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)

Mental stress has an enormous impact on physical health. This impact commonly manifests as headache, muscle tension, acne, peptic ulcer disease, or a compromised immune system. Stress is also associated with more serious adverse effects, such as cardiovascular disease and exacerbations of rheumatoid arthritis and systemic lupus erythematosus. As these effects are far-reaching, it is important for primary care physicians to identify and manage the symptoms of mental stress in their patients. This is increasingly possible with office-based mental stress testing, which uses cardiovascular markers to identify patients who are overresponders to mental stress, and, thus, at risk for stress-induced disorders. Mental stress in this population can be managed with nonpharmacologic and pharmacologic interventions to improve patients' responses to stress and decrease morbidity and mortality associated with this condition.
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PMID:Evaluating the impact of stress on systemic disease: the MOST protocol in primary care. 1277 65

Atherosclerosis is the major cause of cardiovascular disease (CVD) and in addition to established risk factors as smoking, hypertension, diabetes and dyslipidemia, inflammation and autoimmune reactions have been much discussed recently. Several lines of evidence indicate that also inflammation and autoimmune reactions are highly relevant in atherosclerosis and CVD. Inflammatory cells and cytokines are present in lesions, already at an early stage; animal experiments suggest that immune reactions, though not necessary for development of atherosclerosis, can modulate disease development and systemic inflammation is associated with an enhanced risk of CVD. The enhanced risk of CVD in a major autoimmune disease, systemic lupus erythematosus (SLE), is therefore highly relevant, and in addition to being an important clinical problem, SLE-related CVD could give insights into the nature of autoimmunity in atherosclerosis and CVD in general. We recently defined traditional and non-traditional risk factors for CVD in SLE. These include increased atherosclerosis (as determined by intima-media thickness of carotid artery); raised oxidized low density lipoprotein (OxLDL) and autoantibodies to OxLDL; dyslipidemia with raised triglycerides and Lp(a) and decreased HDL-cholesterol concentrations; raised systemic inflammation; presence of anti-phospholipid antibodies including lupus anticoagulant, homocysteine-levels and more frequent osteoporosis. Disease duration, smoking, blood pressure or diabetes mellitus did not differ significantly between the groups. Taken together, immune reactions are highly relevant in atherosclerosis, and patients with autoimmune disease like SLE are at high-risk of CVD. If confirmed prospectively, non-traditional risk factors like OxLDL in the circulation, autoantibodies against OxLDL and phospholipids and inflammation could lead to new therapeutic strategies and insight into disease mechanisms.
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PMID:Autoimmunity, oxidized LDL and cardiovascular disease. 1284 1

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder affecting multiple organ systems. Treatment of the disease has contributed dramatically in the long-term survival of the patients and now SLE has become a chronic inflammatory disorder. Present data suggest 5, 10 and 20-year survival rates of 93%, 85% and 68% respectively. Accelerated atherosclerosis and early coronary artery disease have become important causes of death and hospitalisation in SLE patients. Many cardiovascular risk factors can be considered: disease activity (particularly kidney involvement), sedentary life (in nearly 70% of the patients), hyperlipidemia, antiphospholipid antibodies, serum homocysteine and many others. Although traditional risk factors are operative in patients with SLE, the risk for myocardial infarction was increased 8.3 folds after controlling these factors in a study, suggesting that SLE itself was the strongest risk factor for cardiovascular disease. Lipid abnormalities may play a major role in increasing cardiovascular risk in SLE patients who are characterized by elevated triglycerides, very low-density lipoprotein cholesterol (VLDL-C), reduced levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo) A-1. Anticardioli-pin antibodies may influence lipid levels in SLE; in particular SLE patients with IgG anticardiolipin antibodies had significantly lower HDL-C compared with patients with no anticardiolipin antibodies. Elevation of serum homocysteine is observed in 15% of SLE patients and is significantly associated with the development of stroke and arterial thrombotic events. The antiphospholipid syndrome (APS) is an acquired thrombotic disorder characterised by recurrent venous or arterial thrombosis or recurrent miscarriages, or both, associated with the presence in the serum of IgG or IgM anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LAC). APS may occur as a primary disorder (PAPS) or associated with connective tissue diseases, mainly systemic lupus erythematosus (secondary APS). Primary and secondary APS are both associated with a significant increase of cardiovascular risk.
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PMID:[Cardiovascular risk factors in systemic lupus erythematosus and in antiphospholipid syndrome]. 1285 54

Patients with systemic lupus erythematosus (SLE) are at high risk of cardiovascular disease (CVD). Tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathophysiological processes of both SLE and CVD. This study focuses on the role of TNF-alpha and its soluble receptors in SLE-related CVD. In summary, 26 women (52 +/- 8.2 years) with SLE and a history of CVD (SLE cases) we compared with 26 age-matched women with SLE and no clinical manifestations of CVD (SLE controls) and 26 age-matched population-based control women (population controls). Plasma concentrations of circulating TNF-alpha, TNF-alpha receptor 1 (sTNFR1) and TNF-a receptor 2 (sTNFR2) were determined by ELISA. TNF-alpha, sTNFR1 and sTNFR2 were raised in SLE cases as compared to SLE controls (P = 0.009; P = 0.001; P = 0.001, respectively), and SLE controls had higher levels than population controls (P = 0.001; P = 0.02; P = 0.001, respectively). Exclusively in the SLE case group there was a striking positive correlation between TNF-alpha and plasma triglycerides (r = 0.57, P < 0.002), VLDL triglycerides (r = 0.54, P = 0.004) and VLDL cholesterol (r = 0.58, P = 0.002). Furthermore, TNF-alpha correlated with the waist-hip ratio but not with estimated insulin resistance. TNF-alpha may thus be a major factor in SLE-related CVD acting both by contributing to hypertriglyceridaemia and by promoting atherosclerosis-related inflammation. sTNFR1 and sTNFR2 are strongly associated with CVD in SLE but their exact roles in disease development remain to be elucidated.
Lupus 2003
PMID:TNF-alpha: a link between hypertriglyceridaemia and inflammation in SLE patients with cardiovascular disease. 1287 47

Asymptomatic antiphospholipid antibody (aPL) carriers with high risk for thrombosis may benefit from preventive anticoagulation. It was our objective to test whether the risk of thrombosis increases with: 1). increasing titres of anticardiolipin antibodies (aCL) after adjustment for other cardiovascular risk factors and 2). the number of aPL detected. In a cross-sectional study, blood was collected from clinics in two teaching hospitals. The study included 208 individuals suspected of having an aPL and 208 age- and sex-matched controls having blood drawn for a complete blood count. Clinical variables included history of previous arterial (ATE) or venous (VTE) thrombotic events, traditional risk factors for cardiovascular disease, and systemic lupus erythematosus (SLE). Laboratory variables included IgG/IgM aCL, lupus anticoagulant, and IgG/IgM anti-beta2-glycoprotein I. Mean age was 46.5 years and 83% were female. Seventy-five of the 416 participants had >or= 1 aPL, and 69 had confirmed >or= 1 ATE or VTE. Family history was positive in 48% of participants, smoking in 28%, hypertension in 16%, diabetes in 6%, and SLE in 20%. A 10-unit increase in aCL IgG titre was associated with an odds ratio (OR) [95% CI] of 1.07 [1.01-1.13] for ATE and 1.06 [1.02-1.11] for VTE. The odds of a previous thrombosis increased with each additional aPL detected: 1.5 [0.93-2.3] for ATE and 1.7 [1.1-2.5] for VTE. These results indicate that increased titres of aCL and multiple aPL were associated with an increased risk of a previous thrombotic event.
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PMID:Thromboembolic risk in patients with high titre anticardiolipin and multiple antiphospholipid antibodies. 1287 33

Atherosclerosis may be considered an inflammatory disease characterised by the development of atherosclerotic plaques and ischaemic cardiovascular events. Increased prevalence of cardiovascular morbidity and mortality due to (premature) atherosclerosis has been observed in patients with autoimmune diseases like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Wegener's granolumatosis. This increased prevalence cannot be explained by the presence of the traditional cardiovascular risk factors such as hypertension, hyperlipidaemia, diabetes mellitus and smoking. Therefore, other risk factors must be present in patients with systemic autoimmune disease. Although the mechanisms have not been fully unravelled, endothelial cell (EC) activation through autoantibodies seems to be one of the factors involved. EC activation results in EC dysfunction. It is supposed that chronic EC dysfunction, as present in patients with systemic autoimmune disorders, contributes to the development of premature atherosclerosis and results in an increased prevalence of cardiovascular disease.
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PMID:Endothelial activation, endothelial dysfunction and premature atherosclerosis in systemic autoimmune diseases. 1469 39

Major histocompatibility complex (MHC) class II molecules are up-regulated on endothelial cells in human allografts, and are thought to be involved in graft rejection. The MHC class II subtypes HLA-DR, DQ and DP regulate T cell dependent immune responses, and aberrant expression could be important in autoimmunity. Increased endothelial MHC class II expression has been demonstrated in several autoimmune diseases, including myocarditis with dilated cardiomyopathy, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Recent data suggest that there is an association between endothelial expression of MHC class II molecules and diffuse endothelial dysfunction, which may be part of the explanation of the increased risk of cardiovascular disease in patients with RA, SLE and other chronic inflammatory conditions. MHC class II transcription is in part genetically determined. Cytokine induced up-regulation of MHC class II molecules can be inhibited in vitro by antioxidants and different drugs, such as cyclosporin and statins. Research on the development of new treatments for systemic autoimmune diseases and cardiovascular disease should include evaluation of effects on endothelial activation, including MHC class II expression. This review also discusses the genetic basis of MHC class II expression and its implications for understanding MHC genotype associations with autoimmune diseases. Recent studies of interactions between endothelial cells and T cells are reviewed. Such interactions could be of major importance in the pathogenesis of autoimmune and vascular diseases.
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PMID:Endothelial expression of MHC class II molecules in autoimmune disease. 1475 93

Systemic lupus erythematosus is a heterogeneous, multisystem disease responsive to treatment with corticosteroids and immune suppressives. Many patients fail to achieve treatment-free remissions, and their long-term outcomes remain poor owing to the development of vital organ failure, cumulative drug toxicity and an increased risk of cardiovascular disease and malignancy. Haematopoietic stem cell transplantation (HSCT) offers the potential to improve long-term outcome in those with a poor prognosis. Preliminary phase II and registry studies have usually employed non-myeloablative conditioning with positive CD34 cell selection. They have highlighted the potential efficacy and dangers of HSCT. Patient selection is important but complex, and the influence of HSCT on long-term outcome is unknown. Disease relapse occurs in up to one-third of patients after HSCT, but the consequences of relapse and the role of remission-maintenance strategies are unknown. With the availability of other alternative therapies in refractory disease, there needs to be a clear demonstration of the benefits of HSCT from current randomized trials.
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PMID:Stem cell transplantation in systemic lupus erythematosus. 1530 41

The heart is one of a number of organs that may be affected in systemic lupus erythematosus (SLE), a prototypic autoimmune disease. Potential anatomical sites of involvement include the myocardium, pericardium, endocardium, valves, conduction system and blood vessels that subserve the heart. Typically, the severity of cardiovascular disease in lupus correlates with the degree of systemic inflammation, which is mirrored by the level of C-reactive protein (CRP) in the plasma. C-reactive protein, in turn is regulated by proinflammatory cytokines, such as interleukins (ILs) 1beta and 6. These cytokines have been found in functionally and/or structurally damaged areas of the heart and have been implicated in disease pathogenesis. It has been assumed that the source of these putatively pathogenetically relevant cytokines in the compromised heart is infiltrating mononuclear cells. This study tests the hypothesis that cardiomyocytes per se may contribute to proinflammatory cytokine production in the setting of systemic inflammation. Using as the experimental model MRL/MpJ-Tnfrs6(lpr) (MRL-lpr/lpr) mice, which spontaneously manifest an autoimmune syndrome that has clinical features of SLE, we show that ventricular homogenates and ventricular cardiomyocytes constitutively overexpress genes encoding the proinflammatory cytokines IL-1beta, IL-6, IL-10, and gamma interferon. The results suggest the possibility that proinflammatory cytokines emanating from the heart may actually contribute to the high levels of CRP that appear to aid in predicting subsequent cardiac events. Viewed in this setting, CRP becomes a footprint of an ongoing pathogenic process mediated, in part, by the heart muscle itself.
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PMID:Proinflammatory cytokine genes are constitutively overexpressed in the heart in experimental systemic lupus erythematosus: a brief communication. 1538 94

While modern treatments for systemic lupus erythematosus (SLE) have resulted in greatly improved long term outcome in children and adults, complications of atherosclerosis have become a major cause of morbidity and mortality. Although children and adolescents with SLE rarely experience adverse cardiovascular events before adulthood, dyslipoproteinemia and early evidence of premature atherosclerosis is present much earlier. Accelerated atherogenesis in SLE is multifactorial, most likely reflecting vascular, immune, and inflammatory changes along with medication effects. The long term complications of cardiovascular disease in childhood lupus present a particularly important target for intervention because of the potential return on investment by significantly lengthening life and improving quality of life over many decades. An ongoing multi-center, randomized, controlled trial, Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE), testing the efficacy of statins in preventing premature atherosclerosis in children and adolescents with SLE will guide future therapeutic intervention.
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PMID:Dyslipoproteinemia and premature atherosclerosis in pediatric systemic lupus erythematosus. 1552 1


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