemical nature of the relaxant may be, to a large extent, nitric oxide.

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