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血管性血友病因子在心血管疾病诊断与治疗中的应用:最新进展与展望

Von Willebrand factor in diagnostics and treatment of cardiovascular disease: Recent advances and prospects.

作者信息

Kozlov Sergey, Okhota Sergey, Avtaeva Yuliya, Melnikov Ivan, Matroze Evgeny, Gabbasov Zufar

机构信息

Department of Problems of Atherosclerosis, National Medical Research Centre of Cardiology Named After Academician E.I. Chazov of the Ministry of Health of the Russian Federation, Moscow, Russia.

Laboratory of Cell Hemostasis, National Medical Research Centre of Cardiology Named After Academician E.I. Chazov of the Ministry of Health of the Russian Federation, Moscow, Russia.

出版信息

Front Cardiovasc Med. 2022 Dec 2;9:1038030. doi: 10.3389/fcvm.2022.1038030. eCollection 2022.

Abstract

Von Willebrand factor (VWF) is a large multimeric glycoprotein involved in hemostasis. It is essential for platelet adhesion to the subendothelium of the damaged endothelial layer at high shear rates. Such shear rates occur in small-diameter arteries, especially at stenotic sites. Moreover, VWF carries coagulation factor VIII and protects it from proteolysis in the bloodstream. Deficiency or dysfunction of VWF predisposes to bleeding. In contrast, an increase in the concentration of high molecular weight multimers (HMWM) of VWF is closely associated with arterial thrombotic events. Severe aortic stenosis (AS) or hypertrophic obstructive cardiomyopathy (HOCM) can deplete HMWM of VWF and lead to cryptogenic, gastrointestinal, subcutaneous, and mucosal bleeding. Considering that VWF facilitates primary hemostasis and a local inflammatory response at high shear rates, its dysfunction may contribute to the development of coronary artery disease (CAD) and its complications. However, current diagnostic methods do not allow for an in-depth analysis of this contribution. The development of novel diagnostic techniques, primarily microfluidic, is underway. Such methods can provide physiologically relevant assessments of VWF function at high shear rates; however, they have not been introduced into clinical practice. The development and use of agents targeting VWF interaction with the vessel wall and/or platelets may be reasonable in prevention of CAD and its complications, given the prominent role of VWF in arterial thrombosis.

摘要

血管性血友病因子(VWF)是一种参与止血的大型多聚体糖蛋白。在高剪切速率下,它对于血小板黏附于受损内皮层的内皮下至关重要。这种剪切速率出现在小直径动脉中,尤其是在狭窄部位。此外,VWF携带凝血因子VIII并保护其在血流中免受蛋白水解。VWF缺乏或功能障碍易导致出血。相反,VWF高分子量多聚体(HMWM)浓度增加与动脉血栓形成事件密切相关。严重主动脉瓣狭窄(AS)或肥厚性梗阻性心肌病(HOCM)可消耗VWF的HMWM并导致不明原因的胃肠道、皮下和黏膜出血。鉴于VWF在高剪切速率下促进初级止血和局部炎症反应,其功能障碍可能促成冠状动脉疾病(CAD)及其并发症的发生。然而,目前的诊断方法无法深入分析这种作用。新型诊断技术,主要是微流控技术,正在研发中。这些方法可以在高剪切速率下提供与VWF功能相关的生理学评估;然而,它们尚未应用于临床实践。鉴于VWF在动脉血栓形成中的突出作用,开发和使用针对VWF与血管壁和/或血小板相互作用的药物可能对预防CAD及其并发症是合理的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdd7/9755348/d1cd6404a882/fcvm-09-1038030-g001.jpg

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