Cardiovascular Disease In Systemic Lupus Erythematosus Research Articles

Cardiovascular changes in the NZB/W F1 mouse model of lupus nephritis.

Patients with systemic lupus erythematosus (SLE), an autoimmune disease, have a higher risk of cardiovascular (CV) disease and death. In addition, up to 40%-50% of SLE patients develop lupus nephritis (LN) and chronic kidney disease, which is an additional CV risk factor. Thus, the individual contributions of LN and other SLE-specific factors to CV events are unclear. In this study, we investigated the effect of LN on the development of CV changes using the female NZBxNZW F1 (NZB/W) mouse model of lupus-like disease, with female NZW mice as controls. Standard serologic, morphologic, immunohistologic, and molecular analyses were performed. In a separate group of NZB/W mice, systolic blood pressure (BP) was measured during the course of the disease using tail plethysmography. Our data show marked CV changes in NZB/W mice, i.e., increased heart weight, hypertrophy of the left ventricle (LV) and septum, and increased wall thickness of the intramyocardial arteries and the aorta, which correlated with the progression of renal damage, but not with the age of the mice. In addition, systolic BP was increased in NZB/W mice only when kidney damage progressed and proteinuria was present. Pathway analysis based on gene expression data revealed a significant upregulation of the response to interferon beta in NZB/W mice with moderate kidney injury compared with NZB mice. Furthermore, IFI202b and IL-6 mRNA expression is correlated with CV changes. Multiple linear regression analysis demonstrated serum urea as a surrogate marker of kidney function and IFI202b expression as an independent predictor for LV wall thickness. In addition, deposition of complement factors CFD and C3c in hearts from NZB/W mice was seen, which correlated with the severity of kidney disease. Thus, we postulate that the pathogenesis of CV disease in SLE is affected by renal impairment, i.e., LN, but it can also be partly influenced by lupus-specific cardiac expression of pro-inflammatory factors and complement deposition.

Coronary Artery Disease in Systemic Lupus Erythematosus: What Do the Facts Say?

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect any organ with a predisposition for women of reproductive age.It is related to a higher risk of cardiovascular events, increasing it up to 50 times in young people, and 30% of deaths are attributed to coronary artery disease.The risk of developing cardiovascular disease in SLE is related not only to traditional cardiovascular risksfactors such as advanced age, hypertension, dyslipidemia, and diabetes but also to disease-specific factors, such as degree of activity, autoantibodies, organ damage, and treatment.Accelerated atherosclerosis is one of the main contributors to pathogenesis.Manifestations range from angina to acute myocardial infarction and sudden death.Markers have been studied for the detection of subclinical disease and stratification of these patients, as well as different treatment options to improve the cardiovascular prognosis of the disease.

1026 MYOCARDIAL INFARCTION AND STROKE IN A YOUNG PATIENT AFFECTED BY LES: KEY ROLE OF AN INTEGRATED IMAGING APPROACH

Abstract A male patient, 33 years old, smoker, with a 20-year history of SLE, consulted the ER for right hand fatigue. He didn't assume his medications constantly. Computed Tomography showed a fronto-parieto-occipital cerebral infarction, and the angio-CT showed a plaque in left internal carotid artery. The patient was admitted to the Stroke Unit for minor ischemic stroke. The ECG showed pathological Q waves in the anterior leads from V1 to V4 revealing a likely previous silent myocardial infarction. The echocardiogram demonstrated moderate left ventricular dysfunction with 40% EF and segmental wall motion abnormalities, namely ipoakinesia of anterior wall and apex. This findings were confirmed by cardiac MRI highliting subendocardial LGE in these areas suggesting an ischemic genesis. Due to the hemorrhagic risk related to recent cerebral ischemic event, coronary angiography was postponed a month later. The coronary angiography revealed a significant stenosis of the proximal left anterior descending artery (iFR < 0.65). Qualitative assessment of the lesion with IVUS showed a “mixed” plaque. The lesion was treated with PCI and the implant of two overlapped DES and the patient underwent dual antiplatelet therapy. Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with heterogeneous presentation, characterised by alternating periods of flares and remission, and irreversible organ damage. The skin, joints, heart, kidneys, central nervous system and haematologic system are some of the most affected organs. Although recent data suggest that mortality decreased in patients with SLE over the last 30 years, mortality due to cardiovascular disease (CVD), usually defined as a combination of coronary, cerebrovascular and/or peripheral arterial disease, has remained high. Stroke and myocardial infarction (MI) are major CVD events that are potentially life-threatening. Lupus specific cardiovascular risk factors are believed to contribute to the high risk for MI, such as renal involvement, that has been associated with increased subclinical atherosclerosis and ischaemic heart disease, and antiphospholipid syndrome (APS), defined by venous, arterial or small vessel thrombosis and/or obstetric complications together with persistent positivity for antiphospholipid antibodies (aPL). Though several risk factors have been suggested, the exact mechanisms behind the high MI incidence in SLE remain essentially unknown. MIs in SLE are in most cases associated with coronary atherosclerosis. Subclinical atherosclerosis has been reported in many case–control studies, but a direct causal relationship between coronary artery disease (CAD) and MI in SLE has not yet been well documented. The pathogenesis of cardiovascular diseases in SLE is not fully understood. The inflammatory nature of SLE is believed to be an important factor in accelerating atherosclerosis. Systemic inflammation may lead to an abnormal lipid profile with elevated triglycerides, total cholesterol, and low-density lipoprotein cholesterol and dysfunctional high-density lipoprotein cholesterol. Additionally, promotes endothelial dysfunction and vascular injury. Our case showed the key role of an integrated imaging approach with echocardiography and cardiac MRI to confirm diagnosis of past myocardial infarction in a very young man affected by LES. IVUS played a great role to characterize the nature of the lesion, confirming the association between coronary atherosclerosis and MIs in SLE.

Immune mechanisms associated with cardiovascular disease in systemic lupus erythematosus: A path to potential biomarkers.

Systemic lupus erythematosus (SLE) patients display an increased risk of cardiovascular disease (CVD). With the improved clinical management of other classical severe manifestation of the disease, CVD is becoming one of the most relevant complications of SLE, and it is an important factor causing morbidity and mortality. Several immune constituents have been shown to be involved in the pathogenesis of atherosclerosis and endothelial damage in SLE patients, including specific circulating cell populations, autoantibodies, and inflammatory mediators. In this review, we summarize the presentation of CVD in SLE and the role of the autoimmune responses present in SLE patients in the induction of atherogenesis, endothelial impairment and cardiac disease. Additionally, we discuss the utility of these immune mediators as early CVD biomarkers and targets for clinical intervention in SLE patients.

Systemic lupus erythematosus and cardiovascular disease.

The prognosis in systemic lupus erythematosus (SLE) has improved due to better treatment and care, but cardiovascular disease (CVD) still remains an important clinical problem, since the risk of CVD in SLE is much higher than among controls. Atherosclerosis is the main cause of CVD in the general population, and in SLE, increased atherosclerosis, especially the prevalence of atherosclerotic plaques, has been demonstrated. Atherosclerosis is an inflammatory condition, where immunity plays an important role. Interestingly, oxidized low-density lipoprotein, defective clearance of dead cells, and inflammation, with a pro-inflammatory T-cell profile are characteristics of both atherosclerosis and SLE. In addition to atherosclerosis as an underlying cause of CVD in SLE, there are also other non-mutually exclusive mechanisms, and the most important of these are antiphospholipid antibodies (aPL) leading to the antiphospholipid antibody syndrome with both arterial and venous thrombosis. aPL can cause direct pro-inflammatory and prothrombotic effects on endothelial and other cells and also interfere with the coagulation, for example, by inhibiting annexin A5 from its antithrombotic and protective effects. Antibodies against phosphorylcholine (anti-PC) and other small lipid-related epitopes, sometimes called natural antibodies, are negatively associated with CVD and atherosclerosis in SLE. Taken together, a combination of traditional risk factors such as hypertension and dyslipidemia, and nontraditional ones, especially aPL, inflammation, and low anti-PC are implicated in the increased risk of CVD in SLE. Close monitoring of both traditional risk factors and nontraditional ones, including treatment of disease manifestations, not lest renal disease in SLE, is warranted.

Endothelial function and endothelial progenitor cells in systemic lupus erythematosus

The observations that traditional cardiovascular disease (CVD) risk factors fail to fully account for the excessive cardiovascular mortality in patients with systemic lupus erythematosus (SLE) compared with the general population have prompted in-depth investigations of non-traditional, SLE-related risk factors that contribute to cardiovascular complications in patients with SLE. Of the various perturbations of vascular physiology, endothelial dysfunction, which is believed to occur in the earliest step of atherosclerosis, has been extensively investigated for its contribution to CVD risk in SLE. Endothelial progenitor cells (EPCs), which play a crucial part in vascular repair, neovascularization and maintenance of endothelial function, are quantitatively and functionally reduced in patients with SLE. Yet, the lack of a unified definition of EPCs, standardization of the quantity and functional assessment of EPCs as well as endothelial function measurement pose challenges to the translation of endothelial function measurements and EPC levels into prognostic markers for CVD in patients with SLE. This Review discusses factors that contribute to CVD in SLE, with particular focus on how endothelial function and EPCs are evaluated currently, and how EPCs are quantitatively and functionally altered in patients with SLE. Potential strategies for the use of endothelial function measurements and EPC quantification as prognostic markers of CVD in patients with SLE, and the limitations of their prognostication potential, are also discussed.

Cardiovascular disease risk and pathogenesis in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) often features extensive cardiovascular (CV) comorbidity and patients with SLE are at significantly increased risk of CV event occurrence and CV-related mortality. While the specific mechanisms leading to this increased cardiovascular disease (CVD) risk remain to be fully characterized, this heightened risk cannot be fully explained by traditional CV risk factors and is likely driven by immunologic and inflammatory features of SLE. Widespread innate and adaptive immune dysregulation characterize SLE, and factors including excessive type I interferon burden, inappropriate formation and ineffective clearance of neutrophil extracellular traps, and autoantibody formation have been linked to clinical and metabolic features impacting CV risk in SLE and may represent pathogenic drivers of SLE-related CVD. Indeed, functional and phenotypic aberrations in almost every immune cell type are present in SLE and may impact CVD progression. As understanding of the contribution of SLE-specific factors to CVD in SLE improves, improved screening and monitoring of CV risk alongside development of therapeutic treatments aimed at prevention of CVD in SLE patients are required and remain the focus of several ongoing studies and lines of inquiry.

Systemic Lupus Erythematosus and Cardiovascular Disease.

Systemic lupus erythematosus (SLE) is a condition in which autoimmune inflammation affects nearly every organ in the human body; it is characterized by a relapsing-remitting pattern. Systemic inflammation and tissue damage can arise from autoantibodies, the creation of immune complexes, and the deposition of autoantibodies, all defined as autoimmune diseases. Women of reproductive age are at a high risk of developing lupus, a chronic systemic condition. Among women between the ages of 15 and 44 years, the female-to-male ratio for the occurrence of lupus is as high as 13:1, while it is only 2:1 in children and in the elderly. In addition to accelerated atherosclerosis, SLE is associated with an increased risk of cardiovascular (CV) events such as coronary artery disease (CAD), peripheral artery disease (PAD), and cerebrovascular accident (CVA). Several SLE-specific processes, including impaired immunological regulation, impaired endothelial cell (EC) function, impaired vascular repair, hyperleptinemia, and traditional risk factors, contribute to early atherosclerosis in the disease. CAD can occur at any stage of the disease's progression, with younger individuals being much more at risk than their age-matched counterparts. This review article aims to provide a unique insight into the relationship between SLE and cardiovascular disease (CVD) by discussing the pathophysiological role of CVD in SLE, outlining screening criteria, and highlighting the treatment options for CVD in connection with SLE.

Metabolic syndrome at baseline was not predictive to new-onset cardiovascular diseases in patients with systemic lupus erythematosus: A prospective observational registry

Objective: It has been established that metabolic syndrome is prevalent in patients with systemic lupus erythematosus (SLE). The objective of this study was to investigate the effect of metabolic syndrome at baseline on new-onset cardiovascular disease (CVD) in patients with SLE. Methods: The demographic and lupus-related clinical variables of 229 patients with SLE were collected from the Korean Lupus Network (KORNET) registry. Metabolic syndrome was defined by the modified National Cholesterol Education Program’s Adult Treatment Panel III (NCEP ATP III) criteria. Binary logistic regression analysis was applied to identify clinical variables including metabolic syndrome related to pre-existing CVD at the time of enrollment or new-onset CVD during 3 years of follow-up. Results: Patients with pre-existing CVD at baseline had higher rates of metabolic syndrome than those without CVD in SLE ( p = .022), whereas there was no difference in the frequency of metabolic syndrome between patients with and without new-onset CVD. Logistic regression analysis revealed that metabolic syndrome and the number of its components were associated with pre-existing CVD, together with body mass index and hypertriglyceridemia. Metabolic syndrome at baseline and its components were not related with increased risk of new-onset CVD. On the contrary, anti-dsDNA antibody titer, anti-ds DNA positivity, and lower diastolic blood pressure increased the risk of new-onset CVD. Conclusion: This study demonstrated that metabolic syndrome at baseline was not predictive to new-onset CVD at 3 years of follow-up, although it was associated with pre-existing CVD in SLE.

Impaired Microcirculation and Vascular Hemodynamics in Relation to Macrocirculation in Patients With Systemic Lupus Erythematosus.

Introduction: Systemic lupus erythematosus (SLE) is associated with premature cardiovascular disease (CVD) and mortality, unexplained by traditional risk factors. Impairment of microcirculation and vascular hemodynamics may represent early signs of vascular affection. We hypothesized that studies of microcirculation and pulse waves may provide additional information, compared to ultrasound (US) alone, for the detection of early vascular disease in SLE.Methods: Sixty well-characterized SLE-patients (52 women, eight men; mean age 43.21 ± 1.3 years) characterized by lupus nephritis (LN; n = 20), antiphospholipid syndrome (APS; n = 20) or skin and joint involvement (n = 20) and 60 healthy controls were included. Microcirculatory peak oxygen saturation (OxyP) was evaluated using a novel combined laser Doppler flowmetry/diffuse reflectance spectroscopy method. Pulse waves were recorded in the radial artery by the aid of applanation tonometry in order to calculate central augmentation index (AIx75). Intima-media thickness (IMT) and plaque occurrence were evaluated using high frequency US, in carotid and central arteries.Results: Lower OxyP (84 ± 8 vs. 87 ± 5 %, p = 0.01) and higher AIx75 (17.3 ± 13.9 vs. 10.0 ± 14.2 %, p = 0.005) were seen in the SLE cohort. OxyP was inversely correlated with IMT in internal carotid artery (ICA), (R = −0.32, p = 0.01). AIx75 correlated with IMT in common carotid artery (CCA), (R = 0.36, p = 0.005), common femoral artery (CFA), (R = 0.43, p = 0.001), and ICA (R = 0.27, p = 0.04). AIx75 correlated negatively with OxyP (R = −0.29, p = 0.02). SLE-patients with plaque had lower OxyP values (80 ± 8 vs. 85 ± 7 %, p < 0.001) and higher AIx75 (23.0 ± 11.6 vs. 15.5 ± 14.2 %, p < 0.001) compared to those without plaque.Conclusion: Impaired microcirculation and vessel hemodynamics were observed in SLE. These methods correlated with IMT and plaque occurrence. The importance of early macro- and micro-circulatory vascular affection for increased risk of CVD in SLE will be followed-up in future studies.

Understanding Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Toward Better Treatment and Prevention.

Systemic lupus erythematosus (SLE) carries a significant risk of cardiovascular disease (CVD). The prevalence of premature CVD is especially noteworthy because it occurs in premenopausal women with SLE who would otherwise have very low rates of CVD. While traditional risk factors likely play a role in development of CVD in the setting of SLE, they do not fully explain the excess risk. The pathogenesis of CVD in SLE is not fully understood, but the inflammatory nature of SLE is believed to be a key factor in accelerating atherosclerosis. Systemic inflammation may lead to an abnormal lipid profile with elevated triglycerides, total cholesterol, and low-density lipoprotein cholesterol and dysfunctional high-density lipoprotein cholesterol. Additionally, the inflammatory milieu of SLE plasma promotes endothelial dysfunction and vascular injury, early steps in the progression of atherosclerotic CVD. Despite the overall headway that has been achieved in treating lupus, innovative therapeutics specifically targeting the progression of atherosclerosis within the lupus population are currently lacking. However, there have been advancements in the development of promising modalities for diagnosis of subclinical atherosclerosis and detection of high CVD risk patients. Due to the significant impact of CVD on morbidity and mortality, research addressing prevention and treatment of CVD in SLE needs to be prioritized. This review explores the intricate interplay of SLE-specific properties that contribute to atherosclerosis and CVD within this population, as well as screening methods and possible therapies.

Combined Brain/Heart Magnetic Resonance Imaging in Systemic Lupus Erythematosus.

Cardiovascular Disease (CVD) in Systemic Lupus Erythematosus (SLE) and Neuropsychiatric SLE (NPSLE) has an estimated prevalence of 50% and 40%, respectively and both constitute major causes of death among SLE patients. In this review, a combined brain/heart Magnetic Resonance Imaging (MRI) for SLE risk stratification has been proposed.The pathophysiologic background of NPSLE includes microangiopathy, macroscopic infarcts and accelerated atherosclerosis. Classic brain MRI findings demonstrate lesions suggestive of NPSLE in 50% of the NPSLE cases, while advanced MRI indices can detect pre-clinical lesions in the majority of them, but their clinical impact still remains unknown. Cardiac involvement in SLE includes myo-pericarditis, valvular disease/endocarditis, Heart Failure (HF), coronary macro-micro-vascular disease, vasculitis and pulmonary hypertension. Classic and advanced Cardiovascular Magnetic Resonance (CMR) indices allow function and tissue characterization for early diagnosis and treatment follow-up of CVD in SLE.Although currently, there are no clinical data supporting the combined use of brain/heart MRI in asymptomatic SLE, it may have a place in cases with clinical suspicion of brain/heart involvement, especially in patients at high risk for CVD/stroke such as SLE with antiphospholipid syndrome (SLE/APS), in whom concurrent cardiac and brain lesions have been identified. Furthermore, it may be of value in SLE with multi-organ involvement, NPSLE with concurrent cardiac involvement, and recent onset of arrhythmia and/or heart failure.

Protective Effects of Probiotic Consumption in Cardiovascular Disease in Systemic Lupus Erythematosus.

The prevalence of renal and cardiovascular disease (CVD) in patients with systemic lupus erythematosus (SLE) is higher than in general populations. Recently, a causal role of gut microbiota on the development of immune responses in SLE has been described. Probiotic consumption changes the composition of gut microbiota, preventing SLE progression. The aim of this review is to explore the role of the gut microbiota in the development of renal and cardiovascular disease in SLE and how probiotics could be a therapeutic option. Despite strong evidence on the beneficial effects of probiotics in the development of autoimmunity and nephritis in SLE, only a few studies described the protective effects of Lactobacillus in important risk factors for CVD, such as endothelial dysfunction and hypertension in mice. The preventive effects of probiotics in renal and CVD in humans have not been established yet.

Innate Immune Dysregulation in the Development of Cardiovascular Disease in Lupus.

The systemic inflammatory nature of systemic lupus erythematosus (SLE) is patent not only in the diverse clinical manifestations of the disease but also in the increased risk of premature cardiovascular diseases (CVD). In this review, we discuss the latest findings on the key factors of the innate immune system known to play critical roles in the pathogenesis of accelerated CVD in patients with SLE and discuss the potential that immunometabolism may play a key role in this respect. Recent studies exploring the association between SLE and premature CVD clearly showed that alterations of specific immune functions play a pivotal role in the increased cardiovascular morbidity and mortality in the SLE patients. Novel molecular factors such as type I interferons (IFN), dysregulated neutrophil function, and changes to cellular metabolism and metabolites are emerging as important regulators of systemic immune dysfunction and as strong risk factors for premature CVD in SLE. Although corticosteroids and cytotoxic agents can be used to effectively manage and control various lupus-related complications, to date, no drug has been proven to prevent the development of premature atherosclerosis in SLE. However, as new mechanisms underlying this complication of SLE are uncovered, such as the role of metabolism and neutrophil-driven inflammation, new avenues for therapeutic intervention are being discovered.

Predictive values of dyslipidemia and B-type natriuretic peptide levels in juvenile systemic lupus erythematosus: A two center-experience.

B-type natriuretic peptide (BNP) is a biomarker that helps in determining the diagnosis and prognosis of heart failure (HF). There is an increased risk for cardiovascular disease (CVD) in systemic lupus erythematosus (SLE) with high disease activity, demonstrated by the higher frequency of dyslipidemia and higher BNP concentrations than in healthy controls. The aim of the work was to evaluate the association between the levels of lipids and BNP in pediatric patients with SLE with HF. We classified our subjects into three groups as follows: Group 1 (active SLE group): included 38 patients who subgrouped into 16 with HF and 22 without HF; Group 2 (inactive SLE group): included 38 patients, and Group 3 (control group): included 38 apparently healthy children. All children were subjected to complete history taking, clinical examination, SLE disease activity index scoring and investigations included complete blood count, erythrocyte sedimentation rate, 24-h urinary protein, anti-double strand deoxy-ribonucleic acid and anti-nuclear antibody, lipid profile, serum albumin, protein, and BNP. There was a significantly elevated lipid level and decreased high-density lipoproteins in lupus patients than in healthy controls. The dyslipidemia was more prevalent in active SLE. There were significantly elevated BNP levels in lupus patients than in healthy controls. In this study, we found that BNP was a biomarker in determining the diagnosis and prognosis of HF. This study revealed that BNP levels were increased in SLE patients without cardiac symptoms as compared to healthy controls; furthermore, the BNP levels were higher in active SLE patients with HF. The data indicated that there is a high risk for CVD in SLE with high disease activity, as demonstrated by the higher frequency of dyslipidemia and higher BNP concentrations than in healthy controls.

Endothelial cell injury is involved in atherosclerosis and lupus symptoms in gld.apoE- / - mice.

Cardiovascular complications related to atherosclerosis are major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). However, the underlying mechanisms are not fully understood. Endothelial dysfunction has been identified as having involvement in pathogenesis of cardiovascular diseases and SLE. This study aims to evaluate endothelial cell injury in mice with the combination of lupus and atherosclerosis. The mouse model of accelerated atherosclerosis in lupus (gld.apoE- / - mouse) was generated from apolipoprotein E-deficient (apoE- / - ) and Faslgld C57BL/6 mice. The lupus-like autoimmunity and atherosclerotic lesions were evaluated. The endothelial cell injury was determined. The results showed that the double-mutant gld.apoE- / - mice were generated. Spleens from 5-month-old gld.apoE- / - mice were significantly enlarged compared with wild-type mice (WT mice). The gld.apoE- / - mice produced high levels of total immunoglobulin G (IgG) and IgM and showed marked increase of IgG and C3 deposits in the glomeruli. The gld.apoE- / - mice displayed a pattern of glomerulonephritis typically found in SLE. The gld.apoE- / - mice have high levels of serum creatinine. The total cholesterol, low-density lipoprotein cholesterol and triglycerides were significantly increased, while high-density lipoprotein cholesterol decreased in the double-mutant mice. The circulating endothelial progenitor cells were significantly decreased. The serum levels of thrombomodulin and vascular cell adhesion molecule-1 were significantly elevated in gld.apoE- / - mice. The gld.apoE- / - mice simultaneously exhibited SLE and atherosclerosis characteristics. Our findings indicated that endothelial cell injury might be a biomarker for evaluating risks of cardiovascular disease in SLE and targeting endothelial cell dysfunction might prevent and treat atherosclerosis in SLE.

Novel gene variants associated with cardiovascular disease in systemic lupus erythematosus and rheumatoid arthritis

ObjectivesPatients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) have increased risk of cardiovascular disease (CVD). We investigated whether single nucleotide polymorphisms (SNPs) at autoimmunity risk loci were associated...

Vitamin D and juvenile systemic lupus erythematosus: Lights, shadows and still unresolved issues.

Systemic lupus erythematosus (SLE) and juvenile SLE (jSLE) are autoimmune disorders naturally associated with several genetic, environmental, hormonal, and immunological contributing factors. It has been assumed that vitamin D deficiency may have a role in the immune activation of patients with SLE and play an active part in many comorbidities and even complications. A host of clinical studies suggested that vitamin D exerts inhibitory effects on many immunological abnormalities associated with SLE, also in children and adolescents, while different reports have hypothesized that vitamin D may be associated with accelerated cardiovascular disease in SLE. This review updates and summarizes the information related to the immunoregulatory effects of vitamin D and its importance in jSLE, discusses the innumerable correlations between vitamin D and disease activity, including clinical expression and gene polymorphisms of vitamin D receptor as well as the recommendations for vitamin D supplementation in these patients. Despite the excitement raised by many data obtained about vitamin D and its influence on several aspects of the disease, further well-designed perspective trials are required to define the exact role that vitamin D may have in the management of both SLE and jSLE.

Increased Insulin Resistance and Glucagon Levels in Mild/Inactive Systemic Lupus Erythematosus Patients Despite Normal Glucose Tolerance.

To assess insulin sensitivity in patients with systemic lupus erythematosus (SLE) in response to a meal tolerance test (MTT). In this cross-sectional study, 33 adult females with mild/inactive SLE (SLE group) and 16 age- and body mass index-matched female healthy controls (CTRL group) underwent an MTT and were assessed for insulin sensitivity and beta cell function. Skeletal muscle protein expressions of total and membrane insulin-dependent glucose transporter 4 (GLUT-4) were also evaluated (SLE group: n = 10, CTRL group: n = 5); muscle biopsies were performed after MTT. Further measurements included inflammatory cytokines, adipocytokines, physical activity level, body composition, and food intake. SLE and CTRL groups showed similar fasting glucose, glucose response, and skeletal muscle GLUT-4 translocation after MTT. However, the SLE group demonstrated higher fasting insulin levels (P = 0.01; effect size [ES] 1.2), homeostatic model assessment insulin resistance (IR) (P = 0.03; ES 1.1), insulin-to-glucose ratio response to MTT (P = 0.02; ES 1.2), fasting glucagon levels (P = 0.002; ES 2.7), glucagon response to MTT (P = 0.0001; ES 2.6), and a tendency toward lower Matsuda index of whole-body insulin sensitivity (P = 0.06; ES -0.5) when compared with the CTRL group. Fasting proinsulin-to-insulin ratio and proinsulin-to-insulin ratio response to MTT were similar between groups (P > 0.05), while the SLE group showed a higher insulinogenic index when compared with the CTRL group (P = 0.02; ES = 0.9). We have identified that SLE patients had a bi-hormone metabolic abnormality characterized by increased IR and hyperglucagonemia despite normal glucose tolerance and preserved beta cell function and skeletal muscle GLUT-4 translocation. Strategies capable of ameliorating insulin sensitivity to reduce the risk of type 2 diabetes mellitus and cardiovascular disease in SLE may require more than targeting IR alone.

Endothelial dysfunction is associated with activation of the type I interferon system and platelets in patients with systemic lupus erythematosus

ObjectivesEndothelial dysfunction may be connected to cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). Type I interferons (IFNs) are central in SLE pathogenesis and are suggested to induce both endothelial...