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)

Systemic lupus erythematosus (SLE) patients have increased cardiovascular morbidity and mortality. QT-interval parameters are presumed markers of cardiovascular risk and have not been previously evaluated in SLE. Standard 12-lead ECGs were obtained from 140 female SLE outpatients and 37 age and body mass index-matched controls. QT interval was measured in each lead and heart rate-corrected maximum QT-interval duration (QTcmax) and QT-interval dispersion (QTd) were calculated. Risk factors for cardiovascular disease and lupus clinical features, disease treatment, disease activity and damage index were recorded. SLE patients have increased QT-interval parameters when compared to controls (QTcmax: 427.91 +/- 31.53 ms(1/2) versus 410.05 +/- 15.45 ms(1/2), P < 0.001; QTd: 52.38 +/- 22.21 ms versus 37.12 +/- 12.88 ms, P < 0.001). These differences persisted after excluding those patients with arterial hypertension, diabetes and with ECG abnormalities (QTcmax: 419.90 +/- 28.78 ms(1/2) versus 409.15 +/- 15.85 ms(1/2), P = 0.041; QTd: 54.74 +/- 26.00 ms versus 37.96 +/- 13.05 ms, P = 0.001). Multivariate linear regression for factors associated with QTcmax selected the presence of electrocardiographic left ventricular hypertrophy (ECG-LVH) (P = 0.003), nonspecific ST-T-wave abnormalities (P = 0.022) and left atrial enlargement (P = 0.044). Multivariate associates with QTd were age (P = 0.018), ECG-LVH (P = 0.022) and ST-T abnormalities (P = 0.031). In conclusion, SLE patients have increased QT interval parameters when compared to controls. This prolongation may lead to an increased cardiovascular risk. This finding might be due to subclinical atherosclerotic cardiovascular disease.
Lupus 2005
PMID:QT-interval parameters are increased in systemic lupus erythematosus patients. 1630 81

Atherosclerosis, a major cause of disease and death from cardiovascular disease (CVD), is an inflammatory disease characterized by T cell and monocyte/macrophage infiltration in the intima of large arteries. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in systemic lupus erythematosus (SLE), often considered a prototypic autoimmune disease. A combination of traditional and non-traditional risk factors, including dyslipidemia, inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. aPL are highly thrombogenic, and possible mechanisms include direct effects of aPL on endothelial and other cells, and interference with coagulation reactions. More than a thousand proteins of the annexin-superfamily are expressed in eukaryotes. Annexins are ubiquitous, highly conserved, predominantly intracellular proteins, widely distributed in tissues. Annexin A5 (ANXA5) is an important member of the annexin family due to its antithrombotic properties. These are believed to be caused by it forming a two-dimensional protective shield, covering exposed potentially thrombogenic cell surfaces. Recently, ANXA5 has been implicated in SLE since aPL interfere with ANXA5 binding to placental trophoblasts, causing microthrombosis and miscarriage, a rather common complication in SLE. We recently demonstrated that ANXA5 may play a role in CVD and is abundant in late-stage atherosclerotic lesions. Sera from SLE-patients with a history of CVD inhibited ANXA5 binding to endothelium, caused by IgG antibodies, to a significant degree aPL. This review will focus on potential involvement of ANXA5 in pathogenesis of CVD, particularly caused by underlying atherosclerosis and atherothrombosis.
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PMID:Annexin A5 in cardiovascular disease and systemic lupus erythematosus. 1632 95

Accelerated atherosclerotic cardiovascular disease is increasingly recognized as a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Cardiac manifestations of SLE are frequent and can involve almost all components of the heart. Pulmonary hypertension often develops during the course of SLE. The high incidence of cardiovascular complications may justify a screening of SLE patients in order to ensure early diagnosis and therapy. Results of diagnostic procedures that detect coronary insufficiency, surrogates of atherosclerotic burden and echocardiographic findings are often abnormal in SLE. However, evidence to support a routine screening for cardiovascular disease is currently not available. Therefore, based on the recommendations that have been proposed for other conditions associated with cardiovascular disease, we suggest assessment of risk factors and the performance of echocardiography at least annually in asymptomatic SLE patients. If two or more risk factors are present, an exercise ECG is recommended. The benefit, however, of screening SLE patients for cardiovascular disease has to be confirmed in prospective studies.
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PMID:[Cardiovascular monitoring of patients with systemic lupus erythematosus]. 1632 62

Mounting evidence from a growing body of epidemiologic studies demonstrates that patients with systemic lupus erythematosus (SLE) are at increased risk for the development of premature cardiovascular disease (CVD). However, awareness of accelerated atherosclerosis in young SLE patients, albeit growing, is still limited, as documented by the brief case presented. Inflammation is thought to play an important role in both the pathogenesis of SLE, as well as atherosclerotic vascular disease. Inflammatory processes that are shared by SLE and atherosclerotic disease include immune complex deposition and fixation, autoantibody binding, complement activation and CD40-CD40 ligand interaction. By examining the inflammatory mechanisms in common between SLE and atherosclerotic disease, we can come to a better understanding of the pathophysiology of the accelerated atherosclerotic process seen in patients with SLE and can gain insights into developing and instituting preventative and treatment strategies. In this article, we present a case of a young woman with SLE who presents with chest pain, followed by a review of inflammation-based pathogenic mechanisms that are shared by SLE and atherosclerotic cardiovascular disease.
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PMID:Premature atherosclerotic disease in systemic lupus erythematosus--role of inflammatory mechanisms. 1643 36

Oxidative stress and LDL modification (oxLDL) are early pro-atherogenic events. OxLDL binds beta2GPI producing immunogenic oxLDL/beta2GPI complexes. Antibodies to these complexes have been associated with arterial thrombosis in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Circulating oxLDL/beta2GPI complexes, IgG and IgM antibodies to these complexes were measured by ELISA in 30 SLE patients asymptomatic for cardiovascular disease (mean age 31 years) and 27 age/sex matched healthy controls. Carotid intima-media thickness (IMT) was measured by ultrasound in all patients and controls. Forty-seven percent of SLE presented plaques (median IMT of 0.65 +/- 0.12 mm) while only 7% of the controls had plaques (median IMT of 0.50 +/- 0.04 mm, P < 0.001). Median optical density (OD450nm) for oxLDL/beta2GPI complexes in SLE was 0.244 +/- 0.07, higher than controls (0.174 +/- 0.09, P < 0.001). Median OD for IgG anti-oxLDL/beta2GPI antibodies was also higher in SLE (0.297 +/- 0.26) compared to controls (0.194 +/- 0.07, P < 0.001) while the median OD for IgM antibodies in SLE (0.444 +/- 0.46) was not different than controls (0.326 +/- 0.22, P = 0.267). There was no correlation between IMT and oxLDL/beta2GPI complexes, IgG or IgM antibodies, possibly reflecting the complex interrelationship between these serologic elements and tissue factors in the arterial wall. These results support the hypothesis that oxLDL/beta2GPI complexes and IgG (not IgM) anti-oxLDL/beta2GPI antibodies contribute to the development of autoimmune-mediated atherosclerosis.
Lupus 2006
PMID:Oxidized low-density lipoprotein and beta2-glycoprotein I in patients with systemic lupus erythematosus and increased carotid intima-media thickness: implications in autoimmune-mediated atherosclerosis. 1653 78

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). In addition to systemic inflammation, additional mechanisms have been put forward that are more specific for the pathophysiology of the individual chronic inflammatory disorders.
Lupus 2006
PMID:Atherogenesis in rheumatology. 1663 62

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

Free radical-mediated oxidative damage and consequent protein modification by the end products of oxidative damage are important mediators of cell toxicity and disease pathogenesis. Aldehydic products, mainly the 4-hydroxy-2-alkenals, form adducts with proteins and make them highly immunogenic. Oxidative modification of proteins has been shown to elicit antibodies in a variety of diseases including systemic lupus erythematosus (SLE), alcoholic liver disease, diabetes mellitus (DM), and rheumatoid arthritis (RA). Oxidatively modified DNA (8-oxodeoxyguanine) and low-density lipoproteins (LDL) occur in SLE, a disease in which premature atherosclerosis is a serious problem. In addition, immunization with 4-hydroxy-2-nonenal (HNE)-modified 60-kDa Ro autoantigen elicits an accelerated epitope spreading in an animal model of SLE. Advanced glycation end product (AGE) pentosidine and AGE-modified IgG have been shown to correlate with RA disease activity. Oxidatively modified glutamic acid decarboxylase is important in type 1 DM, while autoantibodies against oxidized LDL are prevalent in Behcet's disease. The fragmentation of scleroderma-specific autoantigens occurs as a result of oxidative modification and is thought to be responsible for the production of autoantibodies through the release of cryptic epitopes. In the face of overwhelming evidence for the involvement of oxidative damage in autoimmunity the administration of antioxidants is a viable untried alternative for preventing or ameliorating autoimmune disease, although results in cardiovascular disease are disappointing.
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PMID:Oxidatively modified autoantigens in autoimmune diseases. 1686 87

Systemic lupus erythematosus (SLE) is associated with severe and premature cardiovascular disease, which cannot be explained by traditional risk factors alone. This study aims to investigate novel cardiovascular risk factors and cardiac event predictors in inactive SLE female patients who do not have any major cardiovascular risk factors. Twenty-five inactive (SLE disease activity index score <4) SLE female patients and 22 healthy control women were studied. SLE patients with a history of diabetes mellitus, hypertension, hyperlipidemia, smoking, or coronary artery disease (CAD) were excluded. Venous blood samples were analyzed for lipid subfractions and novel cardiovascular risk factors such as lipoprotein (a), homocysteine, fibrinogen, high-sensitivity C-reactive protein (hs-CRP), and serum amyloid A (SAA) levels. Endothelial dysfunction was assessed by flow-mediated dilatation (FMD) from the brachial artery at baseline and during reactive hyperemia. SLE patients and controls were similar in terms of age (40+/-10 years vs 38+/-10 years, p = NS). No significant difference was found between the groups regarding family history of premature CAD, blood pressure, body mass index, lipoprotein (a), homocysteine, fibrinogen, SAA, apoprotein A-1 and B levels. Compared with the controls, SLE patients had higher levels of hs-CRP [median (range): 1.82 (0.02-0.98) vs 0.68 (0.02-0.35), p=0.04]. FMD was lower in SLE patients than controls (7.1+/-2.1 vs 11.4+/-1.2%, p<0.001). Increased levels of hs-CRP and decreased FMD were found in inactive SLE patients. Increased hs-CRP levels may reflect ongoing low-grade inflammation that could be a cause of impaired FMD in SLE patients. These findings suggest that SLE patients without traditional major cardiovascular risk factors may have increased risk of cardiovascular disease and future cardiac events.
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PMID:Novel cardiovascular risk factors and cardiac event predictors in female inactive systemic lupus erythematosus patients. 1690 27

Atherosclerosis is a pathologic process affecting blood vessels, which leads to the development of cardiovascular disease. The immune system is involved in atherogenesis and in the pathogenesis of atherosclerosis. Several autoimmune rheumatic conditions, including rheumatoid arthritis, systemic lupus erythematosus and antiphospholipid syndrome, are characterized by enhanced atherosclerosis and consequently higher cardiovascular morbidity and mortality rates. Enhanced atherosclerosis, in these diseases, can manifest as overt cardiovascular diseases, but could be detected at an earlier stage by identification of abnormal endothelial function and arterial intima-media thickening. Both classical and nonclassical risk factors are presumed to contribute to atherosclerosis progression in rheumatic diseases. As atherosclerosis can be considered to be an immune-mediated process, several experimental strategies exist for its immunomodulation, including induction of immune tolerance. In this article, we briefly review the contribution of autoimmune elements, such as autoreactive lymphocytes and autoantibodies to atherosclerosis and discuss the nature of atherosclerosis in autoimmune rheumatic diseases.
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PMID:Mechanisms of disease: atherosclerosis in autoimmune diseases. 1693 63


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