scholarly journals Vascular Inflammation and Dysfunction in Lupus-Prone Mice-IL-6 as Mediator of Disease Initiation

2021 ◽  
Vol 22 (5) ◽  
pp. 2291
Author(s):  
Paul Marczynski ◽  
Myriam Meineck ◽  
Ning Xia ◽  
Huige Li ◽  
Daniel Kraus ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lupus Erythematosus ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Intima Media Thickness ◽  
Leukocytic Infiltration ◽  
Increased Risk ◽  
Altered Immune Status ◽  
Inflammatory Autoimmune Disease ◽  
Excellent Tool

Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and patients are under an increased risk for cardiovascular (CV) events and mortality. The increased CV risk for patients with SLE seems to be caused by a premature and accelerated atherosclerosis, attributable to lupus-specific risk factors (i.e., increased systemic inflammation, altered immune status), apart from traditional CV risk factors. To date, there is no established experimental model to explore the pathogenesis of this increased CV risk in SLE patients. Methods: Here we investigated whether MRL-Faslpr mice, which develop an SLE-like phenotype, may serve as a model to study lupus-mediated vascular disease. Therefore, MRL-Faslpr, MRL-++, and previously generated Il6−/− MRL-Faslpr mice were used to evaluate vascular changes and possible mechanisms of vascular dysfunction and damage. Results: Contrary to MRL-++ control mice, lupus-prone MRL-Faslpr mice exhibited a pronounced vascular and perivascular leukocytic infiltration in various organs; expression of pro-inflammatory cytokines in the aorta and kidney was augmented; and intima-media thickness of the aorta was increased. IL-6 deficiency reversed these changes and restored aortic relaxation. Conclusion: Our findings demonstrate that the MRL-Faslpr mouse model is an excellent tool to investigate vascular damage in SLE mice. Moreover, IL-6 promotes vascular inflammation and damage and could potentially be a therapeutic target for the treatment of accelerated arteriosclerosis in SLE.

Abstract P293: Perivascular Adipose Tissue of the Descending Aorta is Associated with SLE and Vascular Calcification

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Kelly J Shields ◽  
Emma Barinas-Mitchell ◽  
Ping Tepper ◽  
Matthew R Gingo ◽  
Amy H Kao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Adipose Tissue ◽  
Regression Analysis ◽  
Lupus Erythematosus ◽  
Vascular Dysfunction ◽  
Linear Regression Analysis ◽  
Inflammatory Factors ◽  
Control Group ◽  
Perivascular Adipose Tissue ◽  
Increased Risk

Introduction: Women with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease (CVD). Traditional CVD and SLE related risk factors have been implicated, but do not fully account for this increased risk. Adipose produces pro-atherogenic components and visceral adipose is most strongly associated with vascular dysfunction and metabolic disorder. The proximity of perivascular adipose tissue (PVAT) to blood vessels may exacerbate vascular dysfunction and progression of CVD. Hypothesis: We hypothesized that SLE participants have increased PVAT surrounding the descending thoracic aorta with increased coronary artery calcification (CAC) and aortic calcification (AC) compared to healthy controls. PVAT is hypothesized to be positively associated with increased CAC and AC. Methods: Women participating in the: “Heart Effects on Atherosclerosis and Risk of Thrombosis in SLE” (HEARTS) study were clinically CVD-free, diagnosed with SLE for 2 years and age and race matched to healthy women, excluding those with diabetes (SLE, n=153; Control, n=158). The EBT scans were performed using an Imatron C-150 scanner. CAC/AC were quantified using Agatston scores and the PVAT was quantified using standard attenuations values for adipose tissue (−190 to −30 HU) on commercially available software. The total PVAT volume (tPVAT) was calculated by summing the areas and multiplying by the length of the participant’s aorta. Results and Conclusions: The SLE group had a greater tPVAT than the control group (p=0.0071) despite no differences in age, BMI, metabolic syndrome (MS), or waist or hip circumference. The SLE group was more likely to be hypertensive (p<0.0001) and had a larger waist to hip ratio (p=0.001 ) reflecting vascular dysfunction and a different adipose distribution. Total PVAT was associated with SLE (OR: 1.02, p=0.020) and the association remained significant after adjusting for CVD risk factors including BMI and MS (OR: 1.03, p=0.028). Based on linear regression analysis, the tPVAT in both SLE and controls was influenced by postmenopausal status, CRP, BMI, and MS, while history of smoking also influenced the control tPVAT. Unadjusted AC was associated with SLE by a factor of 2.3 (p=0.01), while there was no statistical difference between SLE and control for CAC. In logistic regression analysis, tPVAT was associated with AC (1.07,p<0.0001), which remained significant after adjusting for CVD and inflammatory factors including BMI and MS. The CAC (1.05,p<0.0001) association was attenuated with BMI and MS. In conclusion, tPVAT is greater in clinically CVD-free SLE versus control participants and is associated with AC independent of overall adiposity.

scholarly journals Risk factors for progression of carotid intima-media thickness in patients with systemic lupus erythematosus: protocol for an observational cohort study in China

BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e030721
Author(s):  
Haiyu Pang ◽  
Yicong Ye ◽  
Faming Ding ◽  
Mengtao Li ◽  
Xinglin Yang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Informed Consent ◽  
Lupus Erythematosus ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Systemic Lupus ◽  
Media Thickness ◽  
Artery Disease

IntroductionAccelerated atherosclerosis is a major complication of systemic lupus erythematosus (SLE), and it leads to increased cardiovascular morbidity and mortality in patients with SLE. This study aimed to investigate the natural progression of carotid intima-media thickness (CIMT), and to examine the risk factors for progression of CIMT and atherosclerotic plaques based on a Chinese SLE cohort.Methods and analysisParticipants were continuously enrolled as outpatients of the Department of Rheumatology in Peking Union Medical College Hospital (PUMCH) from October 2013 to December 2016. Inclusion criteria were as follows: (1) age ≥18 years, (2) fulfilment of clinical classification criteria of SLE and (3) provision of signed written informed consent. Patients with clinically overt coronary artery disease, a history of cardiovascular disease (previous stroke, heart failure, myocardial infarction, angina or symptomatic peripheral artery disease) and malignancy, and pregnant/lactating women were excluded. The primary outcome is progression of CIMT from baseline. A total of 440 patients with SLE will be enrolled. Participants will receive follow-up surveys ~5 years after their baseline visit. A standard structural survey form, including demographic data, medical history, clinical and laboratory assessments and CIMT measurement, is planned for data collection at baseline and follow-up. The risk prediction model for progression of CIMT will be created by using a mixed effect model.Ethics and disseminationThe study protocol was approved by the institutional review board of PUMCH (S-599). Informed consent was obtained from all participants according to the Declaration of Helsinki on Biomedical Research Involving Human Studies. All data will be managed confidentially according to guidelines and legislation. Dissemination will include publication of scientific papers and/or presentations of the study findings at international conferences.

scholarly journals Factors involved in the progress of preclinical atherosclerosis associated with systemic lupus erythematosus: a 2-year longitudinal study

2009 ◽  
Vol 69 (6) ◽  
pp. 1136-1139 ◽  
Author(s):  
I Rua-Figueroa ◽  
O Arencibia-Mireles ◽  
M Elvira ◽  
C Erausquin ◽  
S Ojeda ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Linear Regression ◽  
Multiple Linear Regression ◽  
Lupus Erythematosus ◽  
High Sensitivity ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Systemic Lupus ◽  
C5a Anaphylatoxin

ObjectivesTo assess the changes in carotid intima-media thickness (IMT) and the associated risks factors in patients with low severity systemic lupus erythematosus (SLE).MethodsCommon carotid IMT measurements were obtained by ultrasound from 101 patients with SLE at an interval of 2 years. Cardiovascular risk factors, disease activity, accumulated damage, severity (Katz index) and biochemical parameters (including high sensitivity C-reactive protein, interleukin 6, C3a, C4a, C5a and homocysteine) were also assessed. Multiple linear regression was used to assess the effect of these variables on the end IMT measurement (eIMT) adjusted to the baseline measurement (bIMT).ResultsThe cohort comprised 94.1% women, with a mean age at entry of 41.5 years and a mean disease duration of 12.1 years. An increase of 0.078 mm in IMT was detected over 2 years, from a mean bIMT of 0.37 mm to a mean eIMT of 0.44 mm (p<0.001). When adjusted for the bIMT, multiple linear regression identified bIMT, age at diagnosis, homocysteine, C3 and C5a as risk factors for IMT progression.ConclusionsIMT significantly increases over 2 years in patients with SLE. Age, baseline IMT, C3, C5a anaphylatoxin and homocysteine are all associated risk factors, supporting a role for complement and homocysteine in the early stages of premature SLE-associated atherosclerosis.

Osteoporosis in a murine model of postmenopausal lupus

Lupus ◽  
2019 ◽  
Vol 29 (1) ◽  
pp. 58-66
Author(s):  
J Nordqvist ◽  
M K Lagerquist ◽  
L Grahnemo ◽  
A Koskela ◽  
U Islander ◽  
...  
Keyword(s):  
Risk Factors ◽  
Computed Tomography ◽  
Systemic Lupus Erythematosus ◽  
Experimental Model ◽  
Lupus Erythematosus ◽  
Mineral Density ◽  
Systemic Lupus ◽  
New Therapies ◽  
Increased Risk ◽  
Bone Remodeling Markers

Background/objective Postmenopausal women with systemic lupus erythematosus have an increased risk of osteoporosis and associated fractures. Their increased osteoporosis risk is probably caused by a high level of inflammation, use of glucocorticoids, impaired kidney function, and early menopause as these are known risk factors for osteoporosis. Due to these risk factors and the lack of safe and effective treatments, new therapies for the treatment of osteoporosis in this group of patients are needed. Ovariectomized MRL/ lpr mice constitute a well-established model for studies of postmenopausal systemic lupus erythematosus; however, it is not clear to what extent this experimental model is associated with the development of osteoporosis. Thus, the aim of this study was to characterize the skeleton of ovariectomized MRL/ lpr mice to determine the suitability of this model in studies of prospective new therapies for osteoporosis in postmenopausal systemic lupus erythematosus patients. Methods Skeletal parameters were measured in MRL/ lpr mice and MRL/++ control mice, using peripheral quantitative computed tomography, high-resolution micro-computed tomography and biomechanical analyses. mRNA expression of bone-remodeling markers was measured by quantitative polymerase chain reaction and serological markers of lupus disease were evaluated using ELISA. Results Total bone mineral density was reduced in MRL/ lpr mice compared with MRL/++ mice and MRL/ lpr mice had reduced cortical and trabecular bone thickness compared with MRL/++ mice. In line with the low bone mass of MRL/ lpr mice, gene expression analysis of cortical bone from these mice indicated an increased osteoclast activity as well as a decreased osteoblastogenesis and osteoblast activity, compared with MRL/++ mice. Conclusion Ovariectomized MRL/ lpr mice constitute a valuable experimental model for studies of osteoporosis development in postmenopausal systemic lupus erythematosus and this model is thus suitable for future studies of osteoporosis treatment in systemic lupus erythematosus.

Cardiovascular Disease in Systemic Lupus Erythematosus: Recent Data on Epidemiology, Risk Factors and Prevention

2020 ◽  
Vol 18 (6) ◽  
pp. 549-565 ◽  
Author(s):  
Myrto Kostopoulou ◽  
Dionysis Nikolopoulos ◽  
Ioannis Parodis ◽  
George Bertsias
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Statin Treatment ◽  
Type I Interferons ◽  
Type I ◽  
Lifestyle Modifications ◽  
Systemic Lupus ◽  
Increased Risk ◽  
Atherogenic Dyslipidaemia

Systemic Lupus Erythematosus (SLE) is associated with increased risk for accelerated atherosclerosis and cardiovascular (CV) events including coronary heart disease, cerebrovascular and peripheral artery disease. CV events occur both early and late during the disease course, with younger patients being at much higher risk than age-matched counterparts. The risk cannot be fully accounted for by the increased prevalence of traditional atherosclerotic factors and may be due to pathophysiologic intermediates such as type I interferons and other inflammatory cytokines, oxidative stress, activated granulocytes and production of extracellular chromatin traps, antiphospholipid and other autoantibodies causing dysfunction of lipoproteins, altogether resulting in endothelial injury and pro-atherogenic dyslipidaemia. These mechanisms may be further aggravated by chronic intake of prednisone (even at doses <7.5 mg/day), whereas immunomodulatory drugs, especially hydroxychloroquine, may exert antiatherogenic properties. To date, there is a paucity of randomized studies regarding the effectiveness of preventative strategies and pharmacological interventions specifically in patients with SLE. Nevertheless, both the European League Against Rheumatism recommendations and extrapolated evidence from the general population emphasize that SLE patients should undergo regular monitoring for atherosclerotic risk factors and calculation of the 10-year CV risk. Risk stratification should include diseaserelated factors and accordingly, general (lifestyle modifications/smoking cessation, antihypertensive and statin treatment, low-dose aspirin in selected cases) and SLE-specific (control of disease activity, minimization of glucocorticoids, use of hydroxychloroquine) preventive measures be applied as appropriate. Further studies will be required regarding the use of non-invasive tools and biomarkers for CV assessment and of risk-lowering strategies tailored to SLE.

ROLE OF INFLAMMATION AND PLATELETS ACTIVATION IN ATHEROSCLERISIS PROGRESSION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

2018 ◽  
Author(s):  
А.В. Аршинов ◽  
Н.Ю. Левшин ◽  
И.Г. Маслова ◽  
А.Н. Лужинский
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Intima Media Thickness ◽  
Control Group ◽  
Systemic Lupus ◽  
Reactive Protein ◽  
Traditional Risk Factors ◽  
Atherosclerosis Development ◽  
Aggregation Activity

Цель исследования: выявить взаимосвязь между дислипидемией, активностью воспаления и функцией тромбоцитов в развитии атеросклероза у пациентов с системной красной волчанкой (СКВ), а также оценить сходство и различия механизмов атерогенеза у больных СКВ и ишемической болезнью сердца. Материалы и методы. Обследовано 102 женщины, из них — 50 больных СКВ, 31 — с инфарктом миокарда (ИМ); контрольную группу составили здоровые женщины (n = 21). Определяли показатели липидного спектра, содержание антител к окисленным липопротеинам низкой плотности (АТ-оксЛПНП), высокочувствительного С-реактивного белка (вчСРБ), интерлейкина 6 (ИЛ-6), тромбоцитарного фактора 4 (ТФ4), агрегационную функцию тромбоцитов и толщину комплекса интима-медиа (ТКИМ) общих сонных артерий. Результаты. У больных СКВ и у пациентов с ИМ выявлено значительное увеличение ТКИМ сонной артерии и выраженная активация воспаления: повышение содержания вчСРБ, ИЛ-6 и увеличение СОЭ. За исключением значений ИЛ-6, лабораторные показатели воспаления у больных СКВ и с ИМ достоверно не различались. Также у пациентов с СКВ и ИМ установлена значительная активация тромбоцитов (достоверный рост содержания ТФ4). Несмотря на наличие дислипидемии в обеих группах, у больных СКВ данные изменения были выражены более отчётливо и сопровождались повышением уровня АТ-оксЛПНП. Заключение. Кроме традиционных факторов риска развития сердечно-сосудистых заболеваний, ассоциация между СКВ и атеросклерозом может быть объяснена дополнительными факторами риска — воспалением и аутоиммунными процессами. Aim: to reveal a relationship between dyslipidemia, infl ammatory activity and platelets reactivity in atherosclerosis development in patients with systemic lupus erythematosus (SLE) and also to assess the similarity and diff erences of atherogenesis mechanisms in patients with SLE and ischemic heart disease. Materials and methods. The study included 102 women: 50 patients with SLE, 31 — with myocardial infarction (MI); control group included 21 healthy women. We measured parameters of lipid spectrum, levels of antibodies against oxidized low density lipoproteins (oxLDL), high-sensitive C-reactive protein (hsCRP), interleukin 6 (IL-6), platelets factor 4 (PF4), platelets aggregation activity and complex intima-media thickness (TCIM) of carotid arteries. Results. Patient with SLE and MI had markedly increased TCIM. Increased infl ammation activity was the second sign of two groups of patients, including increased hsCRP, IL-6, erythrocyte sedimentation test. Laboratory signs of infl ammation did not markedly diff er in two groups except IL-6. Our study also revealed considerable platelets activation in patients with SLE and MI (signifi cant growth of PF4 content). Despite dyslipidemia, all indicated changes were more clearly expressed in patients with SLE; they were accompanied by increased level of antibodies against oxLDL. Conclusion. Except traditional risk factors for cardiovascular diseases development the association between SLE and atherosclerosis. can be explained by additional risk factors — infl ammation and autoimmune processes.

scholarly journals The Epidemiological Boehringer Ingelheim Employee Study—Part I: Impact of Overweight and Obesity on Cardiometabolic Risk

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Kerstin Kempf ◽  
Stephan Martin ◽  
Carmen Döhring ◽  
Klaus Dugi ◽  
Carolin Wolfram von Wolmar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Large Scale ◽  
Cardiometabolic Risk ◽  
Intima Media Thickness ◽  
Roc Curves ◽  
Overweight And Obesity ◽  
Cardiometabolic Risk Factors ◽  
Cross Sectional ◽  
The Metabolic Syndrome ◽  
Increased Risk

Objective.Obesity-dependent diseases cause economic burden to companies. Large-scale data for working populations are lacking. Prevalence of overweight and obesity in the Boehringer Ingelheim (BI) Employee cohort and the relationship between body mass index (BMI) and cardiometabolic risk factors and diseases were estimated.Design and Methods.Employees (≥38 years, employed in Ingelheim ≥2 years;n=3151) of BI Pharma GmbH & Co. KG were invited by the medical corporate department to participate in intensive health checkups. Cross-sectional analysis of baseline data collected through 2006–2011 was performed.Results.90% of eligible subjects participated (n=2849). Prevalences of overweight and obesity were 40% and 18% and significantly higher in men and participants ≥50 years. Cardiometabolic risk factor levels and prevalences of cardiometabolic diseases significantly increased with BMI and were higher in overweight and obese participants. Cut-points for increased risk estimated from ROC curves were≈25 kg/m2for hypertension, hypercholesterolemia, arteriosclerosis, and hypertriglyceridemia and 26.7–28.0 kg/m2for the metabolic syndrome, insulin resistance, hyperinsulinemia, increased intima media thickness, and type 2 diabetes.Conclusion.This is the first large-scale occupational health care cohort from a single company. Cardiometabolic risk factors and diseases accumulate with increasing BMI. Occupational weight reduction programs seem to be reasonable strategies.

scholarly journals Imaging Assessment of Cardiovascular Disease in Systemic Lupus Erythematosus

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Sara C. Croca ◽  
Anisur Rahman
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Lupus Erythematosus ◽  
Current Status ◽  
Systemic Lupus ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk ◽  
Cardiovascular Assessment

Systemic lupus erythematosus is a multisystem, autoimmune disease known to be one of the strongest risk factors for atherosclerosis. Patients with SLE have an excess cardiovascular risk compared with the general population, leading to increased cardiovascular morbidity and mortality. Although the precise explanation for this is yet to be established, it seems to be associated with the presence of an accelerated atherosclerotic process, arising from the combination of traditional and lupus-specific risk factors. Moreover, cardiovascular-disease associated mortality in patients with SLE has not improved over time. One of the main reasons for this is the poor performance of standard risk stratification tools on assessing the cardiovascular risk of patients with SLE. Therefore, establishing alternative ways to identify patients at increased risk efficiently is essential. With recent developments in several imaging techniques, the ultimate goal of cardiovascular assessment will shift from assessing symptomatic patients to diagnosing early cardiovascular disease in asymptomatic patients which will hopefully help us to prevent its progression. This review will focus on the current status of the imaging tools available to assess cardiac and vascular function in patients with SLE.

Cardiovascular disease in systemic lupus erythematosus

2021 ◽  
Vol 2 (3) ◽  
pp. 157-172
Author(s):  
Maureen McMahon ◽  
Richard Seto ◽  
Brian J. Skaggs
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Disease ◽  
Lupus Erythematosus ◽  
Cardiovascular Events ◽  
Subclinical Atherosclerosis ◽  
Cardiac Risk ◽  
Systemic Lupus ◽  
Cardiac Risk Factors ◽  
Increased Risk

Abstract There is a well-known increased risk for cardiovascular disease that contributes to morbidity and mortality in systemic lupus erythematosus (SLE). Major adverse cardiovascular events and subclinical atherosclerosis are both increased in this patient population. While traditional cardiac risk factors do contribute to the increased risk that is seen, lupus disease-related factors, medications, and genetic factors also impact the overall risk. SLE-specific inflammation, including oxidized lipids, cytokines, and altered immune cell subtypes all are likely to play a role in the pathogenesis of atherosclerotic plaques. Research is ongoing to identify biomarkers that can help clinicians to predict which SLE patients are at the greatest risk for cardiovascular disease (CVD). While SLE-specific treatment regimens for the prevention of cardiovascular events have not been identified, current strategies include minimization of traditional cardiac risk factors and lowering of overall lupus disease activity.

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