Search

Abstract The purpose of this study was to determine the effect of circulating microvesicles isolated from chronic electronic (e‐)cigarette users on cultured human umbilical vein endothelial cell (HUVEC) expression of nuclear factor‐κB (NF‐κB), cellular cytokine release, phosphorylation of endothelial nitric oxide synthase (eNOS) and NO production. The HUVECs were treated with microvesicles isolated via flow cytometry from nine non‐tobacco users (five male and four female; 22 ± 2 years of age) and 10 e‐cigarette users (six male and four female; 22 ± 2 years of age). Microvesicles from e‐cigarette users induced significantly greater release of interleukin‐6 (183.4 ± 23.6 vs. 150.6 ± 15.4 pg/mL; P = 0.002) and interleukin‐8 (160.0 ± 31.6 vs. 129.4 ± 11.2 pg/mL; P = 0.01), in addition to expression of p‐NF‐κB p65 (Ser536) (18.8 ± 3.4 vs. 15.6 ± 1.5 a.u.; P = 0.02) from HUVECs compared with microvesicles from non‐tobacco users. Nuclear factor‐κB p65 was not significantly different between microvesicles from the non‐tobacco users and from the e‐cigarette users (87.6 ± 8.7 vs. 90.4 ± 24.6 a.u.; P = 0.701). Neither total eNOS (71.4 ± 21.8 vs. 80.4 ± 24.5 a.u.; P = 0.413) nor p‐eNOS (Thr495) (229.2 ± 26.5 vs. 222.1 ± 22.7 a.u.; P = 0.542) was significantly different between microvesicle‐treated HUVECs from non‐tobacco users and e‐cigarette users. However, p‐eNOS (Ser1177) (28.9 ± 6.2 vs. 45.8 ± 9.0 a.u.; P

Background Microparticles and endothelial microparticles (EMPs) are implicated in accelerating cardiovascular disease (CVD); however, data in pediatrics are limited. We examined the relationship of microparticles and EMPs with adiposity and subclinical CVD risk measures in a pediatric population to determine their potential as biomarkers of CVD risk. Methods and Results A cross‐sectional study of youth (n=280; ages 8–20 years) with a range of body mass index categories was used. Microparticles, EMPs, and activated EMPs were measured by flow cytometry. %Body fat and %visceral adipose tissue were measured by dual X‐ray absorptiometry. Measures of arterial stiffness and vascular wall structure were obtained. Linear regression (with log‐transformed outcomes) and logistic regression were used to evaluate associations and all results were exponentiated. Youth with overweight/obesity and severe obesity had 2.50 (95% CI, 1.56–4.01) and 3.42 (95% CI, 2.15–5.43) times the geometric means of the total number of microparticles, respectively, compared with those with normal weight. Youth with overweight/obesity and severe obesity had 1.97 (95% CI, 1.09–3.55) and 2.34 (95% CI, 1.31–4.19) times the geometric means of the total number of EMPs, respectively, compared with those with normal weight. There were positive associations between the levels of both microparticles and EMPs with higher adiposity measures and poor CVD risk measures. Youth with higher adiposity showed 1.84 times the odds of having high levels of activated EMPs (%) (odds ratio, 1.84; 95% CI, 1.08–3.14) compared with those with normal weight. Conclusions Levels of microparticles, EMPs, and activated EMPs were positively associated with adiposity and poor subclinical CVD risk in a pediatric population.

Abstract Background Cardiovascular disease frequently causes morbidity and mortality in mucopolysaccharidoses (MPS); however, cardiovascular anatomy and dysfunction in MPS IVA (Morquio A disease) is not well described. Consequently, the study aimed to compare carotid artery structure and elasticity of MPS IVA patients with other MPS patients and healthy control subjects, and quantitate frequency of MPS IVA cardiac structural and functional abnormalities. Methods Prospective, multi-center echocardiogram and carotid ultrasound evaluations of 12 Morquio A patients were compared with other MPS and healthy control subjects. Average differences between groups were adjusted for age, sex, and height with robust variance estimation for confidence intervals and P-values. Results Morquio A patients demonstrated significantly higher (P

Background Circulating endothelial cells (CECs) reflect early changes in endothelial health; however, the degree to which CEC number and activation is related to adiposity and cardiovascular risk factors in youth is not well described. Methods and Results Youth in this study (N=271; aged 8–20 years) were classified into normal weight (body mass index [BMI] percentage 0.05). Youth with severe obesity had a higher degree of CEC activation compared with normal weight youth (8.3%; 95% CI, 1.1–15.6 [P=0.024]). Higher CEC number was associated with greater body fat percentage (0.02 per percentage; 95% CI, 0.00–0.03 [P=0.020]) and systolic blood pressure percentile (0.01 per percentage; 95% CI, 0.00–0.01 [P=0.035]). Higher degree of CEC activation was associated with greater visceral adipose tissue (5.7% per kg; 95% CI, 0.4–10.9 [P=0.034]) and non–high‐density lipoprotein cholesterol (0.11% per mg/dL; 95% CI, 0.01–0.21 [P=0.039]). Conclusions Methods of CEC quantification are associated with adiposity and cardiometabolic risk factors and may potentially reflect accelerated atherosclerosis as early as childhood.

Ventilation/carbon dioxide production (VE/VCO2slope) is used clinically to determine cardiorespiratory fitness and morbidity in heart failure (HF). Previously, we demonstrated that lower lean leg mass is associated with high VE/VCO2slope during exercise in HF. In healthy individuals, we evaluated 1) whether VE/VCO2slope differed between lean and overweight women and 2) the relationship between lean leg mass and VE/VCO2slope in overweight sedentary (OWS), overweight trained (OWTR) and lean, trained (LTR) women. Methods: Gas exchange and ventilation were collected during a treadmill peak oxygen uptake test (VO2peak) in 40 women [26 OWS (29 ± 7 yrs., mean ± SD), 7 OWTR (33 ± 5 yrs) and 7 LTR (26 ± 6 yrs)]. Body composition was measured by dual X-ray absorptiometry. Results: VO2peak was highest in LTR (46.6 ± 8 ml/kg/min) compared with OWTR (38.1 ± 4.9 ml/kg/min) and OWS women (25.3 ± 4.8 ml/kg/min, p 0.05). Higher lean leg mass was associated with lower VE/VCO2slope in overweight women (OWS + OWTR: r = −0.55, p

Purpose: To investigate cerebral blood flow (CBF) characteristics before and after hemodialysis initiation and their longitudinal associations with global cognitive function in older adults. Methods: A cohort of 17 older end-stage renal disease patients anticipating standard thrice-weekly hemodialysis and a group of 11 age- and sex-matched healthy control volunteers were recruited for brain perfusion imaging studies using arterial spin labeling. Hemodialysis patients participated in a prospective longitudinal study using brain magnetic resonance imaging and global cognitive assessment using the Modified Mini-Mental State Examination (3MS) at two time points: baseline, 2.9 ± 0.9 months before, and follow-up, 6.4 ± 2.4 months after hemodialysis initiation. Healthy controls were imaged once using the same protocol. CBF analyses were performed globally in grey and white matter and regionally in the hippocampus and orbitofrontal cortex. Covariate-adjusted linear mixed-effects models were used for statistical analyses (significance: p

Objectives: Although physical activity ameliorates the metabolic impact of high body mass index (BMI), runners with BMI ≥25 kg/m2 are relatively understudied. This study had two goals: (1) to identify differences in body composition, as measured by dual X-ray absorptiometry (DXA), between overweight (BMI ≥ 25 kg/m2) runners (OWR) and normal weight (BMI

BackgroundUnderstanding the heritable contribution of vascular measures, from parent to offspring, may aid in risk stratification and atherosclerosis prevention efforts. We hypothesized that measures of vascular structure and function would be heritable in this cohort of parents and their adolescent offspring. Methods and ResultsHigh‐resolution ultrasound scans of the brachial and carotid arteries were obtained in parents (n=558) and their offspring (n=369). Lumen diameter and flow‐mediated dilation were measured in the brachial artery. Intima‐media thickness, lumen diameter, incremental elastic modulus, diameter distensibility, and cross‐sectional distensibility were measured, and carotid cross‐sectional compliance was measured in the carotid artery. Carotid–radial pulse wave velocity was obtained using SphygmoCor®. Heritability analysis (h2, expressed as %) using Sequential Oligogenic Linkage Analysis Routines was performed on the entire cohort and adjusted for age, sex, race, body–mass index, smoking, and mean arterial pressure. Data are presented as mean±SE. Measures of brachial artery diameter (h2=25±9%, P=0.001), lumen diameter (h2=55±9%, P

The aim of the present study was to investigate the impact of acute hyperglycaemia on endothelial function in both normal-weight and overweight children. A total of 16 overweight [BMI (body mass index) ≥85th percentile] and 15 normal-weight (BMI <85th percentile) children were evaluated for FMD (flow-mediated dilation) at baseline and 30, 60 and 120 min after glucose ingestion. At 15 min following the measurement of the final FMD, 0.3 mg of sublingual nitroglycerine was administered and the brachial artery was imaged in order to assess endothelium-independent dilation. By design, the overweight children were significantly heavier (63.2±4.6 compared with 41.3±2.5 kg; P=0.0003) and had a greater percentage body fat (43.9±1.8 compared with 23.8±2.05%; P<0.0001) than the normal-weight children. The area under the curve in response to glucose administration was significantly (P<0.0001) greater in the overweight group for both glucose and insulin. The FMD area under the curve was not significantly different at baseline or between time points after glucose ingestion, nor was there a difference in response between the two groups. Endothelium-independent dilation in the normal-weight group was significantly greater compared with the overweight group (26.7±1.6 compared with 20.2±2.0% respectively; P=0.019). In conclusion, these results suggest that acute elevation of glucose and insulin in overweight and normal-weight children are not associated with impairment in endothelial function. [ABSTRACT FROM AUTHOR]

Objective: To examine the association of age, sex, and obesity status on endothelial-independent dilation (EID) among children and adolescents. Study design: This study examined 264 children (143 males) between 8 to 18 years old (mean  ±  SD: age  =  14.3  ±  2.7 years). Endothelial-independent dilation was assessed via ultrasound imaging of the brachial artery following administration of 0.3 milligrams of sublingual nitroglycerin. A one-way analysis of variance with Bonferroni post hoc comparisons assessed sex-differences in percent peak EID dilation (EID%-peak) and EID area under the curve (EID%-AUC), while analysis of covariance (ANCOVA) adjusted for race, age, body mass index percentile (BMI-percentile), and brachial artery diameter. Multiple linear regression evaluated the association of sex, age, BMI-percentile, percent body fat (%BF), and brachial artery diameter on EID. Results: Prior to adjustment, EID%-peak was significantly higher among females than males (mean  ±  SE: 26.9  ±  0.5% versus 22.9  ±  0.6%, p  <  0.001, respectively); similar findings for EID%-AUC (4214%  ±  105%·s versus 3398%  ±  97%·s, p  <  0.001) were observed. After adjusting for covariates, EID%-AUC remained consistent (p  =  0.03) while EID%-peak was not significantly different between sexes (p  =  0.21). EID%-peak was significantly higher among normal weight compared to obese participants (p  =  0.04), while no differences were observed between obesity status after adjustment for brachial artery diameter (p  =  0.64). Both unadjusted (p  =  0.16) and adjusted EID%-AUC (p  =  0.24) was not significantly different between obesity status. BMI-percentile was not associated with EID%-peak (p  =  0.76) or EID%-AUC (p  =  0.30). Additionally, %BF was not associated with EID%-peak (p  =  0.56) or EID%-AUC (p  =  0.15). After adjusting for brachial artery diameter, BMI-percentile, and age, males had lower EID%-AUC (p  =  0.03) and lower but not significant EID%-peak (p  =  0.21). Significance: Vascular smooth muscle function was significantly lower among male children and adolescents, which is suggestive that impaired EID and increased cardiovascular disease risk among males may begin in childhood. Interestingly, obesity status and BMI-percentile was not associated with EID in children and adolescents after adjusting for brachial artery diameter. [ABSTRACT FROM AUTHOR]

Flow-mediated dilation (FMD) relies on reactive hyperemia to stimulate the endothelium to release nitric oxide, causing smooth muscle relaxation. Hypercapnia also produces vasodilation, which is thought to be nitric oxide-independent. The purpose of this study was to compare and contrast the effects of hypercapnia and reactive hyperemia as stimuli for brachial artery dilation. On separate days, twenty-five participants underwent vasodilation studies via reactive hyperemia or hypercapnia (i.e. 10 mmHg increase in end-tidal carbon dioxide [PetCO2)]). During both studies changes in brachial artery diameter were recorded using continuous ultrasound imaging. Heart rate (HR) was measured throughout both tests. Resting HR (63  ±  11 versus 68  ±  14 beats min−1, p  =  0.0027) and baseline brachial artery diameter measurements (4.57  ±  1.51 versus 5.28  ±  1.86 mm, p  =  0.022) were significantly different between reactive hyperemia and hypercapnia, respectively. HR at peak dilation (65  ±  11 versus 76  ±  14 beats min−1, p  <  0.0001), peak vessel dilation (8.68  ±  4.50 versus 5.28  ±  1.86%, p  =  0.002), and time to peak dilation (90.8  ±  120.1 versus 658.3  ±  226.6 s, p  <  0.0001) were also significantly different between reactive hyperemia and hypercapnia. The dynamics by which reactive hyperemia and hypercapnia stimulate vasodilation appear to differ. Hypercapnia produces a smaller and slower vasodilatory effect than reactive hyperemia. Further research is necessary to better understand the mechanisms of vasodilation under hypercapnic conditions. [ABSTRACT FROM AUTHOR]

Fatty acid esters of hydroxy fatty acid (FAHFA) are anti-diabetic and anti-inflammatory lipokines. Recently FAHFAs were also found to predict cardiorespiratory fitness in a cross-sectional study of recreationally trained runners. Here we report the influences of body composition and gender on static FAHFA abundances in circulation. We compared the association between circulating FAHFA concentrations and body composition, determined by dual x-ray absorptiometry, in female recreational runners who were lean (BMI < 25 kg/m2, n = 6), to those who were overweight (BMI ≥ 25 kg/m2, n = 7). To characterize the effect of gender we also compared circulating FAHFAs in lean male recreational runners (n = 8) to recreationally trained lean female (n = 6) runner group. Circulating FAHFAs were increased in females in a manner that was modulated by specific adipose depot sizes, blood glucose, and lean body mass. As expected, circulating FAHFAs were diminished in the overweight group, but strikingly, within the lean cohort, increases in circulating FAHFAs were promoted by increased fat mass, relative to lean mass, while the overweight group showed a significantly attenuated relationship. These studies suggest multimodal regulation of circulating FAHFAs and raise hypotheses to test endogenous FAHFA dynamic sources and sinks in health and disease, which will be essential for therapeutic target development. Baseline circulating FAHFA concentrations could signal sub-clinical metabolic dysfunction in metabolically healthy obesity.

Corey J Huck1, Ulf G Bronas1, Eric B Williamson1, Christopher C Draheim1, Daniel A Duprez2, Donald R Dengel1,31School of Kinesiology, University of Minnesota, Minneapolis, MN, USA; 2Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN; 3Research Service, Minneapolis Veterans Affairs Medical Center, Minneapolis, MN, USABackground: Many noninvasive arterial assessment techniques have been developed, measuring different parameters of arterial stiffness and endothelial function. However, there is little data available comparing different devices within the same subject. Therefore, the purpose of this study was to examine the repeatability and interrelationships between 3 different techniques to measure arterial stiffness and to compare this with forearm-mediated dilation.Methods: Carotid-radial pulse wave velocity was measured by the Sphygmocor (SPWV) and Complior (CPWV) devices, cardio-ankle vascular index (CAVI) was measured by the VaSera device, vascular structure and function was assessed using ultrasonography and evaluated for reliability and compared in 20 apparently healthy, college-aged men and women.Results: The intraclass correlation coefficient and standard error of the mean for the Sphygmocor (R = 0.56, SEM = 0.69), Complior (R = 0.62, SEM = 0.69), and VaSera (R = 0.60, SEM = 0.56), indicated moderate repeatability. Bland-Altman plots indicated a mean difference of 0.11 ± 0.84 for SPWV, 0.13 ± 1.15 for CPWV, and –0.43 ± 0.90 for CAVI. No significant interrelationships were found among the ultrasound measures and SPWV, CPWV, and CAVI.Conclusions: The three noninvasive modalities to study arterial stiffness reliably measures arterial stiffness however, they do not correlate with ultrasound measures of vascular function and structure in young and apparently healthy subjects.Keywords: Pulse wave velocity, intima-media thickness, flow-mediated dilation