Von Willebrand Factor and cardiovascular disease: from a biochemical marker to an attractive therapeutic target
| Autor: | Paolo Calabrò, Renatomaria Bianchi, Mariagiovanna Russo, Enrica Golia, Ivana Pariggiano, Plinio Cirillo, Vincenzo Diana, Mario Crisci, Felice Gragnano, Fabio Fimiani, Giuseppe Limongelli, Francesco Natale |
|---|---|
| Přispěvatelé: | Gragnano, Felice, Golia, Enrica, Natale, Francesco, Bianchi, Renatomaria, Pariggiano, Ivana, Crisci, Mario, Diana, Vincenzo, Fimiani, Fabio, Limongelli, Giuseppe, Russo, Mariagiovanna, Cirillo, Plinio, Calabrò, Paolo, Russo, Maria giovanna |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Blood Platelets
Platelet Aggregation Population Context (language use) Disease 030204 cardiovascular system & hematology Bioinformatics 03 medical and health sciences Platelet Adhesiveness 0302 clinical medicine Fibrinolytic Agents Von Willebrand factor hemic and lymphatic diseases von Willebrand Factor Antithrombotic Animals Humans Medicine Platelet 030212 general & internal medicine Thrombus education Pharmacology education.field_of_study biology business.industry valvular heart disease medicine.disease Disease Models Animal Cardiovascular Diseases Drug Design Immunology cardiovascular system biology.protein Cardiology and Cardiovascular Medicine business Biomarkers circulatory and respiratory physiology |
| Popis: | Background Despite recent advances, there is still an unmet need in antithrombotic therapy. New drugs have to overcome old targets, looking for new complementary strategies to counteract thrombus formation and propagation. Since its initial recognition in the 50's, von Willebrand Factor (VWF) has proved to be a contributor in clot formation. The contribution of VWF to platelet adhesion and aggregation is pivotal at high shear rates (i.e. microcirculation and critical artery stenosis), where globular-inactive-VWF elongates in a long chain-active conformation. Particularly, at sites of plaque erosion/disruption the activation of VWF may contribute critically to post-stenotic thrombus formation. In this context, VWF is a potential target of antithrombotic therapies. The plasma concentration of VWF increases in high risk population and predicts cardiovascular (CV) outcome. VWF demonstrates an emerging role in different clinical settings; for example, in valvular heart disease where it has been recently proposed as a new fluido-dynamic marker of disease severity and a predictor of successful correction. Drugs used in daily clinical practice (LMWHs, statins, N-acetylcysteine, glycoprotein IIb/IIIa inhibitors) may have an unselective antagonism on the VWF-pathway. Recently, several "tailor-made" inhibitors of VWF have been investigated. In animal models and clinical studies monoclonal antibodies, aptamers and nanobodies have been demonstrated to directly interfere with the VWF pathway. These studies proved the powerful antithrombotic property and the acceptable level of safety of this strategy. Conclusion 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|