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Is There Association between Altered Adrenergic System Activity and Microvascular Endothelial Dysfunction Induced by a 7-Day High Salt Intake in Young Healthy Individuals.
Stupin, A, Drenjančević, I, Šušnjara, P, Debeljak, Ž, Kolobarić, N, Jukić, I, Mihaljević, Z, Martinović, G, Selthofer-Relatić, K
Nutrients. 2021;(5)
Abstract
This study aimed to test the effect of a 7-day high-salt (HS) diet on autonomic nervous system (ANS) activity in young healthy individuals and modulation of ANS on microvascular endothelial function impairment. 47 young healthy individuals took 7-day low-salt (LS) diet (3.5 g salt/day) followed by 7-day high-salt (HS) diet (~14.7 g salt/day). ANS activity was assessed by 24-h urine catecholamine excretion and 5-min heart rate variability (HRV). Skin post-occlusive reactive hyperemia (PORH) and acetylcholine-induced dilation (AChID) were assessed by laser Doppler flowmetry (LDF). Separately, mental stress test (MST) at LS and HS condition was conducted, followed by immediate measurement of plasma metanephrines' level, 5-min HRV and LDF microvascular reactivity. Noradrenaline, metanephrine and normetanephrine level, low-frequency (LF) HRV and PORH and AChID significantly decreased following HS compared to LS. MST at HS condition tended to increase HRV LF/HF ratio. Spectral analysis of PORH signal, and AChID measurement showed that MST did not significantly affect impaired endothelium-dependent vasodilation due to HS loading. In this case, 7-day HS diet suppressed sympathetic nervous system (SNS) activity, and attenuated microvascular reactivity in salt-resistant normotensive individuals. Suppression of SNS during HS loading represents a physiological response, rather than direct pathophysiological mechanism by which HS diet affects microvascular endothelial function in young healthy individuals.
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Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: A cross-sectional observational study.
Martens, RJH, Broers, NJH, Canaud, B, Christiaans, MHL, Cornelis, T, Gauly, A, Hermans, MMH, Konings, CJAM, van der Sande, FM, Scheijen, JLJM, et al
PloS one. 2019;(8):e0221058
Abstract
BACKGROUND Cardiovascular disease (CVD) related mortality and morbidity are high in end-stage renal disease (ESRD). The pathophysiology of CVD in ESRD may involve non-traditional CVD risk factors, such as accumulation of advanced glycation endproducts (AGEs), dicarbonyls, endothelial dysfunction (ED) and low-grade inflammation (LGI). However, detailed data on the relation of AGEs and dicarbonyls with ED and LGI in ESRD are limited. METHODS We examined cross-sectional Spearman's rank correlations of AGEs and dicarbonyls with serum biomarkers of ED and LGI in 43 individuals with chronic kidney disease (CKD) stage 5 not on dialysis (CKD5-ND). Free and protein-bound serum AGEs (N∈-(carboxymethyl)lysine (CML), N∈-(carboxyethyl)lysine (CEL), Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)) and serum dicarbonyls (glyoxal, methylglyoxal, 3-deoxyglucosone) were analyzed with tandem mass spectrometry, and tissue AGE accumulation was estimated by skin autofluorescence (SAF). Further, serum biomarkers of ED and LGI included sVCAM-1, sE-selectin, sP-selectin, sThrombomodulin, sICAM-1, sICAM-3, hs-CRP, SAA, IL-6, IL-8 and TNF-α. RESULTS After adjustment for age, sex and diabetes status, protein-bound CML was positively correlated with sVCAM-1; free CEL with sVCAM-1 and sThrombomodulin; glyoxal with sThrombomodulin; and methylglyoxal with sVCAM-1 (correlation coefficients ranged from 0.36 to 0.44). In addition, free CML was positively correlated with SAA; protein-bound CML with IL-6; free CEL with hs-CRP, SAA and IL-6; free MG-H1 with SAA; protein-bound MG-H1 with IL-6; and MGO with hs-CRP and IL-6 (correlation coefficients ranged from 0.33 to 0.38). Additional adjustment for eGFR attenuated partial correlations of serum AGEs and serum dicarbonyls with biomarkers of ED and LGI. CONCLUSIONS In individuals with CKD5-ND, higher levels of serum AGEs and serum dicarbonyls were related to biomarkers of ED and LGI after adjustment for age, sex and diabetes mellitus. Correlations were attenuated by eGFR, suggesting that eGFR confounds and/or mediates the relation of serum AGEs and dicarbonyls with ED and LGI.
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Correlations Between Serum Cholesterol and Vascular Lesions in Fabry Disease Patients.
Katsuta, H, Tsuboi, K, Yamamoto, H, Goto, H
Circulation journal : official journal of the Japanese Circulation Society. 2018;(12):3058-3063
Abstract
BACKGROUND Fabry disease is an X-linked lysosomal storage disorder and shows globotriosylceramide (Gb3) accumulation in multiple organs, resulting from a deficiency of α-galactosidase. In patients with Fabry disease, cardiovascular disease occurs at an early age. Previous studies have shown that serum levels of high-density lipoprotein-cholesterol (HDL-C) increase in this disease, yet its clinical significance for cardiovascular disease remains unclear. Methods and Results: In order to determine why the serum HDL-cholesterol is high in various cardiovascular diseases of Fabry disease patients, we evaluated the serum lipid profiles, ocular vascular lesions, and levels of serum vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 in 69 patients with Fabry disease diagnosed by genetic examination. The serum HDL-C/total cholesterol (T-Chol) ratio was significantly high, especially in male patients (41.5±1.7%) regardless of body mass index. Ocular vascular lesions were more likely to occur in female patients with a high HDL-C/T-Chol ratio compared with most male patients. Female patients with a high HDL-C/T-Chol ratio also presented a high serum VEGF level, suggesting that vascular endothelium dysfunction and arteriosclerotic changes progress more severely than in patients with a normal HDL-C/T-Chol ratio. In most patients, enzyme replacement therapy improved serum Gb3 and lyso-Gb3 levels, but these Gb3 and lyso-Gb3 still remained higher than in healthy controls, which appears to result in continuous vascular arteriosclerotic changes. CONCLUSIONS We concluded that increased low-density lipoprotein-cholesterol uptake to the vascular wall caused by endothelial dysfunction is likely to contribute to the high HDL-C/T-Chol ratio observed in Fabry disease patients.
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Impact of single anaerobic exercise on delayed activation of endothelial xanthine oxidase in men and women.
Wiecek, M, Maciejczyk, M, Szymura, J, Kantorowicz, M, Szygula, Z
Redox report : communications in free radical research. 2017;(6):367-376
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Abstract
OBJECTIVES The aim of the study was to evaluate the activity of xanthine oxidase (XO) in the blood of men and women during the first hour following a single anaerobic exercise (AN-EX), and after 24 hours of recovery, and to determine whether the changes in XO activity in the blood after AN-EX are dependent on anaerobic performance. METHODS Ten men and ten women performed a single AN-EX. Blood was collected before and five times after completion of the AN-EX. The activity of XO was determined. RESULTS In both groups, a significant (P < 0.05) increase in blood XO activity was found only 24 hours after the AN-EX. The increased activity of XO in men was significantly lower than in women (P < 0.05). Negative correlations were found between the increase in XO activity in the blood plasma 24 hours after the AN-EX and anaerobic power, the total work performed during the AN-EX and the power decrease. DISCUSSION In the first hour after the single AN-EX, XO activity in the blood of women and men did not change, but after 24 hours of recovery, it was significantly higher compared to baseline levels in both sexes. Single AN-EX causes a smaller increase in XO activity in people with higher anaerobic performance.
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Effect of Regular Aerobic Activity in Young Healthy Athletes on Profile of Endothelial Function and Platelet Activity.
Podgórska, K, Derkacz, A, Szahidewicz-Krupska, E, Jasiczek, J, Dobrowolski, P, Radziwon-Balicka, A, Skomro, R, Szuba, A, Mazur, G, Doroszko, A
BioMed research international. 2017;:8715909
Abstract
The aim of the study was to assess the impact of regular professional sports activity on the endothelial and platelet function in young men. The studied group were 79 young men (18-40 y, 25 athletes and 54 without any regular physical activity). The nitric oxide (NO) metabolic pathway intermediates, oxidative stress markers, mediators of inflammation, and platelet aggregation were measured. Flow mediated dilation (FMD) was studied before and after intravenous 16,0 g L-arginine infusion, which was repeated after oral administration of acetylsalicylic acid (ASA-75 mg/day) for 4 days. Both groups had similar demographic characteristics. In the athletes, there was significantly higher hsCRP level, better serum lipid profile, and lower pulse pressure. Greater baseline FMD in athletes and in response to L-arginine disappeared following ASA treatment. There were no differences in the levels of the NO pathway metabolites. The control group was characterized by higher PAI-1 following ASA treatment and sICAM-1 both at baseline and after ASA, but no differences in MDA and 6-keto-PGF-1 alpha and platelet aggregation were noted. Regular professional physical activity modulates endothelial but not platelet function and may thus exert an effect on overall cardiovascular risk.
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Evaluation of microvascular endothelial function in patients with infective endocarditis using laser speckle contrast imaging and skin video-capillaroscopy: research proposal of a case control prospective study.
Barcelos, A, Lamas, C, Tibiriça, E
BMC research notes. 2017;(1):342
Abstract
OBJECTIVE Infective endocarditis is a severe condition with high in-hospital and 5-year mortality. There is increasing incidence of infective endocarditis, which may be related to healthcare and changes in prophylaxis recommendations regarding oral procedures. Few studies have evaluated the microcirculation in patients with infective endocarditis, and so far, none have utilized laser-based technology or evaluated functional capillary density. The aim of the study is to evaluate the changes in the systemic microvascular bed of patients with both acute and subacute endocarditis. This is a cohort study that will include adult patients with confirmed active infective endocarditis according to the modified Duke criteria who were admitted to our center for treatment. A control group of sex- and age-matched healthy volunteers will be included. Functional capillary density, which is defined as the number of spontaneously perfused capillaries per square millimeter of skin, will be assessed by video-microscopy with an epi-illuminated fiber optic microscope. Capillary recruitment will be evaluated using post-occlusive reactive hyperemia. Microvascular flow will be evaluated in the forearm using a laser speckle contrast imaging system for the noninvasive and continuous measurement of cutaneous microvascular perfusion changes. Laser speckle contrast imaging will be used in combination with skin iontophoresis of acetylcholine, an endothelium-dependent vasodilator, or sodium nitroprusside (endothelium independent) to test microvascular reactivity. RESULTS The present study will contribute to the investigation of microcirculatory changes in infective endocarditis and possibly lead to an earlier diagnosis of the condition and/or determination of its severity and complications. Trial registration ClinicalTrials.gov ID: NCT02940340.
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Clopidogrel Improves Skin Microcirculatory Endothelial Function in Persons With Heightened Platelet Aggregation.
Salimi, S, Lewis, JP, Yerges-Armstrong, LM, Mitchell, BD, Saeed, F, O'Connell, JR, Perry, JA, Ryan, KA, Shuldiner, AR, Parsa, A
Journal of the American Heart Association. 2016;(11)
Abstract
BACKGROUND Platelet activation can lead to enhanced oxidative stress, inflammatory response, and endothelial dysfunction. To quantify the effects of platelet inhibition on endothelial function, we assessed platelet activity of healthy persons before and after clopidogrel administration and evaluated its effects on endothelial function. We hypothesized that clopidogrel, by attenuating platelet activity, would result in enhanced endothelial function. METHODS AND RESULTS Microcirculatory endothelial function was quantified by laser Doppler flowmetry (LDF) mediated by thermal hyperemia (TH) and postocclusive reactive hyperemia, respectively, in 287 and 241 relatively healthy and homogenous Old Order Amish persons. LDF and platelet aggregation measures were obtained at baseline and after 7 days of clopidogrel administration. Our primary outcome was percentage change in post- versus preclopidogrel LDF measures. Preclopidogrel TH-LDF and platelet aggregation were higher in women than in men (P<0.001). Clopidogrel administration was associated with ≈2-fold higher percentage change in TH-LDF in participants with high versus low baseline platelet aggregation (39.4±10.1% versus 17.4±5.6%, P=0.03). Clopidogrel also increased absolute TH-LDF measures in persons with high platelet aggregation (1757±766 to 2154±1055, P=0.03), with a more prominent effect in women (1909±846 to 2518±1048, P=0.001). There was no evidence that clopidogrel influenced postocclusive reactive hyperemia LDF measures. CONCLUSIONS The administration of clopidogrel in healthy persons with high baseline platelet aggregation results in improved TH-induced microcirculatory endothelial function. These data suggest that clopidogrel may have a beneficial effect on microcirculatory endothelial function, presumably through antiplatelet activity, and may confer additional vascular benefits. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT00799396.
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Effect of vitamin D3 treatment on endothelial function in obese adolescents.
Javed, A, Kullo, IJ, Balagopal, PB, Kumar, S
Pediatric obesity. 2016;(4):279-84
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BACKGROUND Obesity in children is associated with vitamin D deficiency and endothelial dysfunction. It is not known if treatment with vitamin D improves endothelial function in obese adolescents. OBJECTIVE This study aimed to determine whether treatment with vitamin D3 improves endothelial function in obese adolescents. METHODS Nineteen obese adolescents, 13-18 years of age, with 25-hydroxy vitamin D (25[OH]D) levels <75 nmol L(-1) were treated with 100 000 IU vitamin D3 orally once a month for 3 months in an open-label, single-centre prospective trial. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery at study entry and 1 month after the third dose of vitamin D3 . Biochemical parameters, including calcium, fasting lipids, glucose, insulin and high-sensitivity C-reactive protein, were also obtained. RESULTS Mean 25(OH)D levels increased from 55.9 ± 12.2 to 86.9 ± 16.7 nmol L(-1) (P < 0.01). There was no correlation between 25(OH)D levels and brachial artery FMD. The brachial artery FMD (%) did not change significantly following vitamin D3 treatment (9.5 ± 3.53 vs. 10.3 ± 3.83, P = 0.83). Serum parathyroid hormone declined from 3.8 ± 1.5 to 3.1 ± 1 pmol L(-1) (P = 0.01). The remainder of biochemical measurements did not show a significant change. CONCLUSIONS Treatment with vitamin D3 , 100 000 IU once a month for 3 months was effective in increasing 25(OH)D levels in obese adolescents but did not impact endothelial function.
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Plasma ADMA associates with all-cause mortality in renal transplant recipients.
Frenay, AR, van den Berg, E, de Borst, MH, Beckmann, B, Tsikas, D, Feelisch, M, Navis, G, Bakker, SJ, van Goor, H
Amino acids. 2015;(9):1941-9
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Abstract
Asymmetric dimethylarginine (ADMA) is a key endogenous inhibitor of endothelial NO synthase that affects endothelial function, blood pressure and vascular remodeling. Increased plasma levels of ADMA are associated with worse outcome from cardiovascular disease. Due to endothelial dysfunction before and after kidney transplantation, renal transplant recipients (RTR) are at high risk for the alleged deleterious effects of ADMA. We investigated the associations of ADMA levels with all-cause mortality and graft failure in RTR. Plasma ADMA levels were determined in 686 stable outpatient RTR (57 % male, 53 ± 13 years), with a functioning graft for ≥1 year. Determinants of ADMA were evaluated with multivariate linear regression models. Associations between ADMA and mortality were assessed using multivariable Cox regression analyses. The strongest associations with plasma ADMA in the multivariable analyses were male gender, donor age, parathyroid hormone, NT-pro-BNP and use of calcium supplements. During a median follow-up of 3.1 [2.7-3.9] years, 79 (12 %) patients died and 45 (7 %) patients developed graft failure. ADMA was associated with increased all-cause mortality [HR 1.52 (95 % CI 1.26-1.83] per SD increase, P < 0.001], whereby associations remained upon adjustment for confounders. ADMA was associated with graft failure [HR 1.41 (1.08-1.83) per SD increase, P = 0.01]; however, upon addition of eGFR significance was lost. High levels of plasma ADMA are associated with increased mortality in RTR. Our findings connect disturbed NO metabolism with patient survival after kidney transplantation.
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Coronary Endothelial Dysfunction in Women With Type 2 Diabetes Measured by Coronary Phase Contrast Flow Velocity Magnetic Resonance Imaging.
Maroules, CD, Chang, AY, Kotys-Traughber, MS, Peshock, RM
Journal of investigative medicine : the official publication of the American Federation for Clinical Research. 2015;(7):856-61
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OBJECTIVE The aim of this study was to determine if differences in coronary endothelial function are observed between asymptomatic women with type 2 diabetes mellitus (DM) and control subjects using coronary phase contrast flow velocity magnetic resonance imaging in response to cold pressor stress, an established endothelium-dependent vasodilatory stress. METHODS Phase contrast flow velocity imaging of the right coronary artery was performed in 7 asymptomatic premenopausal women with DM and 8 healthy female participants in response to the cold pressor test at 3 T. RESULTS There was no significant difference in percent increase in coronary flow velocity from rest to peak flow velocity between DM and control subjects (32% ± 22% vs 46% ± 17%; P = 0.11). However, percent increase in coronary flow velocity was lower in DM than in control subjects (-3% ± 14% vs 31% ± 30%; P = 0.01) during the second minute of cold pressor stress, when endothelial-mediated vasodilation should occur. CONCLUSIONS Asymptomatic women with DM demonstrate reduced coronary flow velocity during the second minute of cold pressor stress, indicating coronary endothelial dysfunction.