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)

Accelerated atherosclerosis is an emerging problem in patients with systemic lupus erythematosus (SLE). We planned an observational study to determine whether in patients with SLE carotid intima-media thickness (IMT) represents an early sign of accelerated atherosclerosis and to confirm that SLE adds to the traditional cardiovascular Framingham risk factors. Thirty females with SLE (age 18-65 years) underwent anamnestic, clinical, and laboratory evaluation and B-mode ultrasonography of carotid arteries, which provides a direct and noninvasive assessment of subclinical atherosclerosis. IMT measurements were performed on the right and left common carotid arteries 1.0 cm proximal to the carotid bulb and the mean IMT value was calculated with a dedicated software. The Framingham Point Score was also calculated for each subject. SLE patients showed a mean IMT value of 0.73 +/- 0.12 (SD) mm. This value is significantly (P < 0.05) higher than that reported for an age-matched healthy female control population (0.66 +/- 0.11 SD mm). A preliminary evaluation of the Framingham Point Score, estimating the 10-year risk for women to develop cardiovascular events, indicated an increased risk of early cardiovascular events in SLE patients. In our study we have shown that patients with SLE have an increased mean IMT value compared with a healthy females control. Moreover, the evaluation of the Framingham Point Score suggests that SLE is an additional risk factor for cardiovascular disease.
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PMID:Intima-media thickness: a marker of accelerated atherosclerosis in women with systemic lupus erythematosus. 1789 78

Epidemiological studies conducted over the past 25 years have provided ample support for the association of mild hyperhomocysteinemia (HHcy) with an elevated risk of atherothrombosis. Since autoimmune disorders (AD) are frequently associated with relevant and early signs of atherothrombotic damage not adequately explained by the traditional risk factors involved in the onset of cardiovascular disease (CVD), a large interest has been shown to the putative role of mild HHcy in this setting. On the basis of such considerations, we focused the attention on the relationship between homocysteine (Hcy) and CVD in patients affected with autoimmune diseases, reviewing the most recent literature data and also providing our original experience. Although the large amount of available studies clearly shows that HHcy represents a common finding in patients affected with several autoimmune diseases, the actual role of Hcy in the development of CVD in the course of AD is not clear yet, perhaps, with the only exception of the systemic lupus erythematosus. In the other conditions, the role of Hcy in the pathogenesis of vascular complications is still a matter of debate, as the result of conflicting reports and/or lack of an adequate body of investigation.
Lupus 2007
PMID:Hyperhomocysteinemia: a cardiovascular risk factor in autoimmune diseases? 1797 57

Circulating levels of adiponectin decrease with increasing visceral obesity and are lower in patients with type 2 diabetes, the metabolic syndrome, and cardiovascular disease compared with controls matched by body mass index. Several reports demonstrated anti-inflammatory effects of adiponectin. Because increased adipose tissue is associated with low-grade chronic inflammation and proinflammatory factors inhibit adiponectin production, the current hypothesis states that chronic inflammation associated with visceral obesity inhibits production of adiponectin, perpetuating inflammation. The negative correlation between adiponectin and markers of inflammation in the aforementioned conditions supports this hypothesis. In contrast with disorders typically associated with excess adiposity and positive energy balance, adiponectin levels are elevated--rather than decreased--in classic chronic inflammatory/autoimmune diseases that are unrelated to increased adipose tissue, such as rheumatoid arthritis, SLE, inflammatory bowel disease, type 1 diabetes, and cystic fibrosis. In these patients, adiponectin levels positively--rather than negatively--correlate with inflammatory markers. Furthermore, proinflammatory effects of adiponectin have been reported in tissues such as joint synovium and colonic epithelium. Thus, adiponectin is regulated in the opposite direction and may exert differential functions in classic versus obesity-associated inflammatory conditions. This article discusses this apparent paradox and presents possible alternative and/or complementary explanations.
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PMID:Adiponectin and inflammation: consensus and controversy. 1877 64

C-reactive protein CRP is an acute-phase protein known as a biomarker for inflammation. As such CRP levels have been traditionally used to detect and predict the outcome of infections inflammatory and necrotic processes and to monitor the efficacy of treatment in these conditions. With the development of high sensitivity assays CRP has resurfaced as a very strong predictor in cardiovascular disease and as a mediator of atherosclerosis. The Centers for Disease Control and American Heart Association have elaborated guidelines for the use of CRP in the primary prevention setting and in patients with stable coronary disease or acute coronary syndromes. CRP has been used for differentiation between Systemic Lupus Erythematosus activity and infection in individuals without serositis. More recently CRP has also elicited interest as a therapeutic option in lupus. Murine lupus models treated with CRP have been reported to present delayed Lupus onset decreased antibody levels enhanced survival and reversal of ongoing proteinuria. In this paper we reviewed the multiple roles of CRP particularly in lupus.
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PMID:C-Reactive protein and its implications in systemic lupus erythematosus. 1815 97

Platelets are an abundant source of CD40 ligand (CD154), an immunomodulatory and proinflammatory molecule implicated in the onset and progression of several inflammatory diseases, including systemic lupus erythematosus (SLE), diabetes, and cardiovascular disease. Heretofore considered largely restricted to activated T cells, we initiated studies to investigate the source and regulation of platelet-associated CD154. We found that CD154 is abundantly expressed in platelet precursor cells, megakaryocytes. We show that CD154 is expressed in primary human CD34+ and murine hematopoietic precursor cells only after cytokine-driven megakaryocyte differentiation. Furthermore, using several established megakaryocyte-like cells lines, we performed promoter analysis of the CD154 gene and found that NFAT, a calcium-dependent transcriptional regulator associated with activated T cells, mediated both differentiation-dependent and inducible megakaryocyte-specific CD154 expression. Overall, these data represent the first investigation of the regulation of a novel source of CD154 and suggests that platelet-associated CD154 can be biochemically modulated.
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PMID:Nuclear factor of activated T cells (NFAT) mediates CD154 expression in megakaryocytes. 1818 Mar 80

Basal C-reactive protein (CRP) is a heritable trait associated with long-term cardiovascular disease risk. Existing studies leave ambiguity over the key functional polymorphisms and fail to adjust for trans-acting effects. In a novel cohort of 285 Filipino systemic lupus erythematosus probands and their first-degree relatives, we quantified serum CRP and typed a dense map of CRP single-nucleotide polymorphisms (SNPs), along with SNPs in the interleukin-1 beta, interleukin-6 and apolipoprotein E genes. Ten CRP SNPs demonstrated association with basal CRP in a regression model (P=0.011-0.002). These delineated two haplotypes associated with high and low basal CRP expression (P=0.002). Differences in allele frequency were seen compared with Caucasian populations, enabling us to argue for an independent genetic effect from a phylogenetically distinct haplotype tagged by SNP rs1800947. We demonstrated an association between Apo epsilon 2 and higher basal CRP. Interleukin-6 genotype was associated with basal CRP, highlighting a role for acute-phase cytokines even in basal expression. Identifying these trans-acting variants may improve the use of basal CRP as a predictor cardiovascular risk, and increase our power to detect associations between CRP and disease.
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PMID:Genetic determinants of basal C-reactive protein expression in Filipino systemic lupus erythematosus families. 1821 63

Despite the increased prevalence of cardiovascular disease in patients with systemic lupus erythematosus (SLE), little is known about the role of high sensitivity C-reactive protein (hsCRP) or whether ethnicity, gender, anthropometric measures and treatment can alter hsCRP levels. We evaluated the effects of treatment and demographic, anthropometric and socio-economic variables on hsCRP levels in SLE. High sensitivity C-reactive protein levels were measured using an immunoturbidimetric assay in 610 patients from the Hopkins Lupus Cohort, who were followed-up regularly. In stepwise multiple regression analyses, body mass index (BMI) [odds ratio (OR) 1.72, 95% confidence interval (CI) 1.34-2.20, P < 0.001], African-American ethnicity (OR 1.97, 95% CI 1.22-3.19, P < 0.01), education (OR 0.60, 95% CI 0.42-0.86, P < 0.01), statin use (OR 0.38, 95% CI 0.18-0.82, P < 0.05), estrogen use (OR 3.65, 95% CI 1.19-11.22, P < 0.05), SLE Disease Activity Index score (OR 1.76, 95% CI 1.09-2.87, P < 0.05) and cumulative prednisone dose (OR 1.27, 95% CI 1.01-1.60, P < 0.05) were significant predictors of hsCRP levels. These findings suggest that hsCRP levels should be adjusted for BMI, ethnicity, education level, disease activity and medications when conducting cardiovascular risk assessment in patients with lupus.
Lupus 2008 Feb
PMID:Predictors of high sensitivity C-reactive protein levels in patients with systemic lupus erythematosus. 1825 Jan 34

The accelerated development of atherosclerosis with increased risk of cardiovascular disease in systemic lupus erythematosus (SLE) patients is not well understood. An appropriate mouse model would greatly help to understand the mechanisms of this association. We have therefore combined the ApoE(-/-) model of atherosclerosis with three different murine models of SLE. We found that induction of cGVH in B6.ApoE(-/-) mice, breeding a Fas null gene onto the B6.ApoE(-/-) mice, and breeding the ApoE(-/-) defect onto MRL/lpr mice all caused a modest increase of atherosclerosis at 24 weeks of age compared to B6.ApoE(-/-) controls. B cells in B6.ApoE(-/-) mice had certain phenotypic differences compared to congenic C57BL/6 mice, as indicated by high expression of MHC II, Fas, CD86, and by increased number of cells bearing marginal zone phenotype. Furthermore, B6ApoE(-/-) mice had significant titers of anti-oxLDL and anti-cardiolipin autoantibodies compared to their B6 counterparts. Our studies also indicate that, following induction of cGVH, marginal zone B cells in B6.ApoE(-/-) are depleted, and there is considerable increase in anti-oxLDL and anti-cardiolipin abs along with secretion of lupus-specific autoantibodies, such as anti-dsDNA and anti-chromatin abs. Histological sections showed that cGVH and/or Fas deficiency could exacerbate atherosclerosis. The production of anti-oxLDL and anti-cardiolipin in ApoE(-/-) mice was also increased. These observations define a connection between induction of lupus-like symptoms and development of severe atherosclerosis in ApoE deficient lupus mouse models.
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PMID:Accelerated atherosclerosis in ApoE deficient lupus mouse models. 1832 38

C-reactive protein (CRP) is a heritable acute-phase plasma protein also expressed at low, basal, levels in healthy individuals. Elevated basal CRP has been associated with increased cardiovascular risk, while CRP dysregulation may be a feature of systemic lupus erythematosus (SLE). In this cohort of 496 Caucasian SLE families we estimated basal CRP heritability, h(2)= 27.7%. We typed a dense map of CRP single nucleotide polymorphisms (SNPs) and found that seven were associated with basal CRP using both a regression approach and an orthogonal family-based test (P = 0.001-0.011), as were haplotypes carrying the minor allele of these SNPs. SNPs in the interleukin-1beta and interleukin-6 genes were associated with basal CRP. No association was seen between CRP genotype and SLE. Using a variance components approach we estimated that the CRP genotype accounted for only 15% of the total genetic component of basal CRP variation, perhaps explaining the limited evidence of association between CRP and disease. Most of the genetic determinants of basal CRP variation therefore remain unknown. Multiple genes may be involved and identifying them will provide an insight into pathways regulating CRP expression, highlight potential cardiovascular disease and SLE candidates and improve the ability of basal CRP to predict cardiovascular risk.
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PMID:Quantification of the genetic component of basal C-reactive protein expression in SLE nuclear families. 1837 21

Atherosclerosis is an inflammatory disease characterised by presence of activated immune competent cells in middle-sized and large arteries and is the major cause of cardiovascular disease (CVD). The risk of CVD is very high in systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are, therefore, important clinical problems but may in addition also have implications for the role of immune reactions in CVD in general. Others and we have recently demonstrated that risk factors for CVD in SLE are both traditional and non-traditional acting in concert. Traditional risk factors implicated in SLE include, for example, dyslipidemia (especially high triglycerides), hypertension, renal disease, non-traditional as inflammation, antiphospholipid antibodies (aPL) and low-density lipoprotein (LDL) oxidation are also associated with CVD in SLE. Atherothrombosis is likely to be a major underlying mechanism and is not only an increased risk of thrombosis per se. It is possible that factors like proinflammatory reactions or prothrombotic factors, such as aPL, make atherosclerotic lesions in SLE more prone to rupture than in 'normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients is presently not clear. Treatment of patients with SLE should include a close monitoring of traditional risk factors and also the above-mentioned non-traditional for CVD.
Lupus 2008 May
PMID:Systemic lupus erythematosus and cardiovascular disease. 1849 Apr 8


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