Von Willebrand Factor and Cardiovascular Disease: From a Biochemical Marker to an Attractive Therapeutic Target

Gragnano, Felice; Golia, Enrica; Natale, Francesco; Bianchi, Renatomaria; Pariggiano, Ivana; Crisci, Mario; Diana, Vincenzo; Fimiani, Fabio; Limongelli, Giuseppe; Russo, Maria Giovanna; Cirillo, Plinio; Calabrò, Paolo

doi:10.2174/1570161115666170201114835

Cited by 32 publications

(33 citation statements)

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“…21 An imbalance in VWF/ADAMTS-13 axis is also involved in common thrombotic disorders, such as stroke, coronary artery disease, and venous thromboembolism (VTE). 22…”

Section: Vwf Activity Modulation: the Role Of Adamts-13mentioning

confidence: 99%

“…Binding a specific amino acid sequence in the A1-domain, heparin can interfere with VWF-GPIb interaction exerting an antiplatelet effect. 22 In patients with arterial thrombosis, low-molecular-weight heparins showed to, directly and indirectly, antagonize VWF with a positive impact on prognosis. 103 Beyond its anticoagulant activity, this anti-VWF effect may at least partly explain the therapeutic effect of heparin on VTE.…”

Section: Heparinmentioning

confidence: 99%

“…68 Other Drugs N-acetylcysteine, GPIIb/IIIa inhibitors (tirofiban, eptifibatide, and abciximab), and colchicine may also exert anti-VWF effects; however, data on VTE for these drugs are lacking. 22,62,104 The unselective VWF antagonism of routinely used drugs may play a beneficial role in arterial and venous thrombosis. However, this effect is hard to measure in terms of benefit/ risk ratio, and definite conclusions cannot be drawn yet.…”

Section: Heparinmentioning

confidence: 99%

“…To further clarify the potential advantage of the anti-VWF therapy in thrombotic disorders, selective antagonists have been tested in preclinical and clinical studies. 22,[105][106][107][108][109][110][111][112]…”

Section: Heparinmentioning

confidence: 99%

“…Ideally, their antiplatelet and anti-inflammatory effects may potentially exert a protective effect in terms of thrombus formation, endothelial damage, and tissue injury. 22,62 Experimental models recently suggest that the antagonism of the VWF/ADAMTS-13 pathway using specific drugs (including antibodies, nanobodies, and aptamers) could be effective on thrombosis and inflammation without causing serious adverse events. 22 Further studies are needed for clinical approval.…”

Section: Specific Therapiesmentioning

confidence: 99%

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von Willebrand Factor and Venous Thromboembolism: Pathogenic Link and Therapeutic Implications

Calabrò

Gragnano

Golia

et al. 2017

Semin Thromb Hemost

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Venous thromboembolism (VTE) is a frequent cause of disability and mortality worldwide. Von Willebrand factor (VWF) is a major determinant of hemostasis and clot formation, in both arteries and veins. Although VWF is mainly known for its role in arterial thrombosis, several studies suggest a pathogenic role for VWF and its regulator ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in venous thrombosis. Nongenetic and genetic factors, including gene mutations and polymorphisms, aging, hormone status, ABO blood groups, and systemic inflammation, have been involved in the modulation of both VTE predisposition and plasma levels of VWF. In several clinical settings, including inflammatory disease and cancer, VWF and ADAMTS-13 are currently investigated as possible determinants of vein thrombosis. These data indicate VWF as a potential therapeutic target in the management of VTE. Several studies report unselective antagonism of VWF for drugs used in daily clinical practice, including heparin and statins. Selective inhibition of VWF pathway has recently been tested in animal models of arterial and venous thrombosis as a novel therapeutic strategy to prevent platelet aggregation and thrombosis, promote vein lumen recanalization, and improve vein valve competency with excellent safety profile. In this review, we summarize the role of VWF in VTE, focusing on clinical and potential therapeutic implications.

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“…21 An imbalance in VWF/ADAMTS-13 axis is also involved in common thrombotic disorders, such as stroke, coronary artery disease, and venous thromboembolism (VTE). 22…”

Section: Vwf Activity Modulation: the Role Of Adamts-13mentioning

confidence: 99%

Section: Heparinmentioning

confidence: 99%

Section: Heparinmentioning

confidence: 99%

Section: Heparinmentioning

confidence: 99%

Section: Specific Therapiesmentioning

confidence: 99%

See 3 more Smart Citations

von Willebrand Factor and Venous Thromboembolism: Pathogenic Link and Therapeutic Implications

Calabrò

Gragnano

Golia

et al. 2017

Semin Thromb Hemost

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Acquired von Willebrand syndrome and factor VIII in patients with moderate to severe mitral regurgitation undergoing transcatheter mitral valve repair

Meindl

Paulus

Koller

et al. 2020

Clinical Cardiology

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Background and Hypothesis The acquired von Willebrand syndrome (AvWS), which predisposes to bleeding events, is often related to valvular heart diseases. We investigated possible implications of AvWS and factor VIII levels in patients with moderate to severe mitral regurgitation (MR) undergoing transcatheter mitral valve repair (TMVR). Methods and Results 123 patients with moderate to severe MR were prospectively enrolled. Complete measurements of von Willebrand Factor activity (vWFAct), von Willebrand Factor antigen (vWFAg), and factor VIII expression before and 4 weeks after TMVR were available in 85 patients. At baseline, seven patients had a history of gastrointestinal bleeding, two patients suffered bleeding events during their hospital stay, and one patient had a bleeding 4 weeks after TMVR. Even though vWFAct, vWFAct/vWFAg ratio and vWFAg values did not change after TMVR, we observed a significantly lower vWFAct/vWFAg ratio in patients with primary MR as compared to patients with secondary MR both at baseline (p = 0.022) and 4 weeks following the TMVR procedure (p = 0.003). Additionally, patients with a mean mitral valve gradient ≥4 mmHg after TMVR had significantly lower vWFAct/vWFAg ratios as compared to patients with a mean mitral valve gradient <4 mmHg (p = 0.001). Conclusions MR of primary etiology was associated with lower vWFAct/vWFAg ratio, hinting toward HMWM loss due to shear stress caused by eccentric regurgitation jets. In addition, morphological changes leading to postprocedural transmitral gradients ≥4 mmHg were related to lower vWFAct/vWFAg ratio 4 weeks after the procedure. Alterations of the vWFAct/vWFAg ratio in turn did not translate into a greater risk for bleeding events.

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Drug delivery systems for cardiovascular ailments

Pan

Jeevanandam

Acquah

et al. 2021

Drug Delivery Devices and Therapeutic Systems

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Von Willebrand Factor and Cardiovascular Disease: From a Biochemical Marker to an Attractive Therapeutic Target

Abstract: We provide an overview of the drugs that a have a role in VWF-antagonism, illustrating how they might become a potential option to overcome current limitations of antithrombotic therapy.

Cited by 32 publications

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von Willebrand Factor and Venous Thromboembolism: Pathogenic Link and Therapeutic Implications

von Willebrand Factor and Venous Thromboembolism: Pathogenic Link and Therapeutic Implications

Acquired von Willebrand syndrome and factor VIII in patients with moderate to severe mitral regurgitation undergoing transcatheter mitral valve repair

Drug delivery systems for cardiovascular ailments

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