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Endothelial dysfunction and low-grade inflammation in the transition to renal replacement therapy.
Gennip, ACEV, Broers, NJH, Meulen, KJT, Canaud, B, Christiaans, MHL, Cornelis, T, Gelens, MACJ, Hermans, MMH, Konings, CJAM, Net, JBV, et al
PloS one. 2019;(9):e0222547
Abstract
INTRODUCTION End-stage renal disease (ESRD) strongly associates with cardiovascular disease (CVD) risk. This risk is not completely mitigated by renal replacement therapy. Endothelial dysfunction (ED) and low-grade inflammation (LGI) may contribute to the increased CVD risk. However, data on serum biomarkers of ED and LGI during the transition to renal replacement therapy (dialysis and kidney transplantation) are scarce. METHODS We compared serum biomarkers of ED and LGI between 36 controls, 43 participants with chronic kidney disease (CKD) stage 5 non-dialysis (CKD5-ND), 20 participants with CKD stage 5 hemodialysis (CKD5-HD) and 14 participants with CKD stage 5 peritoneal dialysis (CKD5-PD). Further, in 34 and 15 participants repeated measurements were available during the first six months following dialysis initiation and kidney transplantation, respectively. Serum biomarkers of ED (sVCAM-1, E-selectin, P-selectin, thrombomodulin, sICAM-1, sICAM-3) and LGI (hs-CRP, SAA, IL-6, IL-8, TNF-α) were measured with a single- or multiplex array detection system based on electro-chemiluminescence technology. RESULTS In linear regression analyses adjusted for potential confounders, participants with ESRD had higher levels of most serum biomarkers of ED and LGI than controls. In addition, in CKD5-HD levels of serum biomarkers of ED and LGI were largely similar to those in CKD5-ND. In contrast, in CKD5-PD levels of biomarkers of ED were higher than in CKD5-ND and CKD5-HD. Similarly, in linear mixed model analyses sVCAM-1, thrombomodulin, sICAM-1 and sICAM-3 increased after PD initiation. In contrast, incident HD patients showed an increase in sVCAM-1, P-selectin and TNF-α, but a decline of hs-CRP, SAA and IL-6. Further, following kidney transplantation sVCAM-1, thrombomodulin, sICAM-3 and TNF-α were lower at three months post-transplantation and remained stable in the three months thereafter. CONCLUSIONS Levels of serum biomarkers of ED and LGI were higher in ESRD as compared with controls. In addition, PD initiation and, less convincingly, HD initiation may increase levels of selected serum biomarkers of ED and LGI on top of uremia per se. In contrast to dialysis, several serum biomarkers of ED and LGI markedly declined following kidney transplantation.
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Obesity impairs leukocyte-endothelium cell interactions and oxidative stress in humans.
López-Domènech, S, Bañuls, C, Díaz-Morales, N, Escribano-López, I, Morillas, C, Veses, S, Orden, S, Álvarez, Á, Víctor, VM, Hernández-Mijares, A, et al
European journal of clinical investigation. 2018;(8):e12985
Abstract
BACKGROUND To evaluate the relationship between leukocyte-endothelial cell interactions and oxidative stress parameters in non-diabetic patients with different grades of obesity. MATERIAL AND METHODS For this cross-sectional study, 225 subjects were recruited from January 1, 2014 to December 31, 2016 and divided into groups according to BMI (<30 kg/m2 , 30-40 kg/m2 and >40 kg/m²). We determined clinical parameters, systemic inflammatory markers, soluble cellular adhesion molecules, leukocyte-endothelium cell interactions-rolling flux, velocity and adhesion-, oxidative stress parameters-total ROS, total superoxide, glutathione-and mitochondrial membrane potential in leukocytes. RESULTS We verified that HOMA-IR and hsCRP increased progressively as obesity developed, whereas A1c, IL6 and TNFα were augmented in the BMI > 40 kg/m² group. The cellular adhesion molecule sP-selectin was increased in patients with obesity, while sICAM, total ROS, total superoxide and mitochondrial membrane potential were selectively higher in the BMI > 40 kg/m² group. Obesity induced a progressive decrease in rolling velocity and an enhancement of rolling flux and leukocyte adhesion. CONCLUSION Our findings reveal that endothelial dysfunction markers are altered in human obesity and are associated with proinflammatory cytokines and increased oxidative stress parameters.
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Angiogenesis mediators in women with idiopathic heavy menstrual bleeding.
Elkilani, OA, Soliman, MA
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2017;(3):280-284
Abstract
OBJECTIVE To assess the relationship between stromal cell-derived factor 1 (SDF-1) and mature endothelial cells in patients with heavy menstrual bleeding (HMB). METHODS In a prospective observational study, women with idiopathic HMB and control individuals attending Menoufia University Hospital, Egypt, between August 2015 and January 2016 were enrolled. The inclusion criteria were a regular menstrual cycle, a normal coagulation study, and no anomalous ultrasonographic or hysteroscopic findings. Blood samples were collected during different phases of the menstrual cycle (day 5, ovulation, day 24) for measurement of the SDF-1 plasma level (by enzyme-linked immunosorbent assay) and for quantification of mature endothelial cells (by flow cytometry). RESULTS Overall, 20 women with HMB and 10 control individuals were enrolled. The SDF-1 level was significantly lower in the HMB group than in the control group during all phases of the menstrual cycle (P≤0.05 for all). The percentage of mature endothelial cells was significantly higher in the HMB group than among controls (P<0.001 for all). The SDF-1 level and the percentage of endothelial cells were negatively correlated throughout the cycle (P<0.001 for all). CONCLUSION Some mediators of angiogenesis, such as SDF-1 and endothelial cells, are disturbed in women with idiopathic HMB.
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Involvement of leucocyte/endothelial cell interactions in anorexia nervosa.
Víctor, VM, Rovira-Llopis, S, Saiz-Alarcón, V, Sangüesa, MC, Rojo-Bofill, L, Bañuls, C, de Pablo, C, Álvarez, Á, Rojo, L, Rocha, M, et al
European journal of clinical investigation. 2015;(7):670-8
Abstract
BACKGROUND Anorexia nervosa is a common psychiatric disorder in adolescence and is related to cardiovascular complications. Our aim was to study the effect of anorexia nervosa on metabolic parameters, leucocyte-endothelium interactions, adhesion molecules and proinflammatory cytokines. MATERIALS AND METHODS This multicentre, cross-sectional, case-control study employed a population of 24 anorexic female patients and 36 controls. We evaluated anthropometric and metabolic parameters, interactions between leucocytes polymorphonuclear neutrophils (PMN) and human umbilical vein endothelial cells (HUVEC), proinflammatory cytokines such as tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and soluble cellular adhesion molecules (CAMs) including E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). RESULTS Anorexia nervosa was related to a decrease in weight, body mass index, waist circumference, systolic blood pressure, glucose, insulin and HOMA-IR, and an increase in HDL cholesterol. These effects disappeared after adjusting for BMI. Anorexia nervosa induced a decrease in PMN rolling velocity and an increase in PMN rolling flux and PMN adhesion. Increases in IL-6 and TNF-α and adhesion molecule VCAM-1 were also observed. CONCLUSIONS This study supports the hypothesis of an association between anorexia nervosa, inflammation and the induction of leucocyte-endothelium interactions. These findings may explain, in part at least, the increased risk of vascular disease among patients with anorexia nervosa.
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Electronegative low-density lipoprotein increases C-reactive protein expression in vascular endothelial cells through the LOX-1 receptor.
Chu, CS, Wang, YC, Lu, LS, Walton, B, Yilmaz, HR, Huang, RY, Sawamura, T, Dixon, RA, Lai, WT, Chen, CH, et al
PloS one. 2013;(8):e70533
Abstract
OBJECTIVES Increased plasma C-reactive protein (CRP) levels are associated with the occurrence and severity of acute coronary syndrome. We investigated whether CRP can be generated in vascular endothelial cells (ECs) after exposure to the most electronegative subfraction of low-density lipoprotein (LDL), L5, which is atherogenic to ECs. Because L5 and CRP are both ligands for the lectin-like oxidized LDL receptor-1 (LOX-1), we also examined the role of LOX-1. METHODS AND RESULTS Plasma LDL samples isolated from asymptomatic hypercholesterolemic (LDL cholesterol [LDL-C] levels, 154.6±20 mg/dL; n = 7) patients and normocholesterolemic (LDL-C levels, 86.1±21 mg/dL; P<0.001; n = 7) control individuals were chromatographically resolved into 5 subfractions, L1-L5. The L5 percentage (L5%) and the plasma L5 concentration ([L5] = L5% × LDL-C) in the patient and control groups were 8.1±2% vs. 2.3±1% (P<0.001) and 12.6±4 mg/dL vs. 1.9±1 mg/dL (P<0.001), respectively. In hypercholesterolemic patients treated with atorvastatin for 6 months (10 mg/day), [L5] decreased from 12.6±4 mg/dL to 4.5±1.1 mg/dL (P = 0.011; n = 5), whereas both [L5] and L5% returned to baseline levels in 2 noncompliant patients 3 months after discontinuation. In cultured human aortic ECs (HAECs), L5 upregulated CRP expression in a dose- and time-dependent manner up to 2.5-fold (P<0.01), whereas the least electronegative subfraction, L1, had no effect. DiI-labeled L1, internalized through the LDL receptor, became visible inside HAECs within 30 seconds. In contrast, DiI-labeled L5, internalized through LOX-1, became apparent after 5 minutes. L5-induced CRP expression manifested at 30 minutes and was attenuated by neutralizing LOX-1. After 30 minutes, L5 but not L1 induced reactive oxygen species (ROS) production. Both L5-induced ROS and CRP production were attenuated by ROS inhibitor N-acetyl cysteine. CONCLUSIONS Our results suggest that CRP, L5, and LOX-1 form a cyclic mechanism in atherogenesis and that reducing plasma L5 levels with atorvastatin disrupts the vascular toxicity of L5.