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Pharmacokinetic Parameters of Watermelon (Rind, Flesh, and Seeds) Bioactive Components in Human Plasma: A Pilot Study to Investigate the Relationship to Endothelial Function.
Fan, J, Park, E, Zhang, L, Edirisinghe, I, Burton-Freeman, B, Sandhu, AK
Journal of agricultural and food chemistry. 2020;(28):7393-7403
Abstract
This study aimed to investigate the metabolic fate of bioactive components in watermelon and explore their effect on endothelial function. Six healthy overweight/obese (BMI: 28.7 ± 1.6 kg/m2) adults received 100 kcal of watermelon flesh (WF), rind (WR), seeds (WS), or control meal. l-Citrulline, arginine, and (poly)phenolic metabolites were characterized in plasma over 24 h using UHPLC-MS. Endothelial function was assessed using a flow mediated dilation (FMD) technique over 7 h. Maximum concentration (Cmax) and area under the curve (AUC0-8h) of l-citrulline were significantly higher after WF- and WR-containing test meals compared to control (p < 0.05). Likewise, several individual phenolic metabolites in plasma had significantly higher Cmax after WR, WF, or WS intake compared to control. FMD responses were not different among test meals. Our results provide insights on circulating metabolites from watermelon flesh, seed, and rind and lay the foundation for future clinical trials on vascular benefits of watermelon.
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The effect of vitamin E supplementation on biomarkers of endothelial function and inflammation among hemodialysis patients: A double-blinded randomized clinical trial.
Pirhadi-Tavandashti, N, Imani, H, Ebrahimpour-Koujan, S, Samavat, S, Hakemi, MS
Complementary therapies in medicine. 2020;:102357
Abstract
OBJECTIVES The present study was aimed to investigate the effect of alpha-tocopherol supplementation on biomarkers of endothelial function (Intercellular Adhesion Molecule 1 and Vascular Cell Adhesion Protein 1) and inflammatory markers (Interleukin 6 and high-sensitivity C-reactive protein) among the hemodialysis patients. METHODS To conduct this randomized, double-blinded, and placebo-controlled clinical trial, 49 hemodialysis patients, aged 20-60 years, were recruited and randomly divided into the intervention and control groups. The intervention group (n = 25) received 600 IU alpha-tocopherol soft gels (200 IU three times daily), while the controls (n = 24) consumed the identical placebo soft gels for 10 weeks. At the baseline and end of the study, 7 ml pre-dialysis blood samples were taken from all participants to measure their serum concentrations of ICAM-1, VCAM-1, IL-6, and hs-CRP. RESULTS Alpha-tocopherol supplementation reduced the serum levels of ICAM-1 and VCAM-1 significantly (-140.67 ± 57.25 ng/ml vs. -15.97 ± 79.19 ng/ml, P = 0.001 for ICAM-1 and --6.79 ± 4.76 ng/ml vs. 1.02 ± 3.22 ng/ml, P = 0.019 for VCAM-1). However, no significant difference was observed between the two groups regarding the serum levels of hs-CRP (-0.15 ± 0.19 mg/l vs. 0.02 ± 0.12 mg/l; P = 0.32) and IL-6 (-0.03 ± 0.1 pg/ml vs. - 0.06 ± 0.11 pg/ml; P = 0.65). CONCLUSIONS Our results showed that 10 weeks of supplementation with 600 IU alpha-tocopherol improved ICAM-1 and VCAM-1 levels, but did not have any effect on the serum concentration of IL-6 and hs-CRP in hemodialysis patients. Further studies are required to confirm these findings.
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Effects of pomegranate peel extract and vitamin E on the inflammatory status and endothelial function in hemodialysis patients: a randomized controlled clinical trial.
Jafari, T, Fallah, AA, Reyhanian, A, Sarmast, E
Food & function. 2020;(9):7987-7993
Abstract
Inflammation and endothelial dysfunction are major problems in hemodialysis (HD) patients. This study assessed the effects of an 8 week administration of pomegranate peel extract (PPE) and vitamin E (Vit E) alone or in combination on the biomarkers of inflammation, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and the biomarkers of endothelial function, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin, in HD patients. In a randomized, double-blind, parallel, placebo-controlled trial, 100 HD patients were randomly divided into 4 equal groups: (a) PPE + Vit E, received 2 pomegranate tablets (each tablet contained 225 mg PPE, equal to 90 mg ellagic acid) + 1 Vit E soft gel (400 IU) daily, (b) PPE, received 2 pomegranate tablets + 1 Vit E placebo soft gel daily, (c) Vit E, received 1 Vit E soft gel + 2 pomegranate placebo tablets daily, and (d) placebo, received 2 pomegranate placebo tablets + 1 Vit E placebo soft gel daily. For group allocation, a stratified block randomization procedure based on sex, age, and HD duration was used. Each intervention product and its placebo had identical shape, color, size, and packaging. Consumption of PPE + Vit E significantly reduced the serum CRP level (mean change: -7.12 ± 4.59 mg l-1, P < 0.001) compared to other groups, while reduced levels of IL-6 (mean change: -2.19 ± 2.33 pg ml-1, P < 0.001), TNF-α (mean change: -2.41 ± 3.21 pg ml-1, P = 0.008), ICAM-1 (mean change: -64.2 ± 111.0 ng ml-1, P = 0.017), and VCAM-1 (mean change: -117.7 ± 177.1 ng ml-1, P = 0.002) were observed compared to the control. There was no significant difference in the P-selectin level among the groups. Consumption of PPE or Vit E alone significantly reduced the CRP level (mean change for PPE: -3.58 ± 5.41 mg l-1, P < 0.001; mean change for Vit E: -3.25 ± 8.29 mg l-1, P = 0.002) compared to the control. As a result, consumption of PPE in combination with Vit E enhanced the inflammatory status and endothelial function in HD patients.
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Sitting decreases endothelial microparticles but not circulating angiogenic cells irrespective of lower leg exercises: a randomized cross-over trial.
Evans, WS, Hanson, ED, Shill, DD, Landers-Ramos, RQ, Stoner, L, Willey, Q, Credeur, DP, Prior, SJ
Experimental physiology. 2020;(8):1408-1419
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Abstract
NEW FINDINGS What is the central question of this study? What are the cellular and molecular determinants of increased risk for cardiovascular disease from prolonged sitting? What is the main finding and its importance? Prolonged sitting, independent of calf raise interruption strategies, decreases microparticle counts linked to endothelial activation and apoptosis. An acute bout of prolonged sitting appears to promote paradoxical decreases in microparticle counts, but the implications are not yet clear. ABSTRACT Repeated exposure to prolonged sitting increases the risk for cardiovascular disease. However, the cellular links by which repeated exposure to prolonged sitting lead to increased cardiovascular risk have not been fully elucidated, with markers of vascular damage and repair such as microparticles (MPs) and circulating angiogenic cell (CACs) being promising targets. The objective of the study was to examine the effects of 3 h of sitting with or without intermittent calf raises on annexin V+ /CD34+ , annexin V+ /CD62E+ , and annexin V+ /CD31+ /42b- MP populations linked to CAC paracrine activity, endothelial activation and apoptosis, respectively, as well as CD14+ /31+ , CD3+ /31+ , and CD34+ CACs, which are linked to endothelial repair. In a random order, 20 sedentary participants (14 females, 22 ± 3 years) remained seated for 180 min with or without performing 10 calf raises every 10 min. Blood samples were obtained after 20 min of quiet rest in the supine position before and after sitting. Overall, sitting decreased annexin V+ /CD34+ MPs (-12 ± 5 events µl-1 , P < 0.01), annexin V+ /CD62E+ MPs (-17 ± 4 events µl-1 , P < 0.001), and annexin V+ /CD31+ /42b- MPs (-22 ± 6 events µl-1 , P < 0.001) regardless of condition. There were no differences in endothelin-1 plasma concentration, CD14+ /31+ , CD34+ or CD3+ /31+ CAC frequencies. Sitting did not alter CAC number, but decreased MPs linked to endothelial activation, apoptosis and CAC paracrine activity in a manner that was independent of muscle contraction. These findings support changes in markers of endothelial activation and apoptosis with sedentary behaviour and provide new insights into altered intercellular communication with physical inactivity such as prolonged sitting.
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Evaluation of the Effect Derived from Silybin with Vitamin D and Vitamin E Administration on Clinical, Metabolic, Endothelial Dysfunction, Oxidative Stress Parameters, and Serological Worsening Markers in Nonalcoholic Fatty Liver Disease Patients.
Federico, A, Dallio, M, Masarone, M, Gravina, AG, Di Sarno, R, Tuccillo, C, Cossiga, V, Lama, S, Stiuso, P, Morisco, F, et al
Oxidative medicine and cellular longevity. 2019;:8742075
Abstract
Nowadays, the nonalcoholic fatty liver disease represents the main chronic liver disease in the Western countries, and the correct medical therapy remains a big question for the scientific community. The aim of our study was to evaluate the effect derived from the administration for six months of silybin with vitamin D and vitamin E (RealSIL 100D®) on metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease markers in nonalcoholic fatty liver disease patients. We enrolled 90 consecutive patients with histological diagnosis of nonalcoholic fatty liver disease and 60 patients with diagnosis of reflux disease (not in therapy) as healthy controls. The nonalcoholic fatty liver disease patients were randomized into two groups: treated (60 patients) and not treated (30 patients). We performed a nutritional assessment and evaluated clinical parameters, routine home tests, the homeostatic model assessment of insulin resistance, NAFLD fibrosis score and fibrosis-4, transient elastography and controlled attenuation parameter, thiobarbituric acid reactive substances, tumor necrosis factor α, transforming growth factor β, interleukin-18 and interleukin-22, matrix metalloproteinase 2, epidermal growth factor receptor, insulin growth factor-II, cluster of differentiation-44, high mobility group box-1, and Endocan. Compared to the healthy controls, the nonalcoholic fatty liver disease patients had statistically significant differences for almost all parameters evaluated at baseline (p < 0.05). Six months after the baseline, the proportion of nonalcoholic fatty liver disease patients treated that underwent a statistically significant improvement in metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease was greater than not treated nonalcoholic fatty liver disease patients (p < 0.05). Even more relevant results were obtained for the same parameters by analyzing patients with a concomitant diagnosis of metabolic syndrome (p < 0.001). The benefit that derives from the use of RealSIL 100D could derive from the action on more systems able to advance the pathology above all in that subset of patients suffering from concomitant metabolic syndrome.
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Rationale and design of a multicenter placebo-controlled double-blind randomized trial to evaluate the effect of empagliflozin on endothelial function: the EMBLEM trial.
Tanaka, A, Shimabukuro, M, Okada, Y, Taguchi, I, Yamaoka-Tojo, M, Tomiyama, H, Teragawa, H, Sugiyama, S, Yoshida, H, Sato, Y, et al
Cardiovascular diabetology. 2017;(1):48
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is characterized by systemic metabolic abnormalities and the development of micro- and macrovascular complications, resulting in a shortened life expectancy. A recent cardiovascular (CV) safety trial, the EMPA-REG OUTCOME trial, showed that empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, markedly reduced CV death and all-cause mortality and hospitalization for heart failure in patients with T2DM and established CV disease (CVD). SGLT2 inhibitors are known to not only decrease plasma glucose levels, but also favorably modulate a wide range of metabolic and hemodynamic disorders related to CV pathways. Although some experimental studies revealed a beneficial effect of SGLT2 inhibitors on atherosclerosis, there is a paucity of clinical data showing that they can slow the progression of atherosclerosis in patients with T2DM. Therefore, the EMBLEM trial was designed to investigate whether empagliflozin treatment can improve endothelial function, which plays a pivotal role in the pathogenesis of atherosclerosis, in patients with T2DM and established CVD. METHODS The EMBLEM trial is an ongoing, prospective, multicenter, placebo-controlled double-blind randomized, investigator-initiated clinical trial in Japan. A total of 110 participants with T2DM (HbA1c range 6.0-10.0%) and with established CVD will be randomized (1:1) to receive either empagliflozin 10 mg once daily or a placebo. The primary endpoint of the trial is change in the reactive hyperemia (RH)-peripheral arterial tonometry-derived RH index at 24 weeks from baseline. For comparison of treatment effects between the treatment groups, the baseline-adjusted means and their 95% confidence intervals will be estimated by analysis of covariance adjusted for the following allocation factors: HbA1c (<7.0 or ≥7.0%), age (<65 or ≥65 years), systolic blood pressure (<140 or ≥140 mmHg), and current smoking status (nonsmoker or smoker). Key secondary endpoints include the change from baseline for other vascular-related markers such as arterial stiffness, sympathetic nervous activity, and parameters of cardiac and renal function. Importantly, serious adverse effects independently on the causal relationship to the trial drugs and protocol will be also evaluated throughout the trial period. DISCUSSION EMBLEM is the first trial to assess the effect of empagliflozin on endothelial function in patients with T2DM and established CVD. Additionally, mechanisms associating empagliflozin-mediated actions with endothelial function and other CV markers will be evaluated. Thus, the trial is designed to elucidate potential mechanisms by which empagliflozin protects CV systems and improves CV outcomes. Trial registration Unique Trial Number, UMIN000024502 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028197 ).
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One-year daily consumption of buttermilk drink containing lutein-enriched egg-yolks does not affect endothelial function in fasting and postprandial state.
van der Made, SM, Berendschot, TTJM, Kijlstra, A, Plat, J
Scientific reports. 2017;(1):1353
Abstract
Previous results have shown that one-year daily consumption of a lutein-enriched egg yolk containing dairy drink did not significantly affect fasting serum lipid and lipoprotein concentrations in adults with early signs of macular degeneration. The current study further substantiates these findings with parameters reflecting endothelial function. Additionally, we extend our observations from the fasting to the postprandial situation. Subjects participated in a 1-y randomized placebo-controlled dietary intervention trial. 52 subjects were included in the active (Egg) group and 49 in the control (Con) group. Changes in postprandial biochemistry (triacylglycerol (TAG), glucose and non-esterified fatty acids (NEFA)) following a mixed meal and flow-mediated dilation (FMD) analyses were evaluated at the start and after one year intervention. Postprandial glycemic and lipemic responses before the intervention as well as the differences in postprandial responses after one-year intervention were comparable between the Egg and the Con group. Fasting FMD was comparable between the groups before the intervention started and at the end of intervention. Additionally, the change in FMD following a mixed meal was comparable between the groups. To conclude, one-year consumption of a lutein-enriched egg yolk incorporated in a dairy drink has no effect on postprandial lipid and glucose metabolism or endothelial function.
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Repeated supra-maximal sprint cycling with and without sodium bicarbonate supplementation induces endothelial microparticle release.
Kirk, RJ, Peart, DJ, Madden, LA, Vince, RV
European journal of sport science. 2014;(4):345-52
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Abstract
Under normal homeostatic conditions, the endothelium releases microparticles (MPs), which are known to increase under stressful conditions and in disease states. CD105 (endoglin) and CD106 (vascular cell adhesion molecule-1) are expressed on the surface of endothelial cells and increased expression in response to stress may be observed. A randomised-controlled double-blinded study aimed to examine the use of endothelial MPs as a marker for the state of one's endothelium, as well as whether maintaining acid-base homeostasis affects the release of these MPs. This study tested seven healthy male volunteers, who completed a strenuous cycling protocol, with venous blood analysed for CD105+ and CD106+ MPs by flow cytometry at regular intervals. Prior to each trial participants consumed either 0.3 g·kg(-1) body mass of sodium bicarbonate (NaHCO3), or 0.045 g·kg(-1) body mass of sodium chloride (NaCl). A significant rise in endothelial CD105+ MPs and CD106+ MPs (p<0.05) was observed at 90 min post-exercise. A significant trend was shown for these MPs to return to resting levels 180 min post-exercise in both groups. No significance was found between experimental groups, suggesting that maintaining acid-base variables closer to basal levels has little effect upon the endothelial stress response for this particular exercise mode. In conclusion, strenuous exercise is accompanied by MP release and the endothelium is able to rapidly recover in healthy individuals, whilst maintaining acid-base homeostasis does not attenuate the MP release from the endothelium after exercise.
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Orlistat improves endothelial function in obese adolescents: a randomised trial.
Yu, CC, Li, AM, Chan, KO, Chook, P, Kam, JT, Au, CT, So, RC, Sung, RY, McManus, AM
Journal of paediatrics and child health. 2013;(11):969-975
Abstract
AIM: To investigate the effect of orlistat on endothelial function in obese adolescents. METHODS Single-blind 10-week controlled trial of 67 normolipidaemic obese adolescents randomised into three groups. Group 1 (diet alone), Group 2 (diet and orlistat), Group 3 (diet, orlistat and exercise). Endothelial function measured by flow-mediated dilatation (FMD) of the brachial artery, anthropometric parameters, blood pressure, fasting blood lipids, insulin and glucose levels were recorded at baseline and at 10 weeks. RESULTS Sixty four subjects completed the study. Groups were comparable at baseline. FMD increased significantly with orlistat (Groups 2 and 3) but not in Group 1. Orlistat treatment resulted in significantly reduced bodyweight, body mass index (BMI), waist circumference, total and low-density lipoprotein (LDL) cholesterol levels. High-density lipoprotein cholesterol levels were unchanged. Triglyceride and insulin levels were significantly reduced in all three groups. The reduction in cholesterols did not correlate with reductions in weight and BMI. A slight reduction of body fat, both with and without orlistat treatment, correlated with reduction in BMI after adjustment for baseline values. Blood pressure was unaltered by orlistat. Calorie intake was reduced with orlistat, and the decrease noted in % fat and increase in % carbohydrate was significant only in those taking orlistat. The addition of exercise (Group 3 compared with Group 2) altered no parameter. CONCLUSIONS Orlistat improves endothelial function and reduces bodyweight, BMI, fasting total and LDL-cholesterol in obese adolescents when combined with dietary control. Improvement in endothelial function if maintained could reflect long-term cardiovascular benefit.
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Comparison of sevelamer and calcium carbonate on endothelial function and inflammation in patients on peritoneal dialysis.
Chennasamudram, SP, Noor, T, Vasylyeva, TL
Journal of renal care. 2013;(2):82-9
Abstract
BACKGROUND Hyperphosphataemia is a known independent risk factor for cardiovascular mortality. The objective of the study was to compare the effects of two phosphate binders, sevelamer carbonate and calcium carbonate on endothelial function (EF) and inflammation in patients on peritoneal dialysis (PD) with Type 2 diabetes mellitus (T2DM). METHODS Fifteen subjects with hyperphosphataemia discontinued all phosphate binders to undergo a two-week washout and were assigned to sevelamer carbonate or calcium carbonate treatments for eight weeks. After a second two-week washout period, subjects crossed over to either of the alternate treatments for another eight weeks. At the beginning and end of each treatment, biomarkers of EF, pro-inflammatory cytokines, serum albumin, calcium, phosphate and lipids were measured. RESULTS Sevelamer carbonate significantly improved lipid profile compared with calcium carbonate. Amongst the EF and pro-inflammatory biomarkers, sevelamer carbonate decreased serum endothelin-1, plasminogen activator inhibitor-1, C-reactive protein and interleukin-6. Both phosphate binders were effective in decreasing serum phosphate but sevelamer had a positive effect on EF. CONCLUSIONS Treatment with sevelamer carbonate has beneficial effects compared with calcium carbonate in decreasing inflammation and improving EF in patients with T2DM on PD.