Potential value of targeting von Willebrand factor in atherosclerotic cardiovascular disease

Abstract

Introduction: Animal studies show that von Willebrand factor (vWF) deficiency is associated with lower risks for atherosclerosis and atherothrombosis, including events such as acute myocardial infarction and ischemic stroke. vWF enables the binding of platelets along the damaged vessels leading to thrombogenesis. Interruption of this early stage of thrombus formation may prevent downstream amplification of the inflammatory and thrombotic processes that contribute to the plaque instability.

Areas covered: Increased levels of vWF have been related to the atherothrombotic complications and endothelial damage. Therefore, vWF has been suggested as a useful biomarker of endothelial damage/dysfunction. Preliminary data from Phase II trials in patients with acute myocardial infarction and thrombotic disorders have been promising, but many unanswered questions remain regarding the optimal therapeutic use of vWF blockade. This article describes the molecular structure of vWF, its functions and its interactions with the platelet membrane glycoprotein (GP) receptors GPIb and GPIIb-IIIa, as well as collagen. In addition, the article provides an overview of most promising investigational compounds tested as antithrombotic agents targeting vWF. Methods: Preclinical and clinical data for vWF blockage are discussed.

Expert opinion: The therapeutic approaches aiming to block the collagen-vWF-platelet axis have potentially beneficial effects for prevention and treatment of cardiovascular disease. However, the evidence directly associating vWF blockage with beneficial clinical outcomes is limited and needs further research. Optimal treatment regimes need to be established in relation of specific clinical circumstances and conditions.

Keywords::

• antagonist
• collagen
• glycoprotein
• monoclonal antibody
• platelet
• thrombosis
• von Willebrand factor

Declaration of interest

This work was supported by the Heart Research UK [RG 2579/09/10] and a European Society of Cardiology Research Grant. SMG holds a postdoctoral position from the Instituto de Salud Carlos III (Spain). Tables and figures have been prepared for this article by the authors and have not been published elsewhere.

Notes

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