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)

Premature coronary heart disease has emerged as a major cause of morbidity and mortality in systemic autoimmune diseases. Recent epidemiologic and pathogenesis studies have suggested a great deal in common between the pathogenesis of prototypic autoimmune disease such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and that of atherosclerosis. Some of the most remarkable data in support of a link between autoimmunity and atherosclerosis comes from epidemiological studies of patients with autoimmune disorders (RA and SLE). Many epidemiologic observations have linked systemic inflammation with the cardiovascular events in autoimmune disease such as RA and SLE. Inflammation is increasingly being considered central to the pathogenesis of atherosclerosis and an important risk factor for vascular disease. Systemic inflammation may be regarded as accelerating the atherosclerotic process. Systemic levels of soluble inflammatory mediators such as C-reactive protein (CRP) have been associated with cardiovascular risk in the general population. CRP, or more specifically high sensitivity-hsCRP, is a marker of systemic inflammation that has been identified as a valid biomarker of cardiovascular risk. Furthermore, the immunomodulatory and anti-inflammatory actions of statins may affect their utility in the context of chronic inflammatory autoimmune disease. Thus, effective control or dampening of inflammation, with such agents, should be included in the therapeutic armamentarium of autoimmune diseases with the aim of protecting against cardiovascular disease.
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PMID:Inflammation: a pivotal link between autoimmune diseases and atherosclerosis. 1678 58

The objective of this study was to analyse whether primary antiphospholipid syndrome (PAPS) may precede and modify the characteristics of systemic lupus erythematosus (SLE). Out of the total 362 SLE patients in our service, 223 patients had antiphospholipid antibodies (aPL), of whom 110 met the criteria of antiphospholipid syndrome. In 26 cases (7.2%) PAPS appeared 5.5 years before the onset of lupus (PAPS+SLE Group). Their clinical findings were compared to lupus patients without (SLE only Group, n = 26) and with secondary APS (SLE+SAPS Group, n = 26). The prevalence of deep venous thrombosis, stroke/TIA, recurrent fetal loss, coronary heart disease and myocardial infarction was significantly higher in PAPS+SLE Group as compared to SLE only Group. The difference in prevalence of fetal loss (P = 0.014) between PAPS+SLE and SLE+SAPS Groups was also recorded. On comparison to PAPS+SLE Group, patients without APS (SLE only Group) were younger at onset of lupus, with more frequent flares and a higher prevalence of WHO type III/IV nephritis (P = 0.007), requiring higher doses of cyclophosphamide and corticosteroids. Lupus started in the form of PAPS in 7.2% of our SLE patients, who presented with more thrombotic and less inflammatory complications than in SLE patients without a prior or with a following secondary APS. Considering the long latency between the two diseases, PAPS may be a forerunner of lupus, but it may also coexist with SLE as an independent autoimmune disorder.
Lupus 2007
PMID:Primary antiphospholipid syndrome as the forerunner of systemic lupus erythematosus. 1757 33

Low serum paraoxonase1 (PON1) activity determined by paraoxon substrate is associated with coronary heart disease (CHD), diabetes and systemic lupus erythematosus (SLE) risk. In this investigation, we have examined the role of genetic variation in the PON3 gene in relation to PON1 activity and SLE risk in a biracial sample comprising 377 SLE patients and 482 controls from US whites and blacks. We genotyped six PON3 tagging single nucleotide polymorphisms (tagSNPs) and examined their associations with PON1 activity, SLE risk, antiphopholipid autoantibodies (APA), lupus nephritis, carotid vascular disease, and inflammation. With the exception of PON1 activity, no other significant associations were found with PON3 SNPs. Multiple regression analysis including all six PON3 tagSNPs and PON1/Q192R and L55M SNPs revealed significant association of PON1 activity with 4 SNPs: PON3/A10340C (p < 0.0001), PON3/A2115T (p = 0.002), PON1/L55M (p < 0.0001) and PON1/Q192R (p < 0.0001). These four SNPs explained 2%, 1%, 8% and 19% of the variation in PON1 activity, respectively. In summary, our new data indicate that genetic variation in the PON3 gene influences serum PON1 activity independently of the known effect of PON1 genetic variation. To our knowledge, this is the first study reporting the association of the PON3 gene variants with PON1 activity.
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PMID:Genetic variation in the paraoxonase-3 (PON3) gene is associated with serum PON1 activity. 1790 Feb 66

Inflammation plays a key role in the pathogenesis of a number of chronic inflammatory systemic diseases (CISDs), including psoriasis, rheumatoid arthritis, systemic lupus erythematosus and Crohn's disease, and also in the pathogenesis of atherosclerosis. CISDs and cardiovascular diseases, such as atherosclerosis, share common pathogenic features, and cardiovascular disease is an important cause of morbidity and mortality in patients with CISDs. Activated inflammatory cells and pro-inflammatory cytokines contribute to the development of psoriatic lesions and play an important role in the breakdown of atherosclerotic plaques. Psoriasis and atherosclerosis also have similar histological characteristics involving T cells, macrophages and monocytes. In particular, the extravasation of T cells through the epithelium is characteristic of both psoriatic and atherosclerotic plaques. Cardiovascular disease is an important cause of morbidity and mortality in patients with psoriasis, which is associated with an increased cardiovascular risk profile compared with the general population. Patients with psoriasis are at increased risk of arterial hypertension, coronary heart disease, hyperlipidaemia, obesity and type II diabetes, which are more prevalent than in control patients. This increased risk could be due to the effects of chronic inflammatory changes, particularly the infiltration of T cells and subsequent secretion of pro-inflammatory cytokines. Some drugs used in the treatment of cardiovascular disease, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and angiotensin-converting enzyme inhibitors have anti-inflammatory activity. In addition, systemic treatments for psoriasis may, by decreasing inflammation, reduce the risk of cardiovascular disease. It is suggested, therefore, that an integrated approach to the treatment of the inflammatory processes underlying both psoriasis and atherosclerosis may be beneficial in reducing cardiovascular risk in patients with psoriasis. The newer targeted biological therapies, such as efalizumab and infliximab, which offer the potential for long-term disease control in psoriasis, may be of particular use in this setting.
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PMID:Inflammation in atherosclerosis and psoriasis: common pathogenic mechanisms and the potential for an integrated treatment approach. 1870 Sep 10

Little is known about qualitative abnormalities of high-density lipoproteins (HDL) in systemic lupus erythematosus (SLE). We studied distribution and composition of HDL subclasses in 30 premenopausal women with uncomplicated SLE, and 18 controls matched for age and sex. Plasma and HDL lipids were determined by colorimetric enzymatic assays, HDL size distribution by native gradient polyacrylamide gel electrophoresis (PAGE) and apolipoproteins in HDL by sodium dodecyl sulphate denaturing PAGE. Compared with controls, SLE patients had significantly lower proportions of HDL(2b) (-14.7%) and higher proportions of HDL(3b) (+8.8%) and HDL(3c) (+23.3%). Cholesteryl ester (-18%) and apolipoprotein AI (-9%) were lower, whereas triglycerides (+32%) and apolipoprotein E (+27%) were higher in SLE HDL (P < 0.05; for all). In the whole population, stepwise regression analysis showed that only insulin concentrations (R(2) = 0.327) and plasma total apo AI (R(2) = 0.114) accounted independently to the variance in HDL size. This study shows that HDL distribution and composition are abnormal in non-complicated SLE patients. These HDL abnormalities have been reported to be associated to impaired atheroprotective properties of HDL and prevalence of coronary heart disease. Therefore, they may contribute to the premature atherosclerosis observed in young women with SLE.
Lupus 2008 Nov
PMID:High-density lipoproteins are abnormal in young women with uncomplicated systemic lupus erythematosus. 1885 21

Atherosclerosis is a chronic inflammatory disorder characterized by immune cell activation, inflammation driven plaque formation and subsequent destabilization. In other disorders of an inflammatory nature, the chronic inflammatory state per se has been linked to acceleration of the atherosclerotic process which is underlined by an increased incidence of cardiovascular disease (CVD) in disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphopholipid (Hughes) syndrome (APS). SLE is an autoimmune disease that may affect any organ. Premature coronary heart disease has emerged as a major cause of morbidity and mortality in SLE. In addition to mortality, cardiovascular morbidity is also markedly increased in these patients, compared with the general population. The increased cardiovascular risk can be explained only partially by an increased prevalence of classical risk factors for cardiovascular disease; it also appears to be related to inflammation. Inflammation is increasingly being considered central to the pathogenesis of atherosclerosis and an important risk factor for vascular disease. Recent epidemiologic and pathogenesis studies have suggested a great deal in common between the pathogenesis of prototypic autoimmune disease such as SLE and that of atherosclerosis.We will review traditional risk factors for CVD in SLE. We will also discuss the role of inflammation in atherosclerosis, as well as possible treatment strategies in these patients.
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PMID:Cardiovascular disease in systemic lupus erythematosus: the role of traditional and lupus related risk factors. 1993 86

Polyunsaturated fatty acids (PUFAs) form an important constituent of all the cell membranes in the body. PUFAs such as arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) form precursors to both pro-inflammatory and anti-inflammatory compounds. Low-grade systemic inflammation occurs in clinical conditions such as insulin resistance, hypertension, type 2 diabetes mellitus, atherosclerosis, coronary heart disease, lupus, schizophrenia, Alzheimer's disease, and other dementias, cancer and non-alcoholic fatty liver disease (NAFLD) that are also characterized by an alteration in the metabolism of essential fatty acids in the form of excess production of pro-inflammatory eicosanoids and possibly, decreased synthesis and release of anti-inflammatory lipoxins, resolvins, protectins and maresins. We propose that low-grade systemic inflammation observed in these clinical conditions is due to an imbalance in the metabolism of essential fatty acids that is more in favour of pro-inflammatory molecules. In this context, transgenic fat-1 mouse that is designed to convert n-6 to n-3 fatty acids could form an ideal model to study the altered metabolism of essential fatty acids in the above mentioned conditions. It is envisaged that low-grade systemic inflammatory conditions are much less likely in the fat-1 mouse and/or these diseases will run a relatively mild course. Identifying the anti-inflammatory compounds from n-3 fatty acids that suppress low-grade systemic inflammatory conditions and understanding their mechanism(s) of action may lead to newer therapeutic strategies.
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PMID:Transgenic fat-1 mouse as a model to study the pathophysiology of cardiovascular, neurological and psychiatric disorders. 2004 3

Atherosclerosis begins in childhood with the formation of fatty streaks. Early plaques can be found in adolescence and early coronary disease can be found in young adults. It has been suggested that early treatment may lead to great benefits in later life. This article is a narrative review of the role of lipid-lowering drug therapy in paediatric practice. Increased rates of atherosclerosis are known to occur in children with familial hypercholesterolaemia (FH), especially in homozygotes. There is evidence for the efficacy and safety of lipid-lowering therapies in children, particularly with respect to the effects of HMG-CoA reductase inhibitors (statins) on lipids and, to a limited extent, on other surrogate measures of atherosclerosis in patients with FH. Diagnosis of FH and its early treatment are recommended in all guidelines. Lipid-lowering drug therapy is recommended for the treatment of homozygous FH at all ages and from as young as 10 years of age for the treatment of heterozygous FH when there is a family history of very premature coronary heart disease (occurring at age <40 years). Controversy exists about other possible indications. Increased rates of atherosclerosis are seen in autoimmune disorders, including type 1 diabetes mellitus, systemic lupus erythematosus and Kawasaki's disease, and in transplant recipients. All evidence in these areas is derived by extrapolation from studies in adults. These disorders can be divided into those for which percutaneous coronary intervention is performed early and/or for which drugs used to treat the primary disorder increase the rate of atherosclerosis, and those for which this is not the case. In both cardiac transplantation and Kawasaki's disease, increased atherosclerosis can occur as a result of (i) disease-related vasculopathy; or (ii) increased restenosis secondary to interventions. Statins have a good evidence base for reducing rates of re-occlusion following coronary artery procedures, and this justifies their use in these settings. In renal transplantation, statins may have a role to play in patients with persistent dyslipidaemia and additional cardiovascular risk factors. In other disorders, such as type 1 diabetes, the disease process is atherogenic and thus statins may be justified in patients with a long history of disease (>10 years), poor control, and evidence of vascular or endothelial damage or additional cardiovascular risk factors. There is a role for lipid-lowering therapies in children at high risk of atherosclerosis, but the evidence base outside of FH is weak. Lipid-lowering therapy should be prescribed to all children with homozygous or severe heterozygous FH. Based on adult evidence, statin therapy should be considered in patients who have undergone coronary artery procedures or received cardiac transplants, in whom their primary role is to prevent vascular re-occlusion. In diseases associated with a chronic increased atherogenic risk, such as type 1 diabetes, statins should be considered in high-risk cases where additional cardiovascular risk factors are present. At present, the most important need is for trials to be performed in children using accepted surrogate endpoints to define whether lipid-lowering drug therapy is beneficial in this group.
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PMID:Hyperlipidaemia in paediatric patients: the role of lipid-lowering therapy in clinical practice. 2008 38

The metabolic syndrome (MetS) is a recently defined clustering of cardiovascular risk factors associated with increased insulin resistance and a high risk of developing type II diabetes mellitus. Systemic lupus erythematosus (SLE) is associated with an increased prevalence of the MetS and patients also show evidence of increased insulin resistance. Controversy remains, however, regarding the precise definition of the MetS and its exact role in predicting long-term coronary heart disease risk both in SLE and in the general population. The major benefit of identifying the MetS in patients with SLE is likely to be from highlighting patients for focused lifestyle interventions and helping to guide individualized therapeutic regimes that take into account cardiovascular risk.
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PMID:The metabolic syndrome in systemic lupus erythematosus. 2020 92

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are chronic autoimmune diseases associated with confirmed high risk of cardiovascular pathology. Most low-risk patients develop cardiovascular complications (CVC) with the involvement of traditional factors of limited diagnostic value which requires introduction of new efficacious methods for CVC prognostication. Reduced cardiac rhythm variability (CRV) along with increased levels of inflammation markers is an independent predictor of unfavourable outcome in patients with coronary heart disease, chronic cardiac insufficiency, diabetes mellitus, arterial hypertension, and metabolic syndrome; it may be a consequence of joint contribution of sympatic activation and inflammation to the development of atherothrombotic complications. This review is focused on the methods of CRV evaluation, possible mechanisms of mutual potentiation of autonomous nervous system disturbances and inflammatory process, factors responsible for cardiac autonomous dysfunction in RA and SLE. Much attention is given to the possibilities of correction of vegetative dysregulation of cardiac activity in patients with autoimmune diseases.
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PMID:[Prospects for the assessment of cardiac rhythm variability in patients with rheumatoid arthritis and systemic lupus erythematosus]. 2108 45


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