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Inhibition of nitric oxide and antiphospholipid antibody-mediated thrombosis.

ABSTRACT: The antiphospholipid syndrome (APS) is characterized by recurrent vascular thrombosis, thrombocytopenia, and fetal loss occurring in the presence of antiphospholipid antibodies (aPL). Along with arterial and venous thrombosis and pregnancy complications, patients with APS have an increased risk of myocardial infarction, stroke, and coronary artery disease, resulting from vascular cell dysfunction induced by aPL. Accumulating evidence to date indicates that interactions between circulating aPL and cell surface molecules of target cells, primarily endothelial cells and platelets, underlie the vascular disease phenotypes of APS. However, the molecular basis of APS is poorly understood. Nitric oxide produced by endothelial cells is a key determinant of vascular health that regulates several physiologic processes, including thrombosis, endothelial-leukocyte interaction, vascular cell migration, and the modulation of vascular tone. This review will discuss recent findings that indicate a novel mechanism by which aPL antagonize endothelial cell production of nitric oxide and thereby promote thrombosis.

SUBMITTER: Mineo C

PROVIDER: S-EPMC3625922 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Inhibition of nitric oxide and antiphospholipid antibody-mediated thrombosis.

Mineo Chieko C

Current rheumatology reports 20130501 5

The antiphospholipid syndrome (APS) is characterized by recurrent vascular thrombosis, thrombocytopenia, and fetal loss occurring in the presence of antiphospholipid antibodies (aPL). Along with arterial and venous thrombosis and pregnancy complications, patients with APS have an increased risk of myocardial infarction, stroke, and coronary artery disease, resulting from vascular cell dysfunction induced by aPL. Accumulating evidence to date indicates that interactions between circulating aPL an ...[more]

PMID: 23519891

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Project description:Q fever is a neglected and potentially fatal disease. During acute Q fever, antiphospholipid antibodies are very prevalent and have been associated with fever, thrombocytopenia, acquired heart valve disease, and progression to chronic endocarditis. However, thrombosis, the main clinical criterion of the 2006 updated classification of the antiphospholipid syndrome, has not been assessed in this context. To test whether thrombosis is associated with antiphospholipid antibodies and whether the criteria for antiphospholipid syndrome can be met in patients with acute Q fever, we conducted a cross-sectional study at the French National Referral Center for Q fever.Patients included were diagnosed with acute Q fever in our Center between January 2007 and December 2015. Each patient's history and clinical characteristics were recorded with a standardized questionnaire. Predictive factors associated with thrombosis were assessed using a rare events logistic regression model. IgG anticardiolipin antibodies (IgG aCL) assessed by an enzyme-linked immunosorbent assay were tested on the Q fever diagnostic serum. A dose-dependent relationship between IgG aCL levels and thrombosis was tested using a receiver operating characteristic (ROC) analysis.Of the 664 patients identified for inclusion in the study, 313 (47.1%) had positive IgG aCL and 13 (1.9%) were diagnosed with thrombosis. Three patients fulfilled the antiphospholipid syndrome criteria. After multiple adjustments, only positive IgG aCL (relative risk, 14.46 [1.85-113.14], P = .011) were independently associated with thrombosis. ROC analysis identified a dose-dependent relationship between IgG aCL levels and occurrence of thrombosis (area under curve, 0.83, 95%CI [0.73-0.93], P < .001).During acute Q fever, antiphospholipid antibodies are associated with thrombosis, thrombocytopenia, and acquired valvular heart disease. Antiphospholipid antibodies should be systematically assessed in acute Q fever patients. Hydroxychloroquine, which has been previously shown to antagonize IgG aCL pathogenic properties, should be tested in acute Q fever patients with anticardiolipin antibodies to prevent antiphospholipid-associated complications.Key Point: In addition to fever, thrombocytopenia and acquired valvular heart disease, antiphospholipid antibodies are associated with thrombosis during acute Q fever.

Dataset Information

Inhibition of nitric oxide and antiphospholipid antibody-mediated thrombosis.

Publications

Inhibition of nitric oxide and antiphospholipid antibody-mediated thrombosis.

Similar Datasets

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