scholarly journals FRI0453 COMPARATIVE GENE PROFILE IN MONOCYTES FROM CHILDHOOD- AND ADULT-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS: CLUES TO DIFFERENT SYSTEMIC INVOLVEMENT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 823.2-824
Author(s):  
I. C. Aranda-Valera ◽  
A. M. Patiño-Trives ◽  
R. M. Rosa ◽  
M. A. Aguirre ◽  
P. S. Laura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Lupus Erythematosus ◽  
Association Studies ◽  
Atherogenic Index ◽  
Molecular Profile ◽  
Research Support ◽  
Systemic Involvement ◽  
Dsdna Antibodies ◽  
And Oxidative Stress

Background:Objectives:1. This study, developed within the Innovative Medicines Initiative Joint Undertaking project PRECISESADS framework, aimed at identify specific inflammatory and oxidative stress determinants involved in the enhanced CV-risk present in SLE patients and to analyze the relevance of the sustained positivity for anti-dsDNA on the establishment of their atherothrombotic status.Methods:One hundred and twenty-four SLE consecutive patients (not including patients with associated antiphospholipid syndrome), belonging to the PRECISESADS project, were evaluated for the presence of CVD and its association with positivity for anti-dsDNA antibodies. A second cohort of 62 SLE patients was included, of which endothelial dysfunction, lipid profile, the presence of atheroma plaques (identified by a pathologic increase in the carotid intimae media thickness -CIMT-), and the frequencies of anti-dsDNA positivity for 7 years, were evaluated. Serum inflammatory and oxidative stress biomolecules, and NETosis-derived bioproducts were further evaluated by multiplex assay and specific commercial kits, respectively. Besides, miRNnomes were identified using next-generation sequencing. Clinical significance of the biomolecules analyzed was explored by correlation/association studies with immunological and CV-risk features.Results:A significant relationship among the incidence of CVD (i.e. thrombosis or cardiac involvement) and the positivity for anti-dsDNA antibodies was recognized in the first SLE cohort. Accordingly, in the second SLE cohort, significantly impaired micro-vascular endothelial function (identified by reduction of hyperemia post-occlusion area), increased atherogenic index and pathologic increase in the CIMT were assessed in patients positive for anti-dsDNA in relation to anti-dsDNA negative patients. Around a 65% of SLE patients displayed a sustained positivity for anti-dsDNA antibodies for more than 7 years. These patients showed a distinctive and specific molecular profile compared with patients that had remained negative for anti-dsDNA, including increased inflammatory profile (IL1B, IL2, IL6, IL17, EOTAXIN, FGF, GMCSF, IFNγ, IP10, RANTES, TNF), enhanced oxidative status (lipoperoxides), and higher NETosis (nucleosomes, elastase). Levels of those biomolecules were closely interconnected and associated to their regulatory miRNAs, which accordingly exhibited differential expression in SLE anti-dsDNA(+)vsanti-dsDNA(-) patients. Finally, the frequency for positivity of anti-dsDNA significantly correlated both with markers of endothelial dysfunction and with the presence of atheroma plaques in SLE patients, pointing at the direct involvement of anti-dsDNA-Abs in the development of these processes.Conclusion:1. Positivity for anti-dsDNA antibodies confers a specific inflammatory/oxidative profile linked to an enhanced CV-risk in SLE patients. 2. Moreover, the sustained positivity for anti-dsDNA antibodies fosters the establishment of an atherothrombotic status in these autoimmune patients.Acknowledgments:Supported by the EU/EFPIA –IMI-JU PRECISESADS (n° 115565) and ISCIII (PI18/0837 and RIER RD16/0012/0015), Co-funded with FEDER.Disclosure of Interests:Inmaculada Concepcion Aranda-Valera: None declared, Alejandra M. Patiño-Trives: None declared, Roldán Molina Rosa: None declared, Maria A Aguirre: None declared, Pérez Sánchez Laura: None declared, Carlos Pérez Sánchez: None declared, María Luque-Tévar: None declared, Iván Arias de la Rosa: None declared, Maria del Carmen Abalos-Aguilera: None declared, Desiree Ruíz-Vilchez: None declared, Mario Espinosa: None declared, Nuria Barbarroja Puerto Grant/research support from: ROCHE and Pfizer., Speakers bureau: ROCHE and Celgene., Eduardo Collantes-Estévez Grant/research support from: ROCHE and Pfizer., Speakers bureau: ROCHE, Lilly, Bristol and Celgene., Chary Lopez-Pedrera Grant/research support from: ROCHE and Pfizer.

scholarly journals AB0136 THE SUSTAINED POSITIVITY FOR ANTI-DSDNA ANTIBODIES FOSTERS THE ESTABLISHMENT OF AN ATHEROTHROMBOTIC STATUS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1368.2-1369
Author(s):  
A. M. Patiño-Trives ◽  
M. A. Aguirre ◽  
C. Pérez Sánchez ◽  
P. S. Laura ◽  
M. Luque-Tévar ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Lupus Erythematosus ◽  
Association Studies ◽  
Atherogenic Index ◽  
Molecular Profile ◽  
Vascular Endothelial ◽  
Research Support ◽  
Inflammatory Profile ◽  
Commercial Kits ◽  
Dsdna Antibodies

Background:Objectives:1. This study, developed within the Innovative Medicines Initiative Joint Undertaking project PRECISESADS framework, aimed to identify specific molecular profiles involved in the enhanced CV-risk present in SLE patients and to analyze the relevance of the sustained positivity for anti-dsDNA on the establishment of their atherothrombotic status.Methods:One hundred and twenty-four SLE consecutive patients (not including patients with associated antiphospholipid syndrome), belonging to the PRECISESADS project, were evaluated for the presence of CVD and its association with positivity for anti-dsDNA antibodies. A second cohort of 62 SLE patients was included, of which endothelial dysfunction, lipid profile, the presence of atheroma plaques (identified by a pathologic increase in the carotid intimae media thickness -CIMT-), and the frequencies of anti-dsDNA positivity for 7 years, were evaluated. Serum inflammatory and oxidative stress biomolecules, and NETosis-derived bioproducts were further evaluated by multiplex assay and specific commercial kits, respectively. Besides, miRNnomes were identified using next-generation sequencing. Clinical significance of the biomolecules analyzed was explored by correlation/association studies with immunological and CV-risk features.Results:A significant relationship among the incidence of CVD (i.e. thrombosis or cardiac involvement) and the positivity for anti-dsDNA antibodies was recognized in the first SLE cohort. Accordingly, in the second SLE cohort, significantly impaired micro-vascular endothelial function (identified by reduction of hyperemia post-occlusion area), increased atherogenic index and pathologic increase in the CIMT were assessed in patients positive for anti-dsDNA in relation to anti-dsDNA negative patients. Around a 65% of SLE patients displayed a sustained positivity for anti-dsDNA antibodies for more than 7 years. These patients showed a distinctive and specific molecular profile compared with patients that had remained negative for anti-dsDNA, including increased inflammatory profile (IL1B, IL2, IL6, IL17, EOTAXIN, FGF, GMCSF, IFNγ, IP10, RANTES, TNF), enhanced oxidative status (lipoperoxides), and higher NETosis (nucleosomes, elastase). Levels of those biomolecules were closely interconnected and associated to their regulatory miRNAs, which accordingly exhibited differential expression in SLE anti-dsDNA(+)vsanti-dsDNA(-) patients. Finally, the frequency for positivity of anti-dsDNA significantly correlated both with markers of endothelial dysfunction and with the presence of atheroma plaques in SLE patients, pointing at the direct involvement of anti-dsDNA-Abs in the development of these processes.Conclusion:1. Positivity for anti-dsDNA antibodies confers a specific molecular profile linked to an enhanced CV-risk in SLE patients. 2. Moreover, the sustained positivity for anti-dsDNA antibodies fosters the establishment of an atherothrombotic status in these autoimmune patients.Acknowledgments:Supported by the EU/EFPIA –IMI-JU PRECISESADS (n° 115565) and ISCIII (PI18/0837 and RIER RD16/0012/0015), Co-funded with FEDER.Disclosure of Interests:Alejandra M. Patiño-Trives: None declared, Maria A Aguirre: None declared, Carlos Pérez Sánchez: None declared, Pérez Sánchez Laura: None declared, María Luque-Tévar: None declared, Iván Arias de la Rosa: None declared, Rafaela Ortega Castro: None declared, Maria del Carmen Abalos-Aguilera: None declared, Mario Espinosa: None declared, Pedro Seguí Azpilcueta: None declared, Jacques-Olivier Pers: None declared, Nuria Barbarroja Puerto Grant/research support from: ROCHE and Pfizer., Speakers bureau: ROCHE and Celgene., Marta Alarcon-Riquelme: None declared, Eduardo Collantes Estevez Grant/research support from: ROCHE and Pfizer, Speakers bureau: ROCHE, Lilly, Bristol and Celgene, Chary Lopez-Pedrera Grant/research support from: ROCHE and Pfizer.

scholarly journals GTP Cyclohydrolase I Gene Polymorphisms Are Associated with Endothelial Dysfunction and Oxidative Stress in Patients with Type 2 Diabetes Mellitus

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e108587 ◽  
Author(s):  
Pawel P. Wolkow ◽  
Wladyslaw Kosiniak-Kamysz ◽  
Grzegorz Osmenda ◽  
Grzegorz Wilk ◽  
Beata Bujak-Gizycka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Gene Polymorphisms ◽  
Gtp Cyclohydrolase I ◽  
And Oxidative Stress ◽  
I Gene

Mercury Exposure and Endothelial Dysfunction

2015 ◽  
Vol 34 (4) ◽  
pp. 300-307 ◽  
Author(s):  
Swati Omanwar ◽  
M. Fahim
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Vascular Endothelium ◽  
Circulatory System ◽  
Vital Role ◽  
Mercury Exposure ◽  
And Function ◽  
The Impact ◽  
And Oxidative Stress

Vascular endothelium plays a vital role in the organization and function of the blood vessel and maintains homeostasis of the circulatory system and normal arterial function. Functional disruption of the endothelium is recognized as the beginning event that triggers the development of consequent cardiovascular disease (CVD) including atherosclerosis and coronary heart disease. There is a growing data associating mercury exposure with endothelial dysfunction and higher risk of CVD. This review explores and evaluates the impact of mercury exposure on CVD and endothelial function, highlighting the interplay of nitric oxide and oxidative stress.

Relationship between atherogenic index and oxidative stress among patients presented with coronary artery disease in a tertiary care hospital

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 2807-2813
Author(s):  
Resmi C R ◽  
Kedari G S R ◽  
Deepa P K
Keyword(s):  
Oxidative Stress ◽  
Vitamin E ◽  
Vitamin C ◽  
Density Lipoprotein ◽  
Atherogenic Index ◽  
Enzymatic Antioxidants ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Lipid Parameters ◽  
And Oxidative Stress

CAD is recognized as a multifactorial disease that is influenced by environmental and genetic factors. This study aimed to evaluate the levels of lipid parameters, oxidative stress and antioxidant markers in subjects with CAD compared to their age & sex matched controls and to analyze the relationship between atherogenic Index and oxidative stress among them 62 clinically proved CAD patients and 62 healthy age and sex matched subjects without CAD were selected for this study. 5 ml of fasting venous blood was collected from all the subjects and investigations such as FPG, lipid profile, oxidative markers Malondialdehyde (MDA), F2 isoprostanes (F2iso) and antioxidants glutathione S-transferase (GST), superoxide dismutase (SOD), vitamin-C, vitamin-E were performed. This study showed that levels of lipid parameters total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c) and AI were significantly higher whereas high density lipoprotein cholesterol (HDL-c) were significantly low in CAD patients compared to normal controls. Oxidative stress markers MDA and F2 Isoprostanes level were significantly high, whereas enzymatic antioxidants GST and SOD and non-enzymatic antioxidants Vitamin-C and Vitamin-E levels were significantly low in CAD patients. Oxidative stress markers were found to significantly influence the AI. Results of this study showed that oxidative stress markers F2iso and MDA and antioxidants GST, VIT-C and VIT-E are found to influence the atherogenic index significantly.

Remote Ischemic Preconditioning Protects Against Endothelial Dysfunction in a Human Model of Systemic Inflammation: A Randomized Clinical Trial

2021 ◽  
Author(s):  
Marco Orlandi ◽  
Stefano Masi ◽  
Devina Bhowruth ◽  
Yago Leira ◽  
Georgios Georgiopoulos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Systemic Inflammation ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Remote Ischemic Preconditioning ◽  
Human Model ◽  
Control Group ◽  
Flow Mediated Dilatation ◽  
And Oxidative Stress

Objective: Inflammation, oxidative stress, and endothelial dysfunction are known to contribute to ischemia-reperfusion injury. Remote ischemic preconditioning (RIPC) protects from endothelial dysfunction and the damage induced by ischemia-reperfusion. Using intensive periodontal treatment (IPT), an established human model of acute systemic inflammation, we investigated whether RIPC prevents endothelial dysfunction and modulates systemic levels of inflammation and oxidative stress. Approach and Results: Forty-nine participants with periodontitis were randomly allocated to receive either 3 cycles of ischemia-reperfusion on the upper limb (N=25, RIPC) or a sham procedure (N=24, control) before IPT. Endothelial function assessed by flow-mediated dilatation of the brachial artery, inflammatory cytokines, markers of vascular injury, and oxidative stress were evaluated at baseline, day 1, and day 7 after IPT. Twenty-four hours post-IPT, the RIPC group had lower levels of IL (interleukin)-10 and IL-12 compared with the control group ( P <0.05). RIPC attenuated the IPT-induced increase in IL-1β, E-selectin, sICAM-3 (soluble intercellular adhesion molecule 3), and s-thrombomodulin levels between the baseline and day 1 ( P for interaction <0.1). Conversely, oxidative stress was differentially increased at day1 in the RIPC group compared with the control group ( P for interaction <0.1). This was accompanied by a better flow-mediated dilatation (mean difference 1.75% [95% CI, 0.428–3.07], P =0.011). After 7 days from IPT, most of the inflammatory markers endothelial-dependent and -independent vasodilation were similar between groups. Conclusions: RIPC prevented acute endothelial dysfunction by modulation of inflammation and oxidation processes in patients with periodontitis following exposure to an acute inflammatory stimulus. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03072342.

scholarly journals The impact of various antihypertensive medications on vascular aging

2021 ◽  
Vol 27 (2) ◽  
pp. 133-145
Author(s):  
E. N. Dudinskaya ◽  
L. V. Matchekhina ◽  
K. A. Eruslanova ◽  
O. A. Dogotar ◽  
L. P. Ryltseva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Pulse Wave ◽  
Antihypertensive Drugs ◽  
Augmentation Index ◽  
Vascular Aging ◽  
Antihypertensive Medications ◽  
The Impact ◽  
Stress Patterns ◽  
And Oxidative Stress

The review summarizes the data of past two decades on the effect of hypertension on vascular aging and considers the effect of chronic inflammation and oxidative stress patterns on the remodeling of cardiovascular system. Clinical studies on the effect of various classes of antihypertensive drugs on age-associated parameters of vascular aging are discussed. These include endothelial dysfunction and arterial assessed by endothelium-dependent vasodilation, pulse wave velocity, augmentation index, cardiovascular index, thickness of the intima-media complex, and so on.

Abstract 357: Hepatic ERK2 Suppresses Endoplasmic Reticulum Stress, Leading to Protection from Oxidative Stress and Endothelial Dysfunction

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Takehiko Kujiraoka ◽  
Yasushi Satoh ◽  
Makoto Ayaori ◽  
Yasunaga Shiraishi ◽  
Yuko Arai-Nakaya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Fatty Acid ◽  
Endothelial Dysfunction ◽  
Er Stress ◽  
Vascular Complications ◽  
Metabolic Remodeling ◽  
And Oxidative Stress

Background Insulin signaling comprises 2 major cascades, the IRS/PI3K/Akt and Ras/Raf/MEK/ERK pathways. Many studies on the tissue-specific effects of the former pathway had been conducted, however, the role of the latter cascade in tissue-specific insulin resistance had not been investigated. High glucose/fatty acid toxicity, inflammation and oxidative stress, all of which are associated with insulin resistance, can activate ERK. Liver plays a central role of metabolism and hepatosteatosis (HST) is associated with vascular diseases. The aim of this study is to elucidate the role of hepatic ERK2 in HST, metabolic remodeling and endothelial dysfunction. Methods Serum biomarkers of vascular complications in human were compared between subjects with and without HST diagnosed by echography for regular medical checkup. Next, we created liver-specific ERK2 knockout mice (LE2KO) and fed them with a high-fat/high-sucrose diet (HFHSD) for 20 weeks. The histological analysis, the expression of hepatic sarco/endoplasmic reticulum (ER) Ca 2+ -ATPase 2 (SERCA2) and glucose-tolerance/insulin-sensitivity (GT/IS) were tested. Vascular superoxide production and endothelial function were evaluated with dihydroethidium staining and isometric tension measurement of aorta. Results The presence of HST significantly increased HOMA-IR, an indicator of insulin resistance or atherosclerotic index in human. HFHSD-fed LE2KO revealed a marked exacerbation in HST and metabolic remodeling represented by the impairment of GT/IS, elevated serum free fatty acid and hyperhomocysteinemia without changes in body weight, blood pressure and serum cholesterol/triglyceride levels. In the HFHSD-fed LE2KO, mRNA and protein expressions of hepatic SERCA2 were significantly decreased, which resulted in hepatic ER stress. Induction of vascular superoxide production and remarkable endothelial dysfunction were also observed in them. Conclusions Hepatic ERK2 revealed the suppression of hepatic ER stress and HST in vivo , which resulted in protection from vascular oxidative stress and endothelial dysfunction. HST with hepatic ER stress can be a prominent risk of vascular complications by metabolic remodeling and oxidative stress in obese-related diseases.

scholarly journals Endoplasmic reticulum stress and oxidative stress drive endothelial dysfunction induced by high selenium

2020 ◽  
Author(s):  
Matshediso Zachariah ◽  
Hatem Maamoun ◽  
Larissa Milano ◽  
Margaret P. Rayman ◽  
Lisiane B. Meira ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endothelial Dysfunction ◽  
Endoplasmic Reticulum Stress ◽  
High Selenium ◽  
And Oxidative Stress

scholarly journals Urinary Biomarkers of Inflammation and Oxidative Stress Are Elevated in Obese Children and Correlate with a Marker of Endothelial Dysfunction

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Vaithinathan Selvaraju ◽  
Priscilla Ayine ◽  
Moni Fadamiro ◽  
Jeganathan Ramesh Babu ◽  
Michael Brown ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Childhood Obesity ◽  
Endothelial Dysfunction ◽  
Urine Samples ◽  
Low Grade ◽  
Oxidative Stress Markers ◽  
Obese Children ◽  
Stress Markers ◽  
Oxidative Markers ◽  
And Oxidative Stress

Obesity is a state of chronic low-level inflammation closely associated with oxidative stress. Childhood obesity is associated with endothelial dysfunction, inflammation, and oxidative stress markers individually. This study was aimed at determining the association between the biomarkers of inflammation, oxidative stress, and endothelial dysfunction in urine samples of healthy, overweight, and obese children. Eighty-eight elementary school children aged between 6 and 10 years participated in this study. Anthropometric measurements were measured using WHO recommendations. The biomarkers of low-grade inflammation such as C-reactive protein (CRP), interleukin-6 (IL-6), and α-1-acid glycoprotein (AGP); oxidative stress markers such as 8-isoprostane and 8-hydroxy-2′-deoxyguanosine (8-OHdG); and endothelin-1 (ET-1) were analyzed in urine samples. The area under the curve (AUC) by the receiver operating characteristics (ROC) was analyzed to identify the best urinary biomarker in childhood obesity. Linear regression and Pearson correlation were analyzed to determine the association between the parameters. The obese participants have significantly increased levels of CRP, AGP, IL-6, and 8-isoprostane compared to normal-weight participants. The overweight participants had significantly increased levels of ET-1 and 8-OHdG but not the obese group compared to the NW group. The AUC for urinary CRP (AUC: 0.847, 95% CI: 0.765-0.930; p<0.0001) and 8-isoprostane (AUC: 0.857, 95% CI: 0.783-0.932; p<0.0001) showed a greater area under ROC curves compared to other inflammatory and oxidative markers. The urinary CRP and 8-isoprostane significantly correlated with the obesity measures (body mass index, waist circumference, and waist-to- height ratio) and ET-1, inflammatory, and oxidative markers. The increased urinary inflammatory markers and 8-isoprostane can serve as a noninvasive benchmark for early detection of the risk of developing cardiovascular disease.

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