Plasma levels of active Von Willebrand factor are increased in patients with first ST-segment elevation myocardial infarction: A multicenter and multiethnic study

Rutten, Bart P. F.; Maseri, Attilio; Cianflone, Domenico; Laricchia, Alessandra; Cristell, N.; Durante, Alessandro; Spartera, Marco; Ancona, Francesco; Limite, Luca Rosario; Hu, Dayi; Li, H; Uren, NG; Groot, PG de; Pm, Mannucci; Roest, Mark

doi:10.1177/2048872614534388

Cited by 52 publications

(48 citation statements)

References 39 publications

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“…The increase in VWF observed in our assay may mirror the in vivo effects seen in some of APS patients as they tend to have elevated levels of total and active VWF . Elevations of VWF in turn can lead to thrombotic events . Interestingly, the variation of VWF release induced by anti‐β2GPI antibodies from different patients suggests that elevations of VWF are not the sole driver of the prothrombotic state of APS and is consistent with the “multi‐factorial” activation hypothesis of APS.…”

Section: Discussionsupporting

confidence: 73%

“…While deficiency of VWF characterizes von Willebrand disease, elevations of VWF have also been implicated in thrombotic disorders, specifically cardiovascular disease, myocardial infarction, and arterial ischemic stroke. [12][13][14][15] The unique predisposition of APS to arterial stroke suggests that VWF, which has significant importance in arterial, platelet-rich thrombi, may play a role in the predisposition to thromboembolism seen in APS. Several reports have demonstrated an increase in cell surface VWF on endothelial cells treated with APL-Abs and higher levels of active VWF in the serum of patients with anti-β2GPI antibodies.…”

Section: Introductionmentioning

confidence: 99%

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Effects of anti‐β2GPI antibodies on VWF release from human umbilical vein endothelial cells and ADAMTS13 activity

McCrae

Ashworth

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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Essentials The antiphospholipid syndrome predisposes to thrombosis due to activation of endothelium and blood components.The role of anti‐β2GPI antibodies in VWF release and ADAMTS13 function is not well understood.Some anti‐β2GPI antibodies induce endothelial release of soluble VWF but not VWF strings.An anti‐β2GPI antibody can decrease ADAMTS13 activity in vitro similar to ex vivo results. BackgroundAntiphospholipid syndrome (APS) is characterized by recurrent thromboembolic events in the setting of pathologic autoantibodies, some of which are directed to β2‐Glycoprotein 1 (β2GPI). The mechanisms of thrombosis in APS appear to be multifactorial and likely include a component of endothelial activation. Among other things, activated endothelium secretes von Willebrand factor, a hemostatic protein that in excess can increase the risk of thrombosis.ObjectiveWe hypothesized that anti‐β2GPI antibodies could regulate the release and modulation of VWF from endothelial cells.Patients/MethodsIsolated anti‐β2GPI antibodies from patients with APS were assayed for their ability to induced VWF release from HUVECs and modulate the effects of ADAMTS13 in a shear‐dependent assay.ResultsWe observed that anti‐β2GPI antibodies from some patients with APS induced VWF release from human endothelial cells but did not induce formation of cell‐anchored VWF‐platelet strings. Finally, we also determined that one of the Anti‐β2GPI antibodies tested can inhibit the function of ADAMTS13, the main modulator of extracellular VWF.ConclusionsThese results suggest that VWF and ADAMTS13 may play a role in the prothrombotic phenotype of APS.

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Effects of anti‐β2GPI antibodies on VWF release from human umbilical vein endothelial cells and ADAMTS13 activity

McCrae

Ashworth

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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“…A recent multicenter and multiethnic study (China, Italy and Scotland) found that plasma levels of active VWF are an independent risk factor for first STEMI in patients, and confirm the presence of VWF abnormalities in patients with STEMI [55]. Consistent with such studies, the prevalence of cardiovascular diseases (CVD) in VWD patients is around half the prevalence of CVD in non-VWD patients [56].…”

Section: Vwf In Diseases Beyond Vwd and Ttpmentioning

confidence: 70%

Regulation of VWF expression, and secretion in health and disease

Xiang

Hwa

2016

Current Opinion in Hematology

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PURPOSE OF REVIEW VWF is a large multi-domain, multimeric glycoprotein that plays an essential role in regulating the balance between blood clotting and bleeding. Aberrant VWF regulation can lead to a spectrum of diseases extending from bleeding disorders (VWD) to aberrant thrombosis (TTP). Understanding the biology of VWF expression and secretion is essential for developing novel targeted therapies for VWF related hemostasis disorders. RECENT FINDINGS A number of recent elegant in vitro and in vivo studies will be highlighted including the discovery of intronic splicing in the VWF gene, miRNA regulated VWF gene expression, and syntaxin binding protein and autophagy mediated VWF secretion. Compared with the already established critical role of VWF in VWD and TTP pathophysiology, additional clinical studies have clarified and reinforced the association of increased plasma levels of VWF with an increased risk of stroke, myocardial infarction, venous thrombosis and diabetic thrombotic complications. Moreover, experimental mouse models of ischaemic stroke and myocardial infarction have further support VWF as a potential therapeutic target. SUMMARY VWF biosynthesis, maturation, and secretion is a complex process, which mandates tight regulation. Significant progress has been made in our understandings of VWF expression and secretion and its association with thrombotic diseases, contributing to the development of novel targeting VWF drugs for prevention and treatment of deficient and enhanced hemostasis.

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“…More recently, in the ATHEROREMO-IVUS study [81], in patients with stable CAD (SCAD), an increased level of VWF:Ag was associated with higher coronary plaque burden, adverse CV outcome, and death during 1-year of follow-up. VWF is also an independent risk factor for first STEMI: levels of VWF are significantly increased in patients with first ST-elevation myocardial infarction (STEMI) rather than in controls [82]. Finally, Marcucci et al reported a possible relation between lower levels of ADAMTS13 and higher residual platelet reactivity (RPR), a marker of resistance to antiplatelet therapy associated with increased risk of ischemic events [83].…”

Section: Vwf In Metabolic and Cardiovascular Disease: Animal Modelmentioning

confidence: 99%

The Role of von Willebrand Factor in Vascular Inflammation: From Pathogenesis to Targeted Therapy

Gragnano

Sperlongano

Golia

et al. 2017

Mediators of Inflammation

174

162

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Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions. Moreover, VWF and ADAMTS13 have been recently proposed as prognostic biomarkers in cardiovascular, metabolic, and inflammatory diseases, such as diabetes, stroke, myocardial infarction, and sepsis. All these features make VWF an attractive therapeutic target in thromboinflammation. Several lines of research have recently investigated “tailor-made” inhibitors of VWF. Results from animal models and clinical studies support the potent anti-inflammatory and antithrombotic effect of VWF antagonism, providing reassuring data on its safety profile. This review describes the role of VWF in vascular inflammation “from bench to bedside” and provides an updated overview of the drugs that can directly interfere with the VWF/ADAMTS13 axis.

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Plasma levels of active Von Willebrand factor are increased in patients with first ST-segment elevation myocardial infarction: A multicenter and multiethnic study

Abstract: We found evidence that plasma levels of active VWF are an independent risk factor for first STEMI in patients from three different ethnic groups. Our findings confirm the presence of VWF abnormalities in patients with STEMI and may be used to develop new therapeutic approaches.

Cited by 52 publications

References 39 publications

Effects of anti‐β2GPI antibodies on VWF release from human umbilical vein endothelial cells and ADAMTS13 activity

Effects of anti‐β2GPI antibodies on VWF release from human umbilical vein endothelial cells and ADAMTS13 activity

Regulation of VWF expression, and secretion in health and disease

The Role of von Willebrand Factor in Vascular Inflammation: From Pathogenesis to Targeted Therapy

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