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

목적: 적절한 음주는 심혈관계 위험을 낮추고, 내피 세포 기능 호전을 보여준다는 보고가 있다. 저자 등은 알코올의 종류와 양에 따라 건강한 정상 성인의 내피세포 기능에 미치는 알코올의 급성 효과를 알아 보고자 이 연구를 시행하였다. 방법: 20명(평균 연령; 25세)의 동맥경화 위험 인자가 없는 건강한 남자 의과 대학생을 대상으로 하였다. 내피 세포 기능 측정은 고해상도 초음파도를 사용하여 혈류 의존성 상완동맥 혈관확장능(FMD)으로 측정 하였다. 모든 피검자들은 공복 상태에서 오전 8시에 검사를 시행하였고, 검사 시작 전 혈압, 맥박, 혈중 콜레스테롤 농도, 중성지방농도, 혈당, FMD를 측정하였다. 피검자를 10명씩 2군으로 나눈 후 10명은 소주 45 cc (alcohol 11.3gm) 혹은 적포도주 120 cc (alcohol 14.5gm)를 마시게 한 후 음주 1, 2, 3, 4, 5시간째 FMD 측정을 반복하였다. 적포도주와 소주를 이용한 교차실험을 3일 간격으로 10명 모두에서 두 번 시행하였다. 다른 10명의 피검자는 소주 22.5 cc와 적포도주 60 cc를 이용하여 상기와 같은 검사를 반복하였다. 결과: 소주 45 cc와 적포도주 120 cc를 마신 군에서는 1시간과 2시간째 FMD의 유의한 감소를 보였으나(10.5% vs. 4.9% and 6.0%, 9.2% vs. 5.4% and 5.8%, respectively), 이는 알코올로 인한 혈관 확장 효과 때문이었다. 반면, 적포도주 60 cc를 마신 경우에는 2시간째 FMD가 호전되었고(7.6% vs. 8.8%, p=0.072), 소주 22.5 cc를 마신 경우에는 3시간째 FMD가 호전되었으며(7.6% vs. 9.0%, p=0.078), 이때 보인 내피세포 기능의 호전은 상완동맥 내경의 변화와도 상관이 없었다. 결론: 건강 성인에서 내피세포 기능 호전을 보이는 알코올의 양은 적포도주 반잔(60 cc)이었으며, 소주도 반잔(22.5 cc)을 마신 경우 내피 세포의 호전을 보였으며 이것은 일반적인 생각보다는 적은 양임을 알 수 있었다. 향후 알코올의 내피세포 기능 호전에 대한 기전에 대한 연구 결과와 장기 효과에 대한 연구가 필요할 것으로 보인다. 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.

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.

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 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 ) 한국스포츠정책과학원(구 한국스포츠개발원) 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.

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.

Curcumin supplementation attenuates the decrease in endothelial function following eccentric exercise

최영주,Yoko Tanabe,Nobuhiko Akazawa,Asako Zempo-Miyaki,Seiji Maeda 한국운동영양학회 2019 Physical Activity and Nutrition (Phys Act Nutr) Vol.23 No.2

[Purpose] Eccentric exercise induces a decrease in vascular endothelial function. Curcumin, a major component of turmeric, has potent antioxidant and anti-inflammatory properties that are associated with vascular protective effects. The present study examined the effect of acute supplementation of curcumin on eccentric exercise-induced endothelial dysfunction in healthy young men. [Methods] Fourteen healthy sedentary young men (range, 21–29 years) were assigned to either the curcumin (n = 6) or placebo (n = 8) group. All subjects consumed either curcumin or placebo before exercise, and eccentric exercise of the elbow flexors was performed with their nondominant arm. Before and 60 min after exercise, brachial artery flow-mediated dilation (FMD), as an indicator of endothelial function, was measured in the non-exercised arm. [Results] Brachial artery FMD significantly decreased following eccentric exercise (p < 0.05) in the placebo group, but acute supplementation with curcumin before exercise nullified this change. The change in FMD before and after eccentric exercise between the placebo and curcumin groups was significantly different (p < 0.05). [Conclusion] The present study found that acute curcumin supplementation could attenuate the decrease in endothelial function, as measured by FMD, following eccentric exercise in healthy young men.

Eicosapentaenoic Acid and Docosahexaenoic Acid in Endurance Performance and Cardiovascular Function

( Eisuke Ochi ),( Yosuke Tsuchiya ) 한국운동생리학회(구 한국운동과학회) 2019 운동과학 Vol.28 No.4

Fish oil contains omega-3 fatty acids, such as eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3). Consumption of EPA and DHA has been expected to improve fatigue recovery, endurance performance, antioxidant production, and anti-inflammatory responses. Therefore, this review aimed to evaluate the effects of omega-3 fatty acid on endurance performance as evaluated by human and animal studies and summarizes its effects on cardiovascular and endothelial functions. METHODS: This review summarized the effects of EPA and DHA supplementation on the maximum oxygen uptake, exercise economy, muscle endurance performance, and cardiovascular and endothelial functions. RESULTS: Effects of EPA and DHA supplementation on the maximum oxygen uptake are controversial. However, it has been suggested to improve the exercise economy and make the continuation of exercise easier. EPA and DHA supplementation could also improve endurance performance in the peripheral muscles. In addition, they may improve cardiovascular and vascular endothelial functions at rest and have positive effects on the heart rate, stroke volume, and cardiac output during a submaximal exercise. CONCLUSIONS: This review concluded that EPA and DHA are considered effective in improving endurance performance in the peripheral muscles and cardiovascular function.

규칙적인 운동을 통한 심폐체력의 향상이 비만 청소년의 혈관기능에 미치는 영향

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

본 연구는 비만 청소년 21명(남학생, 평균나이 13-14세)을 운동집단(11명)(12주, 40분, 주 5일)과 통제집단(10명)으로 무선 배정하였다. 심폐체력은 대사적 가스 분석기를 이용하여 최대산소섭취량을 측정하였으며, 신체조성은 전기저항법을 이용하여 측정하였다. 혈관 기능의 지표로써 경동맥-대퇴동맥 전파맥파 속도와 맥 증폭지수를 측정하였다. 본 연구에서, 허리둘레는 운동 집단에서 통제집단에서 보다 유의하게 감소되었다(ET 94.41±6.17 to 92.62±6.13 vs. CON 92.62±7.80 to 94.27±9.23 ㎝, p <.05). 심폐체력은 운동 집단에서 통제집단 보다 유의하게 증가되었다(ET 32.35±6.49 to 39.24±6.63 vs. CON 34.59±5.47 to 38.36±6.54 ㎖/㎏/min, p <.05). 체질량지수와 심혈관 위험 인자는 운동 집단에서 향상되지 않았다. 맥 증폭지수는 운동 집단에서 유의하게 증가하였으나(ET 1.60±0.45 to 1.87±0.58 vs. CON1.73±0.39 to 1.43±0.26%, p =<.05), 경동맥-대퇴동맥 맥파전파 속도는 유의하게 감소되지 않았다(ET 5.77±5.40 to 5.40±0.53 vs. CON 5.12±0.53 to 5.05±0.54 m/s, NS). 허리둘레 변화를 보정한 심폐체력의 변화는 맥증폭지수의 변화와 관련이 있었다(r=.457,p <.037). 이상의 결과를 종합해 보면 규칙적인 운동은 비만 청소년들의 혈관의 내피세포 기능을 향상시키며, 향상된 심폐체력은 체중의 감소와는 독립적으로 혈관 내피세포 기능과 관련이 있었다. 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.