endothelin-1 and Antiphospholipid-Syndrome

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.

Topics: Adult; Albuminuria; Antibodies, Antiphospholipid; Anticholesteremic Agents; Anticoagulants; Antioxidants; Antiphospholipid Syndrome; Arachidonic Acids; Creatinine; Endothelin-1; Female; Humans; Lipids; Male; Middle Aged; Nitric Oxide; Pilot Projects; Probucol; Prothrombin; Thrombosis; Thromboxane B2; von Willebrand Factor; Warfarin

Topics: Adult; Antiphospholipid Syndrome; Arginine; Chronic Disease; Endothelin-1; Endothelium, Vascular; Female; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Prognosis; Thrombosis; Young Adult

In the article the concentration of endothelin-1 in patients with different variants of APS was analyzed and its relationship with disease course, dyslipidemia, levels of antiphospholipid antibodies and ath rosclerotic vascular lesions was assessed. It was established that high levels of endothelin-1 is a circulating marker of early atherosclerosis, since !it was closely associated'with subclinical manifestations of atherosclerotic vascular lesions, lipid profile. The concentration of endothelin-1 significantly increased with active inflammation and with high levels of antiphospholipid antibodies and does not depend on age, sex, smoking, obesity and physical inactivity.

Topics: Adult; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Atherosclerosis; Biomarkers; Case-Control Studies; Disease Progression; Dyslipidemias; Early Diagnosis; Endothelial Cells; Endothelin-1; Endothelium, Vascular; Female; Humans; Inflammation; Lipid Metabolism; Male; Middle Aged; Motor Activity; Obesity; Smoking

The objective of the study was to investigate the role of endothelin-1 in the pathogenesis of scleroderma renal crisis in patients with systemic sclerosis. We used immunohistochemical analysis with anti-endothelin-1 and anti-von Willebrand factor antibodies in comparing kidney biopsies from patients with systemic sclerosis and scleroderma renal crisis (n = 14); from normal kidneys (n = 5); and from patients with typical hemolytic uremic syndrome and thrombotic microangiopathy (n = 5), antiphospholipid syndrome (n = 6), diabetic nephropathy (n = 5), minimal change disease with cyclosporine toxicity (n = 5), or nephroangiosclerosis (n = 5). Kidney biopsies from all systemic sclerosis patients presented specific lesions: glomerular lesions with thickened capillary walls (n = 6, 42.8%), mesangiolysis (n = 3, 21.4%), fibrin thrombi (n = 3, 21.4%), hypertrophy of juxtaglomerular apparatus (n = 5, 35.7%), arteriolar lesions showing mucinous intimal thickening and lumen mucoid occlusions (n = 13, 92.8%), proliferation of intimal cells (ie, "onion-skin" lesions; n = 13, 92.8%), fibrinoid necrosis (n = 3, 21.4%), and fibrin thrombosis (n = 4, 28.6%). Chronic lesions in large arteries showed modifications such as fibrous intimal thickening (n = 13, 92.8%). The pattern of endothelial staining for endothelin-1 in both glomeruli and arteriolar lesions appears to be specific for scleroderma renal crisis. Glomerular endothelin-1 staining without arteriolar staining was seen in hemolytic uremic syndrome; and isolated arteriolar staining (without glomerular staining) was seen in a number of conditions including antiphospholipid nephropathy, cyclosporine toxicity, and diabetic nephropathy. Endothelin-1 is overexpressed in glomeruli and arterioles of patients with scleroderma renal crisis, which suggests that endothelin-1 might be a therapeutic target in this condition.

Topics: Acute Kidney Injury; Adult; Aged; Antiphospholipid Syndrome; Endothelin-1; Female; Hemolytic-Uremic Syndrome; Humans; Kidney; Male; Middle Aged; Scleroderma, Systemic; von Willebrand Factor

Topics: Antiphospholipid Syndrome; Coronary Vessels; Electrocardiography; Endothelin-1; Female; Humans; Microvascular Angina; Myocardial Infarction; Risk Factors

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.

Topics: Adult; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Autoantibodies; Case-Control Studies; Coronary Artery Disease; Endothelin-1; Female; Homocysteine; Humans; Hyperhomocysteinemia; Hypertension; Lipoprotein Lipase; Lipoproteins, LDL; Middle Aged; Risk Factors; Thrombosis

To explore a possible correlation between endothelin 1 (ET-1), the most potent endothelium-derived contracting factor that modulates vascular smooth muscle tone, and arterial disease in patients with the antiphospholipid syndrome (APS).. Plasma levels of ET-1 were measured in APS patients with (n = 16) and without (n = 11) arterial thrombosis and in non-APS patients with arterial thrombosis (n = 9). In addition, steady-state prepro-ET-1 messenger RNA (mRNA) levels were determined in endothelial cells treated with a range of human monoclonal anticardiolipin antibodies (aCL) (as anti-beta2-glycoprotein I antibodies) by semiquantitative 32P-dCTP-labeled reverse transcription-polymerase chain reaction.. Compared with healthy controls, markedly increased plasma levels of ET-1 were found in APS patients with arterial thrombosis (2.00 +/- 0.87 versus 0.96 +/- 0.37 pg/ml; P = 0.0001) but not in other groups. Three human monoclonal aCL induced prepro-ET-1 mRNA levels significantly more than did control monoclonal antibody lacking aCL activity.. Plasma ET-1 levels correlated significantly with a history of arterial thrombosis in patients with APS. Prepro-ET-1 mRNA was induced by human monoclonal aCL in the in vitro experimental system. The induction of ET-1 by antiphospholipid antibodies might contribute to increased arterial tone, leading to vasospasm and, ultimately, to arterial occlusion.

Topics: Adult; Antibodies, Anticardiolipin; Antibodies, Monoclonal; Antiphospholipid Syndrome; Arterial Occlusive Diseases; beta 2-Glycoprotein I; Cells, Cultured; DNA Primers; Endothelin-1; Endothelins; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins; Humans; Male; Middle Aged; Polymerase Chain Reaction; Protein Precursors; RNA, Messenger; Thrombosis