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)

The effect of total-body cold exposure on plasma concentrations of von Willebrand factor (vWF), endothelin-1 (ET) and thrombomodulin (TM), all of which are considered to be generated from the endothelium, was studied in systemic lupus erythematosus (SLE) patients with and without Raynaud's phenomenon. The plasma levels of vWF, ET and TM in SLE patients, irrespective of the presence of Raynaud's phenomenon, were significantly higher than in normal controls even before the cold provocation test. After the cold provocation test, plasma levels of vWF and ET were significantly higher in SLE patients with Raynaud's phenomenon than in those without and in normal controls. No significant increase in TM was observed in either the SLE patients or the controls. These results suggest that SLE patients, regardless of the presence of Raynaud's phenomenon, are in a hypercoagulable state and that this state may be further intensified by cold exposure. Hence, it is concluded that we should consider antithrombotic therapy for SLE patients, especially those with Raynaud's phenomenon, to prevent unwanted activation of the coagulation system and possible endothelial damage.
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PMID:Effect of total-body cold exposure on plasma concentrations of von Willebrand factor, endothelin-1 and thrombomodulin in systemic lupus erythematosus patients with or without Raynaud's phenomenon. 133 60

Forty-three patients with systemic scleroderma (SSc), 10 with non-SSc (6 cases of systemic lupus erythematosus and 4 cases of dermatomyositis), 14 cases of mild- or non-sclerotic type of scleroderma with capillaroscopic abnormalities of nailfolds (SSD; scleroderma spectrum disorders) and 10 healthy volunteers (HC) were subjected to examination of plasma levels of endothelin-1 (ET-1). The sex ratios (male/female) in the patients with SSc, non-SSc and HC were 7:36, 4:6 and 0:10, and the ranges of their ages were 22-74, 19-78 and 33-62 years old, respectively. The plasma levels of ET-1 in SSD, SSc (Barnett I;15), SSc (Barnett II;16), SSc (Barnett III;12 cases), non-SSc and HC were 1.67 +/- 0.37 2.04 +/- 0.58 2.04 +/- 0.68 1.85 +/- 041 191 +/- 0.7 and 1.31 +/- 0.34 pg/ml, respectively, confirming previous results from other laboratories. The plasma levels of ET-1 statistically differ between each collagen disease (SSD, SSc and non-SSc) and HC using Student's t-test (P < 0.05). Although a statistically significant difference was obtained in the plasma levels of ET-1 between the SSc group (6 cases) and HC (6 cases) measured at 06:00, 12:00, 18:00 and 24:00 h, there was no significant circadian variation of plasma levels of ET-1 at these times in both the SSc group and HC. The present study revealed that (1) the ET-1 level in HC showed no circadian fluctuation, and remained at a low level (0.8-1.6 pg/ml). (2) When compared to HC, ET-1 in blood plasma of patients with SSc was elevated (0.3-3 pg/ml) throughout the day and night (P < 0.05). (3) ET-1 tended to increase more at midnight (24:00 h) in the SSc group without PSL treatment, though no statistical significance was obtained. (4) TAT showed a significant increase at noon (12:00 h) suggesting coagulation activity in patients with SSc, but PlC did not show a significant increase compared to HC. In conclusion, the observed increase of vasoconstrictive ET-1 in the patients with SSc throughout the day and night may make maintenance of peripheral blood flow more difficult, may have some biological origin and should be further investigated.
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PMID:Is there circadian variation of plasma endothelin (ET-1) in patients with systemic scleroderma (SSc)? 943 6

Endothelial cell functions, primarily involving regulated mediator secretion or altered surface protein expression, are vital for normal homeostasis. Endothelial cells secrete the potent vasodilator and anti-platelet agent prostacyclin and nitric oxide, and also the potent vasoconstrictor peptide endothelin-1; they control the selective adhesion and emigration of leukocytes from the bloodstream; and they are the source of circulating von Willebrand factor, tissue plasminogen activator and type 1 plasminogen activator inhibitor. The properties of healthy endothelium ensure that an antithrombotic and anticoagulant balance is maintained in the bloodstream, and provide a tonic vasodilator action that controls blood flow and pressure on a minute-to-minute basis. Disturbances of normal endothelial function are strongly implicated in the pathogenesis of atherosclerosis and autoimmune vasculitic diseases including lupus.
Lupus 2000
PMID:Normal endothelial cell function. 1080 85

The pathogenesis of antiphospholipid antibody (aPL) related thrombosis is multifactorial and includes, amongst others, enhanced coagulation activation measured as prothrombin fragment 1 + 2 (F1 + 2), elevated plasma levels of von Willebrand factor (vWF), plasminogen activator inhibitor (PAI) and endothelin-1 (ET-1) as well as heightened thromboxane generation and lipid peroxidation. To evaluate the antioxidant susceptibility of some of the above pathways, probucol (500 mg/d orally, a cholesterol lowering agent bearing antioxidant properties) was administered for a three week period to 14 subjects with aPL and to seven healthy controls. At baseline aPL participants showed higher plasma levels of vWF (P = 0.006), ET-1 (P = 0.0002) and enhanced urinary excretion of 11-dehydro-thromboxane-B2 (TXB2) (P = 0.0004), F2-isoprostanes (marker of lipid peroxidation) (P = 0.02) and albumin (P = 0.04) than controls. In the aPL group baseline IgG anticardiolipin (aCL) titre positively related with urinary TXB2 (r2 = 0.43, P = 0.01) and inversely with urinary NOx (r2 = -0.6, P = 0.005) whereas urinary NOx and TXB2 were negatively correlated (r2 = -0.42, P = 0.01). After the treatment period significant decreases from baseline values were noted for PAI (P = 0.01), ET-1 (P = 0.006), TXB2 (P = 0.02), F2-isoprostanes (P = 0.01) and albuminuria (P = 0.01) in aPL participants but not in controls. These pilot data support oxidative sensitive mechanisms and a potential role for antioxidant treatment in the pathogenesis of aPL induced vasculopathy.
Lupus 2000
PMID:Antioxidant susceptibility of pathogenic pathways in subjects with antiphospholipid antibodies: a pilot study. 1119 24

Diabetic retinopathy (DR) is a major cause of blindness in the working population of the Western world and there is no doubt that its prevalence is strongly related to the duration of diabetes and the glycemic control. However, although intensive diabetes management, with the goal of achieving near-normal glycemia, has been shown to prevent and/or delay the onset of DR, there is now ample of evidence that the development of this microangiopathy is a multifactorial process in which genetic, metabolic, haemostatic and growth factors play an important role. Moreover, given the suggestions that immunological mechanisms might have a role in the pathogenesis of diabetic microangiopathy via immune complex deposition, it has been hypothesized that antiphospholipid antibodies (A-Ab) directed against endothelial antigens could be responsible for initiating vascular injury. In particular, not only A-Ab production was found to be increased in patients with overt nephropathy or macroangiopathy but also Lupus Anticoagulant positivity, representing an intersection point between immune and haemostatic alterations, has been highlighted as a potential and additional risk factor in the pathogenesis of microangiopathy in type 1 diabetics. Moreover, given the high levels of activated protein C, endothelin-1 and thrombo-modulin that have been observed in normo-albuminuric and uncomplicated patients, it has been concluded that the vascular endothelium shifts pathologically from an antithrombotic to a prothrombotic state even in the early phases of the disease. This condition was found to be more pronounced in subjects with anticardiolipin positivity and/or high circulating immune complexes concentrations, since they possess the ability not only to induce platelet activation and aggregation but also to activate the complement system via the classical pathway. Therefore, a potential synergism between generation of autoantibodies, haemostatic alterations and endothelial stress has been suggested, a stimulating hypothesis that needs further studies to be clarified in its complexity.
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PMID:Are phospholipid-binding antibodies implicated in the pathogenesis of diabetic microangiopathy? 1523 81

Systemic vasculitis, an inflammatory necrotizing disease of the blood vessel walls, can occur secondary to autoimmune diseases, including connective tissue diseases. Various pathogenic mechanisms have been implicated in the induction of vasculitis, including cell-mediated inflammation, immune complex-mediated inflammation and autoantibody-mediated inflammation. This inflammatory activity is believed to contribute to accelerated atherosclerosis, and also leads to increased risk for cardiovascular events in patients with rheumatoid arthritis and systemic lupus erythematosus. Endothelial cell activation is a common pathogenic pathway in the systemic vasculitis associated with rheumatoid arthritis and systemic lupus erythematosus, with elevated levels of endothelin-1 potentially inducing vascular dysregulation.
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PMID:Vasculitis: mechanisms involved and clinical manifestations. 1776 47

The aim of this study was to evaluate traditional risk factors for coronary artery disease (CAD), homocysteine, anti-oxidized low-density lipoprotein (anti-oxLDL), anti-lipoprotein lipase (anti-LPL) and endothelin-1 (ET-1) in patients with primary anti-phospholipid syndrome (APS), furthermore verify possible association among these variables and arterial thrombosis. Thirty-eight women with primary APS and 30 age-and-sex-matched controls were evaluated. Patients presented higher-LDL and triglycerides levels and lower-HDL levels than controls. Anti-LPL antibodies were not detected in both groups. The mean number of risk factors was higher in patients than in controls (P = 0.030). Anti-oxLDL antibodies, homocysteine and ET-1 mean levels were similar between groups, but abnormal homocysteine levels were found only among primary APS patients (P = 0.031). Hypertension and the presence of at least one risk factor for CAD were more prevalent in patients with arterial involvement than those without. Homocysteine levels and mean number of risk factors for CAD were significantly higher in patients with arterial thrombosis than controls. In a multivariate analysis hypertension was the only independently associated with arterial thrombosis (OR 14.8, 95% CI = 2.1-100.0, P = 0.006). This study showed that in primary APS patients other risk factors besides anti-phospholipid antibodies contribute for the occurrence of arterial events and the most important factor was hypertension.
Lupus 2007
PMID:Impact of hypertension and hyperhomocysteinemia on arterial thrombosis in primary antiphospholipid syndrome. 1789

The need of blood flow to different organs varies rapidly over time which is why there is sophisticated local regulation of blood flow. The term dysregulation simply means that blood flow is not properly adapted to this need. Dysregulative mechanisms can lead to an over- or underperfusion. A steady overperfusion may be less critical for long-term damage. A constant underperfusion, however, can lead to some tissue atrophy or in extreme situations to infarction. Unstable perfusion (underperfusion followed by reperfusion) leads to oxidative stress. There are a number of causes that lead to local or systemic vascular dysregulation. Systemic dysregulation can be primary or secondary of nature. A secondary dysregulation is due to other autoimmune diseases such as rheumatoid arthritis, giant cell arteritis, systemic lupus erythematodes, multiple sclerosis, colitis ulcerosa, or Crohns disease. Patients with a secondary vascular dysregulation normally have a high level of circulating endothelin-1 (ET-1). This increased level of ET-1 leads to a reduction of blood flow both in the choroid and the optic nerve head but has little influence on autoregulation. In contrast, primary vascular dysregulation has little influence on baseline ocular blood flow but interferes with autoregulation. This, in turn, leads to unstable oxygen supply, which seems to be a relevant component in the pathogenesis of glaucomatous optic neuropathy.
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PMID:What is the link between vascular dysregulation and glaucoma? 1799 40

Interstitial cells, inflammatory-immune cells, tubular cells and endothelial cells of the peritubular capillaries have arisen as possible major players of the nephron damage in lupus nephritis. Increased ICAM-1, Von Willebrand factor, soluble endothelial protein C receptors and decreased ADAMS-13 point to a diffuse vascular damage. Albuminuria elicits a rapid generation of hydrogen peroxide in proximal tubular cells along with nuclear factor-kB activation, endothelin-1 and transforming growth factor (TGF-beta1) upregulation. TGF-beta1 enhances epithelial-to-mesenchymal transdifferentiation. Albuminuria also enhances the expression of macrophage chemotactic protein-1 and macrophage inflammatory protein-1alpha, thus leading to increased interstitial inflammation. TGF-beta1 and thrombospondin-1, a putative activator of TGF-beta, induce apoptosis of peritubular capillaries, as well as of glomerular endothelial cells. All these events can be counteracted by hepatocyte growth factor (HGF), which is expressed by the epithelial tubular cells and stimulates the growth of epithelial cells (mitogen), enhances the motility of epithelial cells (motogen), induces renal epithelial tubule regeneration (morphogen) and enhances angiogenesis (angiogen). The balance between TGF-beta1 and HGF could be a key to define the prognostic value of kidney histopathology at baseline and during follow-up, in lupus nephritis. Therapeutic strategies aiming at altering the biological balance in the patients are at hand to test and prove the experimental evidences.
Lupus 2008 Jun
PMID:Renal interstitial cells, proteinuria and progression of lupus nephritis: new frontiers for old factors. 1853 6

The aim of the study was to evaluate the correlation between selected serum endothelial cell activation markers such as vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble thrombomodulin (sTM), soluble E-selectin (sE-selectin), disease activity, and microvascular changes determined by nailfold capillaroscopy in patients with systemic lupus erythematosus (SLE). Serum levels of VEGF, ET-1, sTM, and sE-selectin were determined by an enzyme-linked immunosorbent assay in 80 SLE patients. The disease activity was measured with Systemic Lupus Erythematosus Disease Activity Index score. Nailfold capillaroscopy was performed in all patients. Positive correlation was found between VEGF and both ET-1 (r = 0.294, p < 0.01) and sE-selectin (r = 0.274, p < 0.05) serum levels as well as between sTM and ET-1 (r = 0.273, p < 0.05) serum concentrations. We noticed also positive correlation between VEGF (r = 0.224, p < 0.05) and ET-1 (r = 0.471, p < 0.001) serum levels and disease activity, and also between VEGF serum concentration and grade of morphological changes observed by nailfold capillaroscopy (r = 0.458, p < 0.001). There was also positive correlation between capillaroscopic score and disease activity (r = 0.339, p < 0.01). Our data suggest that correlation between VEGF and both ET-1 and E-selectin serum levels as well as between sTM and ET-1 serum concentrations may reflect their participation in the pathogenesis of SLE. VEGF seems to reflect changes in microcirculation in the course of SLE, visualised by nailfold capillaroscopy. The relationship between changes in nailfold capillaroscopy, endothelial cell activation markers, and the clinical activity of SLE points to an important role of microvascular abnormalities in the clinical manifestation of the disease.
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PMID:Analysis of correlations between selected endothelial cell activation markers, disease activity, and nailfold capillaroscopy microvascular changes in systemic lupus erythematosus patients. 1990 14


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