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)

Women with systemic lupus erythematosus (SLE) are at risk for premature atherothrombosis independent of Framingham risk factors. We investigated whether endothelial cell (EC) apoptosis predicts abnormal vasomotor tone and contributes to circulating tissue factor (TF) levels in this disease. Brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation were determined in women with SLE, healthy control subjects, and subjects with coronary artery disease (CAD) (n = 43/group). Quantification of circulating apoptotic ECs was performed by flow cytometry (CD146(+) cells that stained for Annexin V [CD146(AnnV+)]) and immunofluorescent microscopy. Plasma TF was measured by enzyme-linked immunosorbent assay (ELISA). Compared with healthy control and CAD subjects, patients with SLE had higher numbers of circulating CD146(AnnV+) cells (10 +/- 3, 18 +/- 5, and 89 +/- 32 cells/mL, respectively, mean +/- SEM; P <.01). Increased CD146(AnnV+) cells correlated strongly with abnormal vascular function (P =.037). After adjusting for known predictors of endothelial function, CD146(AnnV+) was the only variable that predicted FMD (beta = -4.5, P <.001). Increased CD146(AnnV+) was strongly associated with elevated levels of circulating TF (r =.46, P =.002). Circulating apoptotic ECs are elevated in young women with SLE and strongly correlate with markedly abnormal vascular function and elevated TF levels. Heightened endothelial apoptosis may represent an important mechanism for development of atherothrombosis in SLE.
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PMID:Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity. 1472 73

From time to time there have been reports of autoimmune disease succumbing to tetracycline antibiotics, but many have assumed this was due to coincidence, or to some ill-defined 'anti-inflammatory property' of the tetracyclines. But now the inflammation of sarcoidosis has succumbed to antibiotics in two independent studies. This review examines the cell wall deficient (antibiotic resistant) bacteria which have been found in tissue from patients with sarcoidosis. It examines how such bacteria can infect the phagocytes of the immune system, and how they may therefore be responsible for not only sarcoid inflammation, but also for other autoimmune disease. Proof positive of a bacterial pathogenesis for Sarcoidosis includes not only the demonstrated ability of these studies to put the disease into remission, but also the severity of Jarisch-Herxheimer shock resulting from endotoxin release as the microbes are killed. Studies delineating the hormone responsible for phagocyte differentiation in the Th1 immune response, 1,25-dihydroxyvitamin D, are discussed, and its utility as a marker of Th1 immune inflammation is reviewed. Finally, data showing that the behavior of this hormone is also aberrant in rheumatoid arthritis, systemic lupus erythematosus, and Parkinson's, raise the possibility that these diseases may also have a CWD bacterial pathogenesis.
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PMID:Sarcoidosis succumbs to antibiotics--implications for autoimmune disease. 1524 25

Our objective was to compare brachial artery endothelium dependent and independent vasodilation in lupus patients and healthy females, by means of high-resolution noninvasive brachial artery ultrasound. Endothelially mediated vasodilation was estimated noninvasively by examination of brachial artery responses to postischemic reactive hyperemia and endothelial independent vasodilation from response to sublingual glycerlynitrate (GTN) using high-resolution external vascular ultrasound. Five patients with known coronary artery disease (CAD), five with subclinical CAD, five with no CAD and five control subjects were assessed. Endothelium dependent vasodilation was significantly blunted in lupus patients with CAD as compared with healthy female controls (0.11 versus 11.1%, P = 0.018). Corresponding values for lupus patients with subclinical CAD and no CAD were 11 and 9.6%, respectively. For each subject, endothelium dependent vasodilation (EDV) was related to endothelium independent vasodilation (EIV) to adjust for varying vascular smooth muscle responses to GTN in individual subjects. This ratio was markedly depressed in lupus patients with CAD as compared with control subjects (0.12 versus 1.15). The corresponding EDV/EIV ratios for patients with subclinical CAD and no CAD were similar at 0.69 and 0.65, respectively. The conclusion was that flow mediated vasodilation in lupus patients with coronary artery disease is markedly depressed as compared to healthy subjects.
Lupus 2004
PMID:Impaired brachial artery endothelium dependent flow mediated dilation in systemic lupus erythematosus: preliminary observations. 1546 88

Endothelial function, measured noninvasively by brachial artery flow-mediated dilatation (FMD), has been shown to be impaired in patients with systemic lupus erythematosus (SLE). We hypothesized that depressed FMD in SLE patients is associated with increased levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis and regulator of vasoactivity. In this cross-sectional study of female SLE patients under the age of 55, putative markers of cardiovascular disease (CVD) such as PAI-1 were measured in addition to lupus-related disease activity (SLEDAI). The primary outcome, FMD, was measured using high-resolution ultrasound of the brachial artery gated to the R wave to determine endothelial-dependent vasomotion. Endothelial-independent vasomotion was measured in response to nitroglycerin (NMD). Seventy-six female SLE patients, mean age 38.3 +/- 9.4 years, were included. All patients demonstrated normal NMD responses, indicating that depression of FMD was related to decreased endothelial nitric oxide production. Increased PAI-1 was related to depressed FMD by univariate regression (P = 0.004). In a multivariable regression model adjusting for t-PA (tissue plasminogen activator)/PAI-1 ratio, SLEDAI, age at visit, family history of cardiovascular disease, SLE disease duration and body mass index, every 1 ng/mL increase in PAI-1 was associated with a reduction of 0.07 units FMD (P = 0.039). PAI-1 was associated with impaired endothelial dysfunction, after controlling for several potential confounders. Given the high incidence of cardiovascular disease in SLE, further investigation of the role of subclinical markers of CVD is needed.
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PMID:Plasminogen activator inhibitor-1 is associated with impaired endothelial function in women with systemic lupus erythematosus. 1612 68

The utility of flow mediated dilation (FMD) a measure of endothelial function is limited by operator dependence. Pulse amplitude tonometry (PAT) is a novel, less operator-dependent technique to assess endothelial function. This study compares PAT to FMD in SLE and controls. Thirty women with SLE and 31 controls were enrolled. Medications, cardiovascular disease and risk factors, SLE activity (SLAM-R) and damage (SLICC-DI) were recorded. FMD and PAT were performed simultaneously. Endothelium-independent function was assessed with nitroglycerin. Average age was 48.3 +/- 10.1 years, SLE duration 16.2 years, SLAM-R 8.3 and SLICC-DI 1.0. Framingham Risk Scores were < or =2% in most subjects. There were no differences between SLE cases and controls in FMD, PAT or response to nitroglycerin. This study found no association between FMD and PAT in SLE or controls. In the 17 SLE cases with a history of Raynaud's, correlation between FMD and PAT was 0.50 (P = 0.04). There was no difference in endothelial function assessed by FMD or PAT in SLE cases versus controls. FMD did not correlate with PAT except in SLE cases with a history of Raynaud's. Correlation between FMD and PAT may be stronger in populations with greater variation in endothelial function and more cardiovascular risk factors.
Lupus 2009 Mar
PMID:A controlled comparison of brachial artery flow mediated dilation (FMD) and digital pulse amplitude tonometry (PAT) in the assessment of endothelial function in systemic lupus erythematosus. 1921 62

Atherosclerosis has a high prevalence in systemic lupus erythematosus (SLE) patients and vascular endothelial dysfunction is the earliest stage of atherosclerosis. The aim of this study was to evaluate the prevalence of vascular endothelial dysfunction and its risk factors in SLE patients and to identify its correlation with disease activity, duration and concomitant conditions in these patients. A total of 84 female SLE patients and 18 healthy young women were included. The vascular endothelial function was evaluated via ultrasonographic assessment of the brachial artery diameter to determine flow-mediated dilation (FMD) and post-TNG dilation-FMD gap (PFG) indexes. FMD indexes of one standard deviation lower than mean FMD of the control group were considered as impaired, and PFG indexes of one standard deviation more than mean PFG of the control group were defined as impaired. SLE patients had a higher prevalence of impaired FMD than healthy subjects (48.8 vs. 5.5%). The prevalence of impaired PFG in SLE cases and healthy subjects was 25 and 5.5%, respectively. FMD and PFG impairment did not have any significant correlation with disease activity, duration, presence of anti-dsDNA, anticardiolipin antibodies, antiphospholipid syndrome and history of receiving cyclophosphamide pulses. Vascular endothelial dysfunction is very common in SLE patients and no single specific factor can explain this finding. We recommend the application of brachial artery Doppler ultrasound as a screening test for detection of early stages of atherosclerosis in SLE patients.
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PMID:Endothelial dysfunction in Iranian lupus patients. 1985 75

DHEA (dehydroepiandrosterone) is a weak androgen with proposed efficacy in the treatment of mild to moderate lupus, and possible beneficial effects on cardiovascular risk and bone mineral density. We hypothesized that treatment with 200 mg a day of Prasterone (DHEA) would improve pre-clinical measures of atherosclerosis: flow-mediated dilatation (FMD), nitroglycerin-mediated dilatation (NMD), and circulating apoptotic endothelial cells (CD 146(AnnV +)), as well markers of bone metabolism. Thirteen premenopausal female patients with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) <or=8 were enrolled in a double-blind placebo-controlled crossover trial for 22 weeks with a 6-week washout between treatment periods. Results reveal high-density lipoprotein (HDL) levels significantly decreased with Prasterone (48.5 versus 56.3 with placebo, p <or= 0.001), and there was a trend towards impairment of endothelial function with Prasterone (brachial artery FMD 3.4% versus 4.4% with placebo, mean difference -1.07, NMD 19.5% versus 24.4% with placebo, mean difference -4.9, p = NS). There were no differences between groups in SLEDAI, CD146( AnnV+) cells, or receptor activator for nuclear factor kB ligand (RANKL)/osteoprotegerin, although RANKL was higher after treatment with Prasterone (mean difference -29.5 units; p = 0.097). This pilot study does not support the use of Prasterone in mild lupus for prevention of atherosclerosis or osteoporosis, and confirms other findings of potentially harmful effects on lipids.
Lupus 2010 Sep
PMID:Effects of prasterone (dehydroepiandrosterone) on markers of cardiovascular risk and bone turnover in premenopausal women with systemic lupus erythematosus: a pilot study. 2053 May 22

Systemic sclerosis (SSc) is a chronic disease of unknown etiology. The main feature of SSc is microvascular disease, but contemporary studies in the field have confirmed the presence of macrovascular affectation. Due to its inflammatory background, and higher cardio- and cerebrovascular death rates, it is presumed that SSc is more frequently associated to accelerated atherosclerosis, similarly to other autoimmune diseases, such as systemic lupus erythematosus or rheumatoid arthritis. The assessment of subclinical atherosclerosis in patients with SSc through different methods (such as intima media thickness, echo-tracking, wave intensity, pulse wave velocity, flow mediated dilation, nitroglycerin mediated dilation, ankle brachial pressure index or coronary angiotomography) has failed to show concordant results, regardless of the used tool. In this review, we try to synthetise the most recent evidence about atherosclerotic involvement in SSc, reviewing the association between SSc and risk factors and also performing a summary of studies that compared atherosclerosis in SSc to controls. Our research leads to the conclusion that in order to elucidate the extent of atherosclerosis and its consequences in SSc, further investigations are needed, combining atherosclerosis assessment tools and larger number of patients.
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PMID:Atherosclerosis in Systemic Sclerosis: a Modern Controversy. 2826 62

Chronic, excessive alcohol use alters brain gene expression patterns, which could be important for initiating, maintaining, or progressing the addicted state. It has been proposed that pharmaceuticals with opposing effects on gene expression could treat alcohol use disorder (AUD). Computational strategies comparing gene expression signatures of disease to those of pharmaceuticals show promise for nominating novel treatments. We reasoned that it may be sufficient for a treatment to target the biological pathway rather than lists of individual genes perturbed by AUD. We analyzed published and unpublished transcriptomic data using gene set enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways to identify biological pathways disrupted in AUD brain and by compounds in the Library of Network-based Cellular Signatures (LINCS L1000) and Connectivity Map (CMap) databases. Several pathways were consistently disrupted in AUD brain, including an up-regulation of genes within the Complement and Coagulation Cascade, Focal Adhesion, Systemic Lupus Erythematosus, and MAPK signaling, and a down-regulation of genes within the Oxidative Phosphorylation pathway, strengthening evidence for their importance in AUD. Over 200 compounds targeted genes within those pathways in an opposing manner, more than twenty of which have already been shown to affect alcohol consumption, providing confidence in our approach. We created a user-friendly web-interface that researchers can use to identify drugs that target pathways of interest or nominate mechanism of action for drugs. This study demonstrates a unique systems pharmacology approach that can nominate pharmaceuticals that target pathways disrupted in disease states such as AUD and identify compounds that could be repurposed for AUD if sufficient evidence is attained in preclinical studies.
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PMID:A Pathway-Based Genomic Approach to Identify Medications: Application to Alcohol Use Disorder. 3188 99