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

Author(s):  
Felice Gragnano ◽  
Enrica Golia ◽  
Francesco Natale ◽  
Renatomaria Bianchi ◽  
Ivana Pariggiano ◽  
...  
Vascular ◽  
2020 ◽  
Vol 28 (3) ◽  
pp. 309-313
Author(s):  
Da Li ◽  
Xiaosong Zhang ◽  
Honggang Zhang ◽  
Xiaoqiang Li

Objectives In cardiovascular disease, deep vein thrombosis is one of the vital symptoms causing pulmonary thromboembolism. However, the pathogenesis of deep vein thrombosis is still not clear. One of the critical factors leading to deep vein thrombosis is the platelet aggregation that is mediated by a set of key genes including platelet membrane protein coded by platelet glycoprotein Ib alpha chain (GPIBA). Methods Deep vein thrombosis model was established according to the previous protocol, and venous blood and thrombi were collected for further analysis. Results The dynamic changes of GPIBA and coagulation factor, von Willebrand factor, were observed in deep vein thrombosis models. Meanwhile, critical proteins participating in adhesion and binding of platelets such as epithelial membrane protein 2 (EMP2), vascular cell adhesion protein 1 (VCAM1), immunoreceptor tyrosine-based activation motif 1 (ITAM1), integrin subunit alpha M (ITGAM), or fibronectin were also differentially expressed in deep vein thrombosis models. Conclusions Application of heparin could reverse these dynamic changes in deep vein thrombosis models. Thus, we explained the potential synergic role of GPIBA and von Willebrand factor in regulating the occurrence of deep vein thrombosis and provide therapeutic target against cardiovascular disease.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nawfal Mihyawi ◽  
MUHAMMAD AJMAL ◽  
Jun Hung ◽  
Beeletsega T Yeneneh

Introduction: Von Willebrand factor (vWF) plays an important role in the coagulation process at the site of vascular injury. It is unclear whether vWF deficiency is protective against cardiovascular disease (CVD) since investigations are limited in this entity. Hypothesis: Our study assessed the hypothesis that the prevalence of CVD is less in patients with than without Von Willebrand disease (vWD). Methods: We queried the National Inpatient Sample (NIS) from 2009-2014. Entire data was used with exclusion of patients below 18 and over 75-year-old. We defined cardiovascular disease as any event of myocardial infarction or a diagnosis of ischemic heart disease using the International Classification of Disease, 9th edition (ICD-9). The primary outcome of interest was to compare the odds ratio of CVD in patients with and without vWD. Results: A total of 224,475,443 weighted hospital discharge samples were identified. Of these, 82,809 carried a diagnosis of vWD. The odds of CVD were less common in vWD patients (OR 0.54; 95% CI 0.52 - 0.56) (table 1). After multivariate logistic regression analysis, with adjustment for age, gender and the most common CVD risk factors including hypertension, smoking, diabetes, hyperlipidemia, family history of CVD, chronic kidney disease and obesity the likelihood of CVD remained lower in vWD patients (OR 0.65; 95% CI 0.63-0.67) (table 2). Conclusions: Our study, the first to involve a large cohort of patients, demonstrated that vWF deficiency is associated with decreased prevalence of CVD. Hence, vWF could potentially be a therapeutic target in CVD management. More investigations are needed for confirmation of these findings and to determine causation.


Circulation ◽  
2008 ◽  
Vol 118 (24) ◽  
pp. 2533-2539 ◽  
Author(s):  
David S. Frankel ◽  
James B. Meigs ◽  
Joseph M. Massaro ◽  
Peter W.F. Wilson ◽  
Christopher J. O'Donnell ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Felice Gragnano ◽  
Simona Sperlongano ◽  
Enrica Golia ◽  
Francesco Natale ◽  
Renatomaria Bianchi ◽  
...  

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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