Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High LDL and/or low HDL are risk factors for atherosclerosis and are also a common clinical feature in systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. Here, we show that changes in lipid profiles that reflect atherosclerotic disease led to activation of skin murine dendritic cells (DCs) locally, promoted dermal inflammation, and induced lymph node hypertrophy. Paradoxically, DC migration to lymph nodes was impaired, suppressing immunologic priming. Impaired migration resulted from inhibitory signals generated by platelet-activating factor (PAF) or oxidized LDL that acts as a PAF mimetic. Normal DC migration and priming was restored by HDL or HDL-associated PAF acetylhydrolase (PAFAH), which mediates inactivation of PAF and oxidized LDL. Thus, atherosclerotic changes can sequester activated DCs in the periphery where they may aggravate local inflammation even as they poorly carry out functions that require their migration to lymph nodes. In this context, HDL and PAFAH maintain a normally functional DC compartment.
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PMID:Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization. 1548 33

To determine the prevalence of dyslipoproteinemia on a large juvenile systemic lupus erythematosus (jSLE) cohort, we selected 40 patients after rigorous exclusion criteria. Lipoprotein levels were determinated after 12 hours fast and risk levels for CAD were defined by standards of the Brazilian Guidelines for dyslipoproteinemia according to US-NCEP. All individuals were under steroid therapy and chloroquine and 43% had active disease. Thirty patients (75%) had high-risk levels for CAD (23 isolated low HDL, while in seven subjects low HDL was associated to high TG in four, high LDL in one, high TG/LDL in one and high TC/LDL in one). Remarkably, overall analysis revealed that 85% patients were included in high/medium risk levels group (29% for TC, 29% for LDL, 88% for HDL, and 18% for TG) and these disturbances occured mainly in the first four years of disease. Unexpectedly, one-third of the patients presented two or more high/medium lipoprotein risk factors. Independently, active jSLE was associated to TG (OR = 3.2; P < 0.001) and had a tendency towards reduction on HDL (OR = 8.5; P = 0.056). Considering improvements on jSLE outcome, the increased frequency of high/medium lipoprotein risk levels for CAD reinforces the need of prevention measures in order to minimize deleterious effects of this disturbance.
Lupus 2005
PMID:The frequency of high/moderate lipoprotein risk factor for coronary artery disease is significant in juvenile-onset systemic lupus erythematosus. 1617 33

Dyslipoproteinemia is common in lupus patients. In this study, we investigated the pattern of dyslipoproteinemia in the course of active systemic lupus erythematosus (SLE) in possible association with anti-double-stranded DNA (anti-dsDNA) antibodies. Forty-six lupus patients under 45 years old who fulfilled the American College of Rheumatology revised criteria for the classification of SLE were selected. The exclusion criteria were renal failure, nephrotic syndrome, thyroid or liver disease, diabetes mellitus, obesity, pregnancy and taking drugs that induce dyslipidemia. Disease activity was measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Comparison of the lipid profiles, between active and inactive groups determined high levels of serum TG and VLDL and low levels of serum HDL in active group in comparison with inactive group (P < 0.05). The results indicated that the levels of TG and VLDL were significantly elevated in the patients with positive anti-dsDNA (P < 0.05). Although, the mean of serum HDL levels was also lower in patients with positive anti-dsDNA, the difference was not significant. This pattern of dyslipoproteinemia in active SLE may be associated with the autoimmune mechanisms especially in relation to the presence of anti-dsDNA antibodies.
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PMID:Dyslipoproteinemia during the active course of systemic lupus erythematosus in association with anti-double-stranded DNA (anti-dsDNA) antibodies. 1694 55

Toward the end of the last century a better knowledge of cardiovascular (CV) risk factors and their associations led investigators to propose the existence of a unique pathophysiological condition called "metabolic" or "insulin resistance syndrome". Among all, insulin-resistance and compensatory hyperinsulinemia are considered its most important treatment targets. Different definitions have been provided by World Health Organization (WHO) and by The Third Report of The National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP III). In particular, abdominal obesity, hypertension, low HDL cholesterol and hyperglicemia are the most common items used for its definition. The presence of MetS is effective in predicting the future risk of diabetes and coronaropathies. The evidence of a higher CV risk rate among different rheumatic inflammatory diseases has recently been associated with high prevalence of MetS in some cases. Rheumatoid or psoriatic arthritis have the large series among arthritis, whereas systemic lupus erythematosus among connective tissue disorders. This review analyses all most important studies about the evidence of MetS in rheumatic patients and the main clinical and prognostic significance of this relation.
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PMID:[Metabolic syndrome in inflammatory rheumatic diseases]. 1701 32

The association of SLE with atherosclerosis suggests a common pathogenic mechanism. SLE and atherosclerosis are immune complex-mediated diseases. The integration of metabolism and immunity, which under normal conditions is beneficial for the maintenance of good health, can become deteriorative under conditions of metabolic challenge, as exemplified by the immunosuppression characteristic of malnourished or starving individuals. It is now apparent that obesity is associated with a state of chronic inflammation, particularly in white adipose tissue. However, in the absence of obesity, infusion of animals with inflammatory cytokines or lipids can cause insulin resistance. It is possible that the stresses of obesity are similar enough to the stresses of an infection and the body reacts to obesity as it would to an infection. Atherosclerosis can be considered to have a significant chronic inflammatory component. Inflammation also contributes to the typical dyslipidemia associated with SLE that is characterized by elevations of VLDL, LDL and triglycerides as well as reduced HDL. The link between insulin resistance and SLE can be explained by the chronic inflammatory state, and the consequent dyslipoproteinemia.
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PMID:Insulin resistance, chronic inflammatory state and the link with systemic lupus erythematosus-related coronary disease. 1711 Mar 17

To establish a mouse model of accelerated atherosclerosis in lupus, we generated apolipoprotein E-deficient (apoE(-/-)) and Fas(lpr/lpr) (Fas(-/-)) C57BL/6 mice. On a normal chow diet, 5 month old apoE(-/-)Fas(-/-) mice had enlarged glomerular tuft areas, severe proteinuria, increased circulating autoantibody levels, and increased apoptotic cells in renal and vascular lesions compared with either single knockout mice. Also, double knockout mice developed increased atherosclerotic lesions but decreased serum levels of total and non-HDL cholesterol compared with apoE(-/-)Fas(+/+) littermates. Moreover, female apoE(-/-)Fas(-/-) mice had lower vertebral bone mineral density (BMD) and bone volume density (BV/TV) than age-matched female apoE(-/-)Fas(+/+) mice. Compared with apoE(-/-)Fas(+/+) and apoE(+/+)Fas(-/-) mice, apoE(-/-)Fas(-/-) mice had decreased circulating oxidized phospholipid (OxPL) content on apoB-100 containing lipoprotein particles and increased serum IgG antibodies to OxPL, which were significantly correlated with aortic lesion areas (r = 0.58), glomerular tuft areas (r = 0.87), BMD (r = -0.57), and BV/TV (r = -0.72). These results suggest that the apoE(-/-)Fas(-/-) mouse model might be used to study atherosclerosis and osteopenia in lupus. Correlations of IgG anti-OxPL with lupus-like disease, atherosclerosis, and bone loss suggested a shared pathway of these disease processes.
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PMID:ApoE-/-Fas-/- C57BL/6 mice: a novel murine model simultaneously exhibits lupus nephritis, atherosclerosis, and osteopenia. 1725 98

To determine the prevalence of dyslipoproteinemias and their related factors in a Brazilian systemic lupus erythematosus (SLE) population, fasting lipids were measured in 185 female SLE outpatients. Age, BMI, smoking, post-menopausal status, presence of diabetes and hypertension, SLE duration, number of ARA criteria, drug treatment and disease activity (by SLEDAI) were registered. Statistics included uni and multivariate logistic regression. Eighty-nine patients (48.1%) had hypercholesterolemia, 55 (29.7%) had hypertriglyceridemia and 109 (58.9%) had either. On multivariate analysis, 24-h proteinuria (OR = 2.08, 95% CI: 1.11-3.88), BMI (OR = 1.08, 95% CI: 1.01-1.16) and post-menopausal status (OR = 2.48, 95% CI: 1.25-4.92) were associated with hypercholesterolemia. Disease activity was related to low HDL-cholesterol (OR = 2.59, 95% CI: 1.20-5.58) and, in pre-menopausal patients, also to hypertriglyceridemia (OR = 1.16, 95% CI: 1.03-1.30). Antimalarial use was protective for hypertriglyceridemia (OR = 0.44, 95% CI: 0.22-0.90). In conclusion, the increased prevalence of dyslipoproteinemias is due to proteinuria, obesity and SLE activity. Antimalarials have beneficial effect on lipid profile that may be due to reduction in disease activity.
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PMID:Prevalence and factors associated with dyslipoproteinemias in Brazilian systemic lupus erythematosus patients. 1778 49

Excessive lipid peroxidation is a major factor of accelerated atherosclerosis, observed in patients with systemic lupus erythematosus (SLE). We aimed at the present study to determine the paraoxonasel (PON1) and arylesterase activities, and lipid-profile in 37 SLE patients and 30 age-/sex-matched controls. Association was analyzed between PON1 activity and SLEDAI, CRP, anti-oxLDL, and antiphospholipid antibody (aPL) levels, steroid dose, and atherothrombotic events. The age of patients was 40.8 +/- 13.9 year, follow-up time 6.7 +/- 6.2 year, SLEDAI 2 (0-15). PON1 and arylesterase activities were measured spectrophotometrically using paraoxon and phenyl acetate as substrates, respectively. Phenotypic distribution of PON1 was determined by dual substrate method. We measured antioxLDL and aPL levels by ELISA, the CRP by automated immunoassay. PON1 activity (121.9 +/- 65.9 U/mL) was reduced significantly (P < 0.001) in SLE as compared to control (188.1 +/- 78.9 U/mL), but arylesterase activity was not different. A negative correlation was found between PON1 activity and age. PON1 activity did not correlate with other measured parameters. Reduced PON1 activity associated with clinical atherothrombotic complications (P < 0.01). High activity BB phenotype was not present in SLE. Lipid parameters (TC, LDL-C, HDL-C, ApoAI, and ApoB) were within normal range in both groups. Results indicated reduced PON1 activity in lupus patients despite long disease duration and low inflammatory activity, and it was evidenced as a risk for atherosclerotic complications. As the arylesterase activity was normal, further examinations are required to find other mechanisms, such as anti-PON1 antibodies, genetic polymorphisms, and difference in distribution of HDL-subfractions or enzyme abnormalities in HDL remodeling.
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PMID:Reduced paraoxonase1 activity is a risk for atherosclerosis in patients with systemic lupus erythematosus. 1789 73

The aim of this study was to evaluate traditional risk factors for coronary artery disease (CAD), homocysteine, anti-oxidized low-density lipoprotein (anti-oxLDL), anti-lipoprotein lipase (anti-LPL) and endothelin-1 (ET-1) in patients with primary anti-phospholipid syndrome (APS), furthermore verify possible association among these variables and arterial thrombosis. Thirty-eight women with primary APS and 30 age-and-sex-matched controls were evaluated. Patients presented higher-LDL and triglycerides levels and lower-HDL levels than controls. Anti-LPL antibodies were not detected in both groups. The mean number of risk factors was higher in patients than in controls (P = 0.030). Anti-oxLDL antibodies, homocysteine and ET-1 mean levels were similar between groups, but abnormal homocysteine levels were found only among primary APS patients (P = 0.031). Hypertension and the presence of at least one risk factor for CAD were more prevalent in patients with arterial involvement than those without. Homocysteine levels and mean number of risk factors for CAD were significantly higher in patients with arterial thrombosis than controls. In a multivariate analysis hypertension was the only independently associated with arterial thrombosis (OR 14.8, 95% CI = 2.1-100.0, P = 0.006). This study showed that in primary APS patients other risk factors besides anti-phospholipid antibodies contribute for the occurrence of arterial events and the most important factor was hypertension.
Lupus 2007
PMID:Impact of hypertension and hyperhomocysteinemia on arterial thrombosis in primary antiphospholipid syndrome. 1789

Patients with systemic lupus erythematosus (SLE) have accelerated atherogenesis. A recent study suggested that Chlamydia pneumoniae infection might also be a contributing factor in the development of atherogenesis in patients with SLE. The objective of this study was to investigate the possible association of C. pneumoniae infection with markers of atherosclerosis in adolescents with SLE compared with age-matched healthy controls. History and exam focused on cardiovascular risk factors were obtained from 20 patients with SLE and 20 age- and sex-matched controls. Laboratory studies included serum lipid profile and high-sensitivity C-reactive protein (hsCRP). Detection of C. pneumoniae in peripheral blood mononuclear cells (PBMCs) and in nasopharyngeal swab specimens was performed. Carotid Intima-Media Thickness (CIMT) was determined by sonography in all subjects. C. pneumoniae DNA was not detected in PBMCs of any of the patients or controls. Nasopharyngeal cultures were also negative for C. pneumoniae in all patients. CIMT was slightly higher in the SLE group (0.48 +/- 0.049) compared with controls (0.454 +/- 0.041, p = 0.29). There was no significant difference between the two groups in body mass index, blood pressure, hsCRP, and serum cholesterol (total, LDL and HDL). Serum triglycerides were higher in the lupus group (p = 0.03). Children and adolescents with SLE might have accelerated atherosclerosis; however, we did not observe an association with C. pneumoniae infection in this population.
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PMID:Absence of Chlamydia pneumoniae and signs of atherosclerotic cardiovascular disease in adolescents with systemic lupus erythematosus. 1808 Jan 55


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