scholarly journals Tetrahydrobiopterin improves endothelial function in patients with cystic fibrosis

2019 ◽  
Vol 126 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Jin Hee Jeong ◽  
Nichole Lee ◽  
Matthew A. Tucker ◽  
Paula Rodriguez-Miguelez ◽  
Jacob Looney ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cystic Fibrosis ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Function ◽  
Genetic Disorder ◽  
No Production ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
No Bioavailability

Cystic fibrosis (CF) is a genetic disorder associated with vascular endothelial dysfunction. Nitric oxide (NO) plays a major role in maintaining vascular function, and tetrahydrobiopterin (BH4) is a critical determinant of NO bioavailability. Thus the purpose of this study was to investigate the effects of oral administration of BH4 on endothelial function in patients with CF. Twenty-nine patients with CF (18 ± 8 yr old) and 29 healthy matched controls were recruited. Patients with CF participated in a randomized trial where they received a 5 mg/kg dose of oral BH4 (BH4-5; n = 17) or a 20 mg/kg dose of oral BH4 (BH4-20; n = 12). On a separate visit, a subset of patients from each group was retested following a placebo (PLC; n = 9). Brachial artery flow-mediated dilation (FMD) was used to evaluate vascular endothelial function, and a plasma sample was obtained before and 3 h after treatment. Cultured endothelial cells were treated with plasma to assess NO bioavailability. Baseline FMD was lower in patients compared with controls (5.7 ± 3.4 vs. 8.4 ± 3.5%, respectively, P = 0.005). No change in FMD was observed following PLC or BH4-5 (∆FMD: −0.8 ± 1.9% and −0.5 ± 2.5%; P = 0.273 and 0.132, respectively). Treatment with BH4-20, however, resulted in significant improvements in FMD (∆FMD: 1.1 ± 1.4%) compared with BH4-5 ( P = 0.023) and PLC ( P = 0.017). Moreover, BH4-20 significantly decreased endothelial cell superoxide production and increased NO production. These data suggest that a single oral dose of BH4 at 20 mg/kg improves vascular endothelial function in patients with CF, likely via increased endothelial NO synthase coupling. These findings support the hypothesis that loss of BH4 bioactivity contributes, in part, to endothelial dysfunction in patients with CF. NEW & NOTEWORTHY For the first time, the present study documents that a single dose of oral BH4 can improve vascular endothelial function in patients with cystic fibrosis (CF), and our in vitro data suggest this is via decreasing uncoupled nitric oxide. These data provide insight into the important role of BH4 bioactivity in vascular dysfunction and provide the foundation for further investigation into the chronic effects of BH4 treatment in patients with CF.

scholarly journals Sildenafil improves vascular endothelial function in patients with cystic fibrosis

2018 ◽  
Vol 315 (5) ◽  
pp. H1486-H1494 ◽  
Author(s):  
Paula Rodriguez-Miguelez ◽  
Nichole Lee ◽  
Matthew A. Tucker ◽  
Gábor Csányi ◽  
Kathleen T. McKie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cystic Fibrosis ◽  
Endothelial Function ◽  
Protein Expression ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Systemic Complications ◽  
Acute Dose ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Before And After

Cystic fibrosis (CF), characterized by defective CFTR function, is associated with multiple systemic complications, including vascular dysfunction. Sildenafil, a phosphodiesterase type 5 inhibitor, not only enhances nitric oxide (NO) metabolism but has been shown to improve CFTR functionality as well. Thus, sildenafil has been proposed as a therapy to improve vascular health in CF; however, its potential therapeutic role has yet to be determined. We sought to investigate the effect of sildenafil on endothelial function in patients with CF. Patients with CF completed a randomized, double-blind, placebo-controlled, crossover study with an acute dose of sildenafil (50 mg) or placebo followed by a 4-wk open-label extension with sildenafil (20 mg/day). Flow-mediated dilation (FMD) was used to evaluate endothelial function before and after treatments. In addition, phosphorylated endothelial NO synthase (pNOS3) and total NOS3 protein expression was determined from endothelial cells that were exposed to plasma from the patients before and after 4 wk of sildenafil treatment. No changes ( P ≥ 0.110) in endothelial function were observed after the acute dose of sildenafil. However, FMD significantly ( P = 0.029) increased after 4 wk of treatment (∆FMD: 1.5 ± 2.2%). Moreover, pNOS3 protein expression significantly ( P = 0.013) increased after 4 wk of treatment (∆pNOS3: 0.31 ± 0.39 arbitrary units) and was associated ( r = 0.593, P = 0.033) with the change in FMD. These data suggest that 4 wk of sildenafil treatment can improve vascular endothelial function in patients with CF, likely through an increase in NOS3 phosphorylation. NEW & NOTEWORTHY Findings from the present study demonstrate, for the first time, significant improvement of endothelial function in patients with cystic fibrosis treated with sildenafil that is associated with greater phosphorylation of endothelial nitric oxide synthase. These results support the use of sildenafil as a potential novel therapy for this patient population.

scholarly journals Endothelial Dysfunction in Cystic Fibrosis: Role of Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Matthew A. Tucker ◽  
Brandon M. Fox ◽  
Nichole Seigler ◽  
Paula Rodriguez-Miguelez ◽  
Jacob Looney ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Lipid Hydroperoxide ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Vascular Endothelial Function ◽  
Artery Flow

Oxidative stress and vascular endothelial dysfunction are established characteristics of cystic fibrosis (CF). Oxidative stress may contribute to vascular dysfunction via inhibition of nitric oxide (NO) bioavailability. Purpose. To determine if ingestion of a single antioxidant cocktail (AOC) improves vascular endothelial function in patients with CF. Methods. In 18 patients with CF (age 8-39 y), brachial artery flow-mediated dilation (FMD) was assessed using a Doppler ultrasound prior to and two hours following either an AOC (n=18; 1,000 mg vitamin C, 600 IU vitamin E, and 600 mg α-lipoic acid) or a placebo (n=9). In a subgroup of patients (n=9), changes in serum concentrations of α-tocopherol and lipid hydroperoxide (LOOH) were assessed following AOC and placebo. Results. A significant (p=0.032) increase in FMD was observed following AOC (Δ1.9±3.3%), compared to no change following placebo (Δ−0.8±1.9%). Moreover, compared with placebo, AOC prevented the decrease in α-tocopherol (Δ0.48±2.91 vs. −1.98±2.32 μM, p=0.024) and tended to decrease LOOH (Δ−0.2±0.1 vs. 0.1±0.1 μM, p=0.063). Conclusions. These data demonstrate that ingestion of an antioxidant cocktail can improve vascular endothelial function and improve oxidative stress in patients with CF, providing evidence that oxidative stress is a key contributor to vascular endothelial dysfunction in CF.

Abstract 174: Remote Ischemic Preconditioning Improves Digital Vascular Endothelial Function and Enhances Circulating Nitric Oxide Formation in Healthy Volunteers

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jun Tao ◽  
Xinzhu Tong
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Healthy Volunteers ◽  
Ischemic Preconditioning ◽  
Remote Ischemic Preconditioning ◽  
Control Group ◽  
No Production ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
No Formation

Background: Remote ischemic preconditioning (RIPC) induced by brief episodes of ischemia of the limb protects against organ damage by ischemia-reperfusion. It has been reported that RIPC improves endothelial function of the forearm in normal subjects and patients with coronary artery disease. However, the digital vascular endothelial response to RIPC has not been determined in healthy volunteers. Methods: This study was performed to examine effect of RIPC on fingertip digital vascular endothelial function by using endothelial pulse amplitude tonometry (EndoPAT) device and alteration in circulating nitric oxide(NO) level in peripheral blood. Ten healthy adult subjects (5 men, 5 women, mean age 25.2 years) had 3 cycles of 5 min ischemia alternating with 5 min reperfusion of the forearm. Another 10 healthy volunteers (6 men, 4 women, mean age 26.2 years) were used as the control group of sham and the cuff was inflated for 3 times at 10 mmHg for 5 minutes with 5-minute intervals. Fingertip digital vascular endothelial function of the ipsilateral arm was measured prior to first ischemia, 3h and 6h after the last episode of ischemia. Blood samples were taken from the contralateral arm prior to first ischemia, 3h and 6h after the last episode of ischemia. Results: Fingertip digital vascular endothelial function was significantly increase in 3h and 6h after the last RIPC intervention compared with the baseline condition(p<0.05). In parallel the RIPC stimulus increased circulating NO formation(p<0.05). There is a close association between finger vascular endothelial function and NO formation(p<0.05). Conclusion: The present findings demonstrate for the first time that transient RIPC contributes to improvement of digital vascular endothelial function and increase in circulating NO production in healthy volunteers. Our data provide a novel evidence to support that RIPC might gain even wider application not only in disease but also in health.

scholarly journals Effect of Strawberry Intake for 4 Weeks on Vascular Endothelial Function and Blood Pressure in Adults with Moderate Hypercholesterolemia (P06-128-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Di Xiao ◽  
Leailin Huang Huang ◽  
Indika Edirisinghe ◽  
Britt Burton-Freeman
Keyword(s):  
Blood Pressure ◽  
Endothelial Function ◽  
Vascular Function ◽  
Daily Intake ◽  
Random Order ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Freeze Dried ◽  
Pressure Independent ◽  
Hs Crp

Abstract Objectives The aim of this study is to investigate the effect of chronic strawberry intake on cardiovascular risk factors including fasting lipids concentrations, vascular endothelial function and blood pressure in middle-age overweight or obese individuals with moderate hypercholesterolemia. We hypothesized that 4-week strawberry intake would improve the lipids profile and concomitantly improve measures of vascular function. Methods In this randomized, double-blinded, controlled, crossover trial, thirty-four subjects (age 53 ± 1 years, BMI 31 ± 1 kg m-2, mean ± SD) consumed a strawberry beverage containing 25 gram freeze-dried strawberry powder or energy-matched control beverage in random order twice a day for 4 weeks. Treatment periods were separated by 4-week washout period. Fasting lipids, glucose, insulin, high sensitive c-reactive protein (hs-CRP), and postprandial flow-mediated dilation (FMD) and blood pressure, were measured at weeks 0, 4, 8 and 12. Results Fasting lipids, glucose, insulin, and hs-CRP did not differ between strawberry and control beverage interventions. In contrast, vascular function as measured by change in %FMD was significantly increased after strawberry compared to control after 4 weeks supplementation (4.3 ± 0.3% versus 3.6 ± 0.3%, respectively, p = 0.0096). In addition, %FMD was acutely increased from 0 to 1 hour after consuming strawberry beverage (p < 0.0001), which was consistent with reduced meal-induced increases in systolic blood pressure (SBP) postmeal (mean 2 hour changes in SBP after strawberry compared to control beverage, 2.3 ± 0.4 versus 3.4 ± 0.4 mmHg, p = 0.048). Conclusions Daily intake of strawberries may improve endothelial function and acute changes in blood pressure, independent of other metabolic changes, and may be considered a specific food/fruit to include in a heart-healthy diet in overweight or obese subjects with moderate hypercholesterolemia. Funding Sources California Strawberry Commission, Watsonville, CA, USA. Supporting Tables, Images and/or Graphs

scholarly journals Meta-analysis of Exercise Training on Vascular Endothelial Function in Cancer Survivors

2018 ◽  
Vol 17 (2) ◽  
pp. 192-199 ◽  
Author(s):  
Rhys I. Beaudry ◽  
Yuanyuan Liang ◽  
Steven T. Boyton ◽  
Wesley J. Tucker ◽  
R. Matthew Brothers ◽  
...  
Keyword(s):  
Exercise Training ◽  
Endothelial Function ◽  
Cancer Survivors ◽  
Vascular Function ◽  
Meta Analysis ◽  
Reactive Hyperemia ◽  
Controlled Trials ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Randomized Controlled

Cancer and cardiovascular disease (CVD) are leading causes of morbidity and mortality in the United States. Vascular endothelial dysfunction, an important contributor in the development of CVD, improves with exercise training in patients with CVD. However, the role of regular exercise to improve vascular function in cancer survivors remains equivocal. We performed a meta-analysis to determine the effect of exercise training on vascular endothelial function in cancer survivors. We searched PubMed (1975 to 2016), EMBASE CINAHL (1937 to 2016), OVID MEDLINE (1948 to 2016), and Cochrane Central Registry of Controlled Trials (1991 to 2016) using search terms: vascular function, endothelial function, flow-mediated dilation [FMD], reactive hyperemia, exercise, and cancer. Studies selected were randomized controlled trials of exercise training on vascular endothelial function in cancer survivors. We calculated pooled effect sizes and performed a meta-analysis. We identified 4 randomized controlled trials (breast cancer, n=2; prostate cancer, n=2) measuring vascular endothelial function by FMD (n=3) or reactive hyperemia index (n=1), including 163 cancer survivors (exercise training, n=82; control, n=81). Aerobic exercise training improved vascular function (n=4 studies; standardized mean difference [95% CI]=0.65 [0.33, 0.96], I2=0%; FMD, weighted mean difference [WMD]=1.28 [0.22, 2.34], I2=23.2%) and peak exercise oxygen uptake (3 trials; WMD [95% CI]=2.22 [0.83, 3.61] mL/kg/min; I2=0%). Our findings indicate that exercise training improves vascular endothelial function and exercise capacity in breast and prostate cancer survivors.

scholarly journals SUMO2 regulates vascular endothelial function and oxidative stress in mice

2019 ◽  
Vol 317 (6) ◽  
pp. H1292-H1300 ◽  
Author(s):  
Young-Rae Kim ◽  
Julia S. Jacobs ◽  
Qiuxia Li ◽  
Ravinder Reddy Gaddam ◽  
Ajit Vikram ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Function ◽  
Vascular Function ◽  
Ex Vivo ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Density Lipoprotein Receptor ◽  
Vascular Oxidative Stress

SUMOylation is a posttranslational modification of lysine residues. Modification of proteins by small ubiquitin-like modifiers (SUMO)1, -2, and -3 can achieve varied, and often unique, physiological and pathological effects. We looked for SUMO2-specific effects on vascular endothelial function. SUMO2 expression was upregulated in the aortic endothelium of hypercholesterolemic low-density lipoprotein receptor-deficient mice and was responsible for impairment of endothelium-dependent vasorelaxation in these mice. Moreover, overexpression of SUMO2 in aortas ex vivo, in cultured endothelial cells, and transgenically in the endothelium of mice increased vascular oxidative stress and impaired endothelium-dependent vasorelaxation. Conversely, inhibition of SUMO2 impaired physiological endothelium-dependent vasorelaxation in normocholesterolemic mice. These findings indicate that while endogenous SUMO2 is important in maintenance of normal endothelium-dependent vascular function, its upregulation impairs vascular homeostasis and contributes to hypercholesterolemia-induced endothelial dysfunction. NEW & NOTEWORTHY Sumoylation is known to impair vascular function; however, the role of specific SUMOs in the regulation of vascular function is not known. Using multiple complementary approaches, we show that hyper-SUMO2ylation impairs vascular endothelial function and increases vascular oxidative stress, whereas endogenous SUMO2 is essential for maintenance of normal physiological function of the vascular endothelium.

The effect of nitric oxide synthase 4ab gene polymorphism on vascular endothelial function in healthy subjects

2003 ◽  
Vol 12 (2) ◽  
pp. A55
Author(s):  
Bill Bilsborough ◽  
Daniel J. Green ◽  
Cyril D.S. Mamotte ◽  
Frank M. van Bockxmeer ◽  
Gerry O'Driscoll ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Gene Polymorphism ◽  
Endothelial Function ◽  
Healthy Subjects ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Oxide Synthase

scholarly journals Abstract 236: Aldehydes in Cigarette Smoke Impair Vascular Endothelial Function

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Poonam Rao ◽  
Pooneh Nabavizadeh Rafsanjani ◽  
Daniel Han ◽  
Suzaynn Schick ◽  
Matthew Springer
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Cigarette Smoke ◽  
Secondhand Smoke ◽  
Negative Control ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Gas Generation ◽  
Post Exposure

Introduction: Exposure to tobacco and marijuana smoke impairs vascular endothelial function. While the particulate phase of smoke is heavily implicated, the role of volatile constituents is unclear. Smoke contains aldehydes, which are known to cause endothelial dysfunction. We explored whether two aldehydes found in smoke, acrolein and acetaldehyde, can induce endothelial dysfunction. Hypothesis: Aldehydes in smoke impair endothelial function. Methods: We exposed 4 groups of anesthetized rats to 3 ppm acrolein and 10-11.5 ppm acetaldehyde gases (concentrations relevant to levels in secondhand smoke), Marlboro Red cigarette sidestream smoke at modest levels (600 μg/m 3 PM2.5) as a positive control, and clean air through the gas generation system as a negative control. Exposure was continuous for 10 minutes. Endothelial function (flow-mediated dilation; FMD) was quantified pre- and post-exposure by measuring femoral artery diameter with ultrasound before and after 5 min of transient ischemia and expressed as % vasodilation. Results: Impairment of FMD was observed for acrolein (10.8±1.7(SD)% vs. 5.8±2.9%, p=.001), acetaldehyde (8.8±2.0% vs. 6.0±2.5%, p=.001), and cigarette smoke (9.4±2.9% vs. 5.8±2.0%, p=.002), but not for air (7.9±2.0% vs. 9±3.2%, p=.44) (figure; each colored line denotes a rat pre- and post-exposure; bars denote means). Conclusions: Acrolein and acetaldehyde at levels found in secondhand smoke impair endothelial function. Our results suggest that despite a potential role of particles, volatile aldehydes may mediate part of the endothelial dysfunction caused by exposure to smoke.

Sign in / Sign up

Export Citation Format

Share Document