건강인에서 알코올의 종류와 양에 따른 내피세포 기능의 변화

김정규 ( Jung Kyu Kim ),구훈섭 ( Hoon Sup Koo ),배장호 ( Jang Ho Bae ),김기영 ( Ki Young Kim ) 대한내과학회 2005 대한내과학회지 Vol.69 No.3

Background: It is not clear how much amount is favourable to coronary heart disease, although cardioprotective effects of red wine were reported. Furthermore, there is no report showing the effects of soju, the popular liqour in Korea on endothelial function. We performed this study to know early effects of alcohol on endothelial function in healthy subjects according to the kinds and the amounts of alcohol. Methods: Endothelial function was measured by using high-resolution ultrasound in 20 healthy subjects. Ten subjects were crossover studied according to the types of alcohol (120 cc of red wine and 45 cc of soju) and the other ten subjects were studied using the half dosage of the same alcohol. Results: The endothelial function can be impaired during 1 to 2 hours after alcohol ingestion (Soju 45 cc and red wine 120 cc, p<0.05), then recovered to baseline level. However, these impaired endothelial functions were associated with an increased brachial artery diameter. The endothelial function was recovered to baseline level more earlier in case of red wine than that of soju 2 hours vs 3 hours. Red wine 60cc and Soju 22.5 cc can improve the endothelial function in healthy subjects 2 and 3 hours after ingestion, respectively. These effects were not related with vasodilatory effects of alcohol. Conclusion: This study suggests that small amounts of alcohol can improve the endothelial function in healthy subjects independently with the vasodilatory effects of alcohol. The amounts of alcohol showing beneficial effects on endothelial function were lower than our expectation (a half cup). (Korean J Med 69:284-292, 2005)

Effects of exploration and molecular mechanism of CsV on eNOS and vascular endothelial functions

Zuo, Deyu,Jiang, Heng,Yi, Shixiong,Fu, Yang,Xie, Lei,Peng, Qifeng,Liu, Pei,Zhou, Jie,Li, Xunjia Techno-Press 2022 Advances in nano research Vol.12 No.5

This study aimed to investigate the effects and potential mechanisms of Chikusetsusaponin V (CsV) on endothelial nitric oxide synthase (eNOS) and vascular endothelial cell functions. Different concentrations of CsV were added to animal models, bovine aorta endothelial cells (BAECs) and human umbilical vein endothelial cells (HUVECs) cultured in vitro. qPCR, Western blotting (WB), and B ultrasound were performed to explore the effects of CsV on mouse endothelial cell functions, vascular stiffness and cellular eNOS mRNA, protein expression and NO release. Bioinformatics analysis, network pharmacology, molecular docking and protein mass spectrometry analysis were conducted to jointly predict the upstream transcription factors of eNOS. Furthermore, pulldown and ChIP and dual luciferase assays were employed for subsequent verification. At the presence or absence of CsV stimulation, either overexpression or knockdown of purine rich element binding protein A (PURA) was conducted, and PCR assay was employed to detect PURA and eNOS mRNA expressions, Western blot was used to detect PURA and eNOS protein expressions, cell NO release and serum NO levels. Tube formation experiment was conducted to detect the tube forming capability of HUVECs cells. The animal vasodilation function test detected the vasodilation functions. Ultrasonic detection was performed to determine the mouse aortic arch pulse wave velocity to identify aortic stiffness. CsV stimulus on bovine aortic cells revealed that CsV could upregulate eNOS protein levels in vascular endothelial cells in a concentration and time dependent manner. The expression levels of eNOS mRNA and phosphorylation sites Ser1177, Ser633 and Thr495 increased significantly after CsV stimulation. Meanwhile, CsV could also enhance the tube forming capability of HUVECs cells. Following the mice were gavaged using CsV, the eNOS protein level of mouse aortic endothelial cells was upregulated in a concentration- and time-dependent manner, and serum NO release and vasodilation ability were simultaneously elevated whereas arterial stiffness was alleviated. The pulldown, ChIP and dual luciferase assays demonstrated that PURA could bind to the eNOS promoter and facilitate the transcription of eNOS. Under the conditions of presence or absence of CsV stimulation, overexpression or knockdown of PURA indicated that the effect of CsV on vascular endothelial function and eNOS was weakened following PURA gene silence, whereas overexpression of PURA gene could enhance the effect of CsV upregulating eNOS expression. CsV could promote NO release from endothelial cells by upregulating the expression of PURA/eNOS pathway, improve endothelial cell functions, enhance vasodilation capability, and alleviate vessel stiffness. The present study plays a role in offering a theoretical basis for the development and application of CsV in vascular function improvement, and it also provides a more comprehensive understanding of the pharmacodynamics of CsV.

Flow-Mediated Vasodilation으로 평가한 일회 혈액투석 후 혈관내피세포 기능의 변화

임성우,신윤미,한정호,윤수인,권순길,김혜영 대한신장학회 2005 Kidney Research and Clinical Practice Vol.24 No.6

Background:The cardiovascular morbidity and mortality are much higher in the patients who undergo hemodialysis than normal population. Atherosclerotic vascular disease is one of the most important causes of cardiovascular disease, and it is thought to be related to endothelial function. It is known that endothelial function in the end-stage renal disease (ESRD) patients is decreased, but it is not clear the hemodialysis can improve the endothelial function or not. Hemodialysis can remove uremic toxins and improve endothelial function, but it also can cause oxidative stress to vascular endothelial cell. The purpose of this study is to determine whether hemodialysis could improve endothelial function compared with simple ultrafiltration in the same patient. Methods:We prospectively evaluated endothelial function of hemodialysis patients by flow-mediated vasodilation (FMD) method in the patient's right brachial artery. Total thirteen patients were enrolled in this study, and their right brachial artery diameters were measured by 7 MHz echocardiography probe, and calculated by enlarged scan image. FMD were measured before and after hemodialysis, and measured before and after simple ultrafiltration in the same patient, same four hours of each session. Results:The mean brachial artery diameters were 4.18±1.11 mm in pre-hemodialysis and 4.25±1.15 mm in pre-ultrafiltration respectively, and there was no statistic difference. Average percent change of brachial artery diameter before and after hemodialysis were 2.20±1.67 and 1.35±1.22% (p<0.05). The same of ultrafiltration were 2.13±1.99 and 2.72±1.79% (p=0.431). Conclusion:In summary, flow mediated vasodilation after a single session of hemodialysis, in contrast with simple ultrafiltration, could be diminished significantly. (Korean J Nephrol 2005;24(6):913-920) 배 경:투석을 받는 말기신부전 환자는 죽상경화증으로 인한 심혈관계 사망률이 유의하게 증가되어 있다. 이러한 죽상경화증의 원인 중 하나로 생각되는 것이 혈관내피세포 기능의 저하이다. 혈관내피세포 기능이 투석에 의한 요독소 감소, 산화 스트레스, 그리고 투석간 혈장량 변화 등과 관련이 있을 것으로 생각되어 혈액투석과 한외여과에서 혈관내피세포 기능을 비교해보기로 하였다. 방 법:13명의 말기신부전 환자에게서 혈액투석 전후 및 한외여과 전후에 비동정맥루 팔의 상완동맥에서 7 MHz 고해상도 혈관초음파 탐촉자를 이용하여 혈관내피세포 의존성 혈관 이완능 (flow-mediated vasodilation, endothelium dependent vasodilation:FMD)을 측정하여 비교하였다. 결 과:투석 전후 BUN과 크레아티닌은 48.3±17.4 mg/dL, 7.3±3.7 mg/dL 및 24.4±12.5 mg/dL, 3.6±1.6 mg/dL이었고 (p<0.05), 한외여과 전후 BUN과 크레아티닌은 48.2±14.0 mg/dL, 7.2±3.1 mg/dL 및 48.4±17.4 mg/dL, 7.1±3.1 mg/dL이었다 (p=0.889, p=0.498). 투석 전후 호모시스테인 값은 19.0±3.8 µmol/L, 15.6±4.9 µmol/L이었고 (p<0.05), 한외여과 전후에는 21.4±6.3 µmol/L, 22.1±10.5 µmol/L이었다 (p=0.745). 투석 전후 malondialdehyde (MDA)는 4.5±1.1 µmol/L, 3.9±1.5 µmol/L이었고 (p<0.05), 한외여과 전후에는 4.5±1.6 µmol/L, 4.8±2.5 µmol/L이었다 (p=0.533). 투석 전과 한외여과 전 상완동맥의 평균 내경직경 기저치는 4.18±1.11 mm 및 4.25±1.15 mm이었으나 투석 전후 상완동맥 내경직경의 평균 변화량은 2.20±1.67%, 1.35±1.22% (p<0.05), 그리고 한외여과 전후 평균 변화량은 2.13±1.99%, 2.72±1.79%이었다 (p=0.431). 혈액투석과 반대로 한외여과 후에는 체중감소량이 클수록 혈관이완능이 감소하는 경향을 보였다 (p<0.05, r=-0.827). 결 론:말기신부전 환자에서 단일 혈액투석 후 측정한 내피세포 의존성 혈관 확장 반응은 한외여과 후와는 달리 감소되어 나타날 수 있다고 생각된다.

The effect of antiplatelet drug on coronary endothelial and microvascular function: comparison with ticagrelor and clopidogrel

( Woong Gil Choi ),( Gi Chang Kim ),( Cheol Ho Lee ),( Hye Young Kim ),( Dong Woon Kim ) 대한내과학회 2021 The Korean Journal of Internal Medicine Vol.36 No.2

Background/Aims: Coronary endothelial and microvascular function play important roles in cardiovascular disease. We aimed to evaluate the effect of ticagrelor on coronary artery function and tested the antiplatelet effect of low dose ticagrelor in East-Asian patients. Methods: Sixty-one consecutive patients with non-significant coronary disease were included in the study. Initially, patients were randomized in 1:1:1 ratio to receive drugs: ticagrelor 90 mg twice a day (bid; n = 22), ticagrelor 45 mg bid (n = 19) or clopidogrel 75 mg once a day (qd; n = 20) and then divided into two groups (ticagrelor vs clopidogrel) for evaluation of coronary artery function, and three groups for evaluation of antiplatelet function. Endothelial dysfunction was measured by coronary flow reserve (CFR), and changes in the levels of asymmetric dimethylarginine (ADMA), cluster of differentiation (CD) 40 ligand, and P-selectin. Microvascular function was evaluated as index of microvascular resistance (IMR). Platelet reactivity was assessed by VerifyNow P2Y12 assay. Results: The levels of CFR, ADMA, and CD 40 ligand were not different between the two groups. However, P-selectin was lower in the ticagrelor group compared with clopidogrel group. IMR was significantly lower in the ticagrelor group compared with clopidogrel group (median, 15.0 [interquartile range, 12.0 to 21.0] vs. 47.5 [23.0 to 67.5], p = 0.014). There was significant difference in platelet inhibition among the three groups (ticagrelor 90 mg bid vs. ticagrelor 45 mg bid vs. clopidogrel 75 mg qd; 85.57 ± 47.63 vs. 120.33 ± 51.09 vs. 256.42 ± 55.10, p < 0.001) Conclusions: It is hypothesized that ticagrelor might ameliorate the coronary microvascular function. When compared with clopidogrel, low dose ticagrelor exhibited satisfactory antiplatelet effect in the present study.

Exercise-Induced Laminar Blood Flow Maintains Vascular Function by Enhanced Endothelial Homeostasis

김지석,백경완,김소정,이정훈,Craig A Johnston,박윤정 한국운동생리학회 2024 운동과학 Vol.33 No.2

PURPOSE: Laminar blood flow is known to play a critical role in maintaining endothelial homeostasis in blood vessels. It exerts a shear stress on the endothelial cells (ECs), which is essential for the regulation of various vascular functions. In this study, the effects of laminar blood flow-induced enhanced endothelial homeostasis on the maintenance of vascular function were investigated. METHODS: Human umbilical vein endothelial cells (HUVECs) were employed to study gene expression associated with vessel dilation and angiogenesis in response to varying shear stress levels. To assess angiogenesis, experimental mice participated in voluntary wheel running for 16 weeks. To evaluate the vascular autophagic function, the six weeks old C57BL/6 mice underwent an hour of forced treadmill running for 10 weeks. The resulting gene expression was evaluated through western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Disturbed flow resulting from partial ligation surgery in the mice’s carotid artery led to a decrease in angiogenic capacity compared to the laminar flow observed in ex vivo sprouting assays. Cultured HUVECs exhibited a significant increase in VEGF expression when exposed to increased durations of 20 dyne/cm² laminar shear stress (LSS). Following a 10-week treadmill exercise regimen, ECs in the carotid arteries of mice showed a significant increase in the expression of autophagic genes, such as LC3II, Atg3, and Atg7, which was not observed in smooth muscle cells (SMCs). LSS was found to boost the expression of both total and phosphorylated eNOS, genes involved in vascular dilation regulation, specifically in ECs. CONCLUSIONS: These findings suggest that laminar blood flow sustains vascular function, such as angiogenic capacity, through the enhancement of endothelial homeostasis.

Effects of interval training on blood pressure and endothelial function in hypertensive patients

( Eun-ah Jo ),( Kyoung-im Cho ),( Do-sun Lim ),( Ji-hyun Choi ),( Jung-jun Park ) 한국스포츠과학원 2018 International Journal of Applied Sports Sciences Vol.30 No.1

Background: Several studies have recently shown that high-intensity interval training (HIIT) is superior to moderate-intensity continuous exercise (MICE) for improvements on endothelial in patients with cardiovascular disease. However, little is known about its effects on changes in blood pressure, especially in hypertensive patients. Purpose: To compare the effects of HIIT and MICE on changes in blood pressure reduction and endothelial function in hypertensive patients. Methods: Fourteen hypertensive patients, aged 52.1±7.6, participated in this study. They tapered off their medications, if necessary, and were randomized to either HIIT (n = 7) or CME (n = 7) group. HIIT was composed of 5 sets of 3 min exercise at 80% HRR, and each interval was separated by 3 min recovery at 40% HRR. MICE was composed of 35 min exercise at 60% HRR. Both groups were designed to use same energy expenditure, and performed exercise 5 days/week for 4 weeks. Endothelial function was determined by assessing endothelial progenitor cells (EPCs) using flow cytometry and flow mediated dilation (FMD) using ultrasonography. Blood pressure (BP) and heart rate (HR) were measured at rest by using automatic blood pressure monitor. Repeated ANOVA was performed to analyze if the changes in dependent variables after training are different between HITT and MICE group. Statistical significance was at p< .05. Results: There was a significant interaction in resting HR, but not in BP, FMD, and EPCs between groups after training. Systolic BP was significantly decreased in both HITT group (p = .012) and MICE group (p = .048) after training. However, diastolic BP and FMD was significantly decreased (p = .021) and increased (p = .049) in only HIIT group, respectively. EPCs were not significantly changed after training in both HIIT and MICE group. Conclusion: The results of this study indicate that there is no big difference in HIIT and MICE for BP reduction, and HIIT and MICE are both effective for BP reduction in hypertensive patients. However, further researches are needed to illuminate differential effects of HIIT and MICE on BP response and endothelial function.

Buddhist meditation for vascular function: a narrative review

Anjalee Thanuja Amarasekera,Dennis Chang 한국한의학연구원 2019 Integrative Medicine Research Vol.8 No.4

Background: High blood pressure represents an important risk factor for diseases related to cardiovascular system and is directly associated with high oxidative stress, inflammation and vascular endothelial dysfunction. Recently, there is promising data available to suggest that meditation-based low-cost and low-risk lifestyle modification strategies may provide beneficial effects on chronic inflammation, oxidative stress and maintenance of blood pressure, both in young and older adults. This review aims to summarize the evidence regarding the effectiveness of Buddhist meditation for vascular endothelial function and blood pressure. Method: A search was conducted using Ovid MEDLINE, Scopus, CINAHL and PsycINFO for articles published from 1990 to 2018. Results: Relevant articles (n = 407) were reviewed and 5 met selection criteria. Several lines of studies have provided compelling data showing that Buddhist meditation approach was effective in improving inflammation and vascular function (endothelial vasodilation and arterial stiffness) in both young and elderly cohorts. Particularly, Buddhist meditation approach has shown to be effective in reducing plasma inflammatory markers, increasing nitric oxide concentration and improving vascular endothelial function and glycemic control, which in turn can be favorable factors for demonstrated positive effects of Buddhist meditation on blood pressure and vascular function. Conclusion: This paper presents brief overview of clinical outcomes of complementary therapeutic approach of Buddhist meditation in vascular function. In future, well-structured systematic reviews are essential to report specificity of Buddhist mindfulness-based approach on vascular function, blood pressure and other cardiovascular risk factors.

Effects of lycopene supplementation on oxidative stress and markers of endothelial function in healthy men

Kim, J.Y.,Paik, J.K.,Kim, O.Y.,Park, H.W.,Lee, J.H.,Jang, Y.,Lee, J.H. Elsevier Scientific Publ. Co 2011 Atherosclerosis Vol.215 No.1

Objective: The objective was to determine the effects of lycopene supplementation on endothelial function assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) and oxidative stress. Methods: Healthy men (n=126) were randomized to receive placebo (n=38), 6mg (n=41), or 15mg (n=37) lycopene daily for 8-week. Results: Serum lycopene increased in a dose-dependent manner after 8-week supplementation (P<0.001). The 15mg/day group had greater increase in plasma SOD activity (P=0.014) and reduction in lymphocyte DNA comet tail length (P=0.042) than the placebo group. Intragroup comparison revealed a 23% increase in RH-PAT index from baseline (1.45+/-0.09 vs. 1.79+/-0.12; P=0.032) in the 15mg/day group after 8-week. hs-CRP, systolic blood pressure, sICAM-1 and sVCAM-1 significantly decreased, and β-carotene and LDL-particle size significantly increased only in the 15mg/day group. Interestingly, the beneficial effect of lycopene supplementation on endothelial function (i.e., RH-PAT and sVCAM-1) were remarkable in subjects with relatively impaired endothelial cell function at initial level. Changes in RH-PAT index correlated with SOD activity (r=0.234, P=0.017) especially in the 15mg lycopene/day group (r=0.485, P=0.003), lymphocyte DNA comet tail moment (r=-0.318, P=0.001), and hs-CRP (r=-0.238, P=0.011). In addition, changes in lycopene correlated with hs-CRP (r=-0.230, P=0.016) and SOD activity (r=0.205, P=0.037). Conclusion: An increase in serum lycopene after supplementation can reduce oxidative stress which may play a role in endothelial function.

저농도 및 고농도의 알코올의 투여와 혈관수축성의 조절

제현동(Hyun Dong Je) 대한약학회 2012 약학회지 Vol.56 No.3

The aim of present study was to investigate the possible influence and related mechanism of alcohol on the arterial contraction. Vascular contraction involves the activation of thick or thin filament pathway. However, there are no reports addressing the question whether this pathway is involved in alcohol-induced regulation. We hypothesized that alcohol plays a role in vascular contraction evoked by a vasoconstrictor in rat aortae regardless of endothelial function. Denuded arterial rings from male rats were used and isometric contractions were recorded using a computerized data acquisition system. Interestingly, alcohol at a low concentration (3% v/v) inhibited thromboxane A2 or phorbol ester-induced contraction with endothelial function but at a high concentration (10%) didn't inhibit and rather increased the contraction in the denuded muscle. Therefore, alcohol at a low concentration decreases the contraction and alcohol at a high concentration increases the contraction suggesting that additional pathways different from endothelial nitric oxide synthesis might be involved in the regulation of contractility. In conclusion, alcohol has some effect on the regulation of contractility regardless of endothelial function.

규칙적인 운동을 통한 심폐체력의 향상이 비만 청소년의 혈관기능에 미치는 영향

박수현 ( S. H Park ),윤은선 ( E. S Yoon ),제세영 ( S. Y Jae ) 한국운동생리학회 2012 운동과학 Vol.21 No.4

Vascular endothelial dysfunction and increased arterial stiffness are associated with early atherosclerosis in obese adolescents. High cardiorespiratory fitness (CRF) is associated with diminished cardiovascular risk factors and improved vascular endothelial function in children. The purpose of the study was to examine effects of the improvement of cardiorespiratory fitness by regular exercise training on vascular function in obese adolescents. Twenty one obese adolescents (Schoolboy, Mean age:13-14 yr) were randomly assigned to an exercise training (ET)(12 weeks, 40 minutes, 5 days/week) group (n=11) and a non exercise control (CON) group (n=10). Cardiorespiratory fitness was measured using maximal oxygen uptake with metabolic gas analysis and body composition was determined by bioelectrical impedance. We measured carotid-femoral pulse wave velocity and reactive hyperemia index as indices of vascular function. Waist girth was significantly decreased in ET group than in CON group (ET 94.41±6.17 to 92.62±6.13 vs. CON 92.62±7.80 to 94.27±9.23 ㎝, p <.05). Cardiorespiratory fitness was significantly increased in ET group than CON group(ET 32.35±6.49 to 39.24±6.63 vs. CON 34.59±5.47 to 38.36±6.54 ㎖/㎏/min, p <.05). Body mass index and selected CVD risk factors were not improved in ET group. Reactive hyperemia index was significantly increased in ET group (ET 1.60±0.45 to 1.87±0.58 vs. CON 1.73±0.39to 1.43±0.26%, p =<.05) but carotid-femoral pulse wave velocity did not significantly decrease in ET group (ET 5.77±5.40 to 5.40±0.53 vs. CON 5.12±0.53 to 5.05±0.54 m/s, NS). Change in cardiorespiratory fitness was associated with change in reactive hyperemia index after adjusted for changes in waist (r=.457, p <.037). These results show that regular exercise training improved endothelial function, and this was associated with improved cardiorespiratory fitness independent of changes in body weight in obese adolescents.