The effect of platelet activation on the hypercoagulability induced by murine monoclonal antiphospholipid antibodies

Membré, Aurélie; Wahl, Denis; Latger‐Cannard, Véronique; Max, Jean‐Pierre; Lacolley, Patrick; Lecompte, Thomas; Régnault, V.

doi:10.3324/haematol.12364

Cited by 18 publications

(16 citation statements)

References 30 publications

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“…16,17 We recently studied thrombin generation (TG) by calibrated automated thrombography in the diagnosis of LACs 18 and have identified the peak height (PH), the lag time (LT), and their ratio PH/LT to be reliable parameters in the diagnosis of the APS. We have presently further investigated whether TG is suited for the quantitative expression of the LAC activity.…”

Section: Introductionmentioning

confidence: 99%

Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants

Devreese

Peerlinck

Hoylaerts

2010

Blood

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Section: Introductionmentioning

confidence: 99%

Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants

Devreese

Peerlinck

Hoylaerts

2010

Blood

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“…The chromogenic assay measuring the phospholipid-related procoagulant activity (PPA) in VSMCs was performed as described previously for plasma (Wagenvoord et al, 1994 ; Membre et al, 2008 ). VSMCs cultured in 96 well plates were washed and 50 μl of 50 mM Tris, 175 mM NaCl, pH 7.9 (TBS) containing 2 g/l bovine serum albumin (BSA) were added as well as 50 μl of activated factor X (1.2 nM), activated factor V (2.4 nM), CaCl 2 (15 mM) and 50 μl of bovine prothrombin (6 μM) plus Z-Gly-Gly-Arg-AMC substrate (1.25 mM) in 20 mM HEPES pH 7.5 containing 60 g/l BSA.…”

Section: Methodsmentioning

confidence: 99%

Implication of Free Fatty Acids in Thrombin Generation and Fibrinolysis in Vascular Inflammation in Zucker Rats and Evolution with Aging

et al. 2017

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Background: The metabolic syndrome (MetS) and aging are associated with modifications in blood coagulation factors, vascular inflammation, and increased risk of thrombosis.Objectives: Our aim was to determine concomitant changes in thrombin generation in the blood compartment and at the surface of vascular smooth muscle cells (VSMCs) and its interplay with adipokines, free fatty acids (FFA), and metalloproteinases (MMPs) in obese Zucker rats that share features of the human MetS.Methods: Obese and age-matched lean Zucker rats were compared at 25 and 80 weeks of age. Thrombin generation was assessed by calibrated automated thrombography (CAT).Results: Endogenous thrombin potential (ETP) was increased in obese rats independent of platelets and age. Clot half-lysis time was delayed with obesity and age. Interleukin (IL)-1β and IL-13 were increased with obesity and age respectively. Addition of exogenous fibrinogen, leptin, linoleic, or palmitic acid increased thrombin generation in plasma whereas adiponectin had an opposite effect. ETP was increased at the surface of VSMCs from obese rats and addition of exogenous palmitic acid further enhanced ETP values. Gelatinase activity was increased in aorta at both ages in obese rats and MMP-2 activity was increased in VSMCs from obese rats.Conclusions: Our study demonstrated in MetS an early prothrombotic phenotype of the blood compartment reinforced by procoagulant properties of dedifferentiated and inflammatory VSMCs. Mechanisms involved (1) increased fibrinogen and impaired fibrinolysis and (2) increased saturated fatty acids responsible for additive procoagulant effects. Whether specifically targeting this hypercoagulability using direct thrombin inhibitors would improve outcome in MetS is worth investigating.

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“…The supernatant was centrifuged for 4 min at 5000 g to obtain the platelet-poor plasma (PPP). Platelet activation and the generation of cell-derived microparticles in sheared blood samples were evaluated using the chromogenic assay measuring the phospholipid-related procoagulant activity (PPA) as previously described [24].…”

Section: Methodsmentioning

confidence: 99%

Increased Microparticle Production and Impaired Microvascular Endothelial Function in Aldosterone-Salt-Treated Rats: Protective Effects of Polyphenols

et al. 2012

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We aimed to characterize circulating microparticles in association with arterial stiffness, inflammation and endothelial dysfunction in aldosterone-salt-induced hypertension in rats and to investigate the preventive effects of red wine polyphenols. Uninephrectomized male Sprague-Dawley rats were treated with aldosterone-salt (1 µg.h−1), with or without administration of either red wine polyphenols, Provinols™ (20 mg.kg−1.day−1), or spironolactone (30 mg.kg−1.day−1) for 4 weeks. Microparticles, arterial stiffness, nitric oxide (NO) spin trapping, and mesenteric arterial function were measured. Aldosterone-salt rats showed increased microparticle levels, including those originating from platelets, endothelium and erythrocytes. Hypertension resulted in enhanced aortic stiffness accompanied by increased circulating and aortic NO levels and an upregulation of aortic inducible NO-synthase, NFκB, superoxide anions and nitrotyrosine. Flow-induced dilatation was reduced in mesenteric arteries. These effects were prevented by spironolactone. Provinols™ did not reduce arterial stiffness or systolic hypertension but had effects similar to those of spironolactone on endothelial function assessed by flow-mediated vasodilatation, microparticle generation, aortic NO levels and oxidative stress and apoptosis in the vessel wall. Neither the contractile response nor endothelium-dependent relaxation in mesenteric arteries differed between groups. The in vivo effects of Provinols™ were not mediated by mineralocorticoid receptors or changes in shear stress. In conclusion, vascular remodelling and endothelial dysfunction in aldosterone-salt-mediated hypertension are associated with increased circulating microparticles. Polyphenols prevent the enhanced release of microparticles, macrovascular inflammation and oxidative stress, and microvascular endothelial dysfunction independently of blood pressure, shear stress and mineralocorticoid receptor activation in a model of hyperaldosteronism.

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The effect of platelet activation on the hypercoagulability induced by murine monoclonal antiphospholipid antibodies

Abstract: BackgroundTo identify the mechanisms of the hypercoagulability associated with antiphospholipid antibodies, we investigated antibody-mediated platelet activation and interference of antibodies with phospholipid-dependent reactions.

Cited by 18 publications

References 30 publications

Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants

Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants

Implication of Free Fatty Acids in Thrombin Generation and Fibrinolysis in Vascular Inflammation in Zucker Rats and Evolution with Aging

Increased Microparticle Production and Impaired Microvascular Endothelial Function in Aldosterone-Salt-Treated Rats: Protective Effects of Polyphenols

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