Dual roles of fucoidan-GPIbα interaction in thrombosis and hemostasis: implications for drug development targeting GPIbα

doi:10.1016/j.jtha.2022.12.030

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	Dual roles of fucoidan-GPIbα interaction in thrombosis and hemostasis: implications for drug development targeting GPIbα
	Shen,Chuanbin; Mackeigan,Daniel T.; Shoara,Aron A.; Xu,Runjia; Bhoria,Preeti; Karakas,Danielle; Ma,Wenjing; Cerenzia,Eric; Chen,ZiYan; Hoard,Brock; Lin,Lisha; Lei,Xi; Zhu,Guangheng; Chen,Pingguo; Johnson,Philip E.; Ni,Heyu
	2023
发表期刊	JOURNAL OF THROMBOSIS AND HAEMOSTASIS
ISSN	1538-7836
卷号	21 期号:5 页码:1274-1288
摘要	Background: Platelet GPIb & alpha;-von Willebrand factor (VWF) interaction initiates platelet adhesion, activation, and thrombus growth, especially under high shear conditions. Therefore, the GPIb-VWF axis has been suggested as a promising target against arterial thrombosis. The polysaccharide fucoidan has been reported to have opposing prothrombotic and antithrombotic effects; however, its binding mechanism with platelets has not been adequately studied. Objective: The objective of this study was to explore the mechanism of fucoidan and its hydrolyzed products in thrombosis and hemostasis. Methods: Natural fucoidan was hydrolyzed by using hydrochloric acid and was char-acterized by using size-exclusion chromatography, UV-visible spectroscopy, and flu-orometry techniques. The effects of natural and hydrolyzed fucoidan on platelet aggregation were examined by using platelets from wild-type, VWF and fibrinogen-deficient, GPIb & alpha;-deficient, and IL4R & alpha;/GPIb & alpha;-transgenic and & alpha;IIb-deficient mice and from human beings. Platelet activation markers (P-selectin expression, PAC-1, and fibrinogen binding) and platelet-VWF A1 interaction were measured by using flow cytometry. GPIb & alpha;-VWF A1 interaction was evaluated by using enzyme-linked immu-nosorbent assay. GPIb-IX-induced signal transduction was detected by using western blot. Heparinized whole blood from healthy donors was used to test thrombus for-mation and growth in a perfusion chamber. Results: We found that GPIb & alpha; is critical for fucoidan-induced platelet activation. Fucoidan interacted with the extracellular domain of GPIb & alpha; and blocked its interaction with VWF but itself could lead to GPIb & alpha;-mediated signal transduction and, subsequently, & alpha;IIb & beta;3 activation and platelet aggregation. Conversely, low-molecular weight fucoidan inhibited GPIb-VWF-mediated platelet aggregation, spreading, and thrombus growth at high shear. Conclusion: Fucoidan-GPIb & alpha; interaction may have unique therapeutic potential against bleeding disorders in its high-molecular weight state and protection against arterial thrombosis by blocking GPIb-VWF interaction after fucoidan is hydrolyzed.
关键词	fucoidan glycoprotein Ib platelet thrombosis von Willebrand factor VON-WILLEBRAND-FACTOR PLATELET GLYCOPROTEIN IB MOLECULAR-WEIGHT FUCOIDAN ARTERIAL THROMBOSIS IX AGGREGATION RECEPTOR ACTIVATION FIBRINOGEN INTEGRIN
DOI	10.1016/j.jtha.2022.12.030
收录类别	SCI
WOS记录号	WOS:001041075200001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75439
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Shen,Chuanbin,Mackeigan,Daniel T.,Shoara,Aron A.,et al. Dual roles of fucoidan-GPIbα interaction in thrombosis and hemostasis: implications for drug development targeting GPIbα[J]. JOURNAL OF THROMBOSIS AND HAEMOSTASIS,2023,21(5):1274-1288.
APA	Shen,Chuanbin.,Mackeigan,Daniel T..,Shoara,Aron A..,Xu,Runjia.,Bhoria,Preeti.,...&Ni,Heyu.(2023).Dual roles of fucoidan-GPIbα interaction in thrombosis and hemostasis: implications for drug development targeting GPIbα.JOURNAL OF THROMBOSIS AND HAEMOSTASIS,21(5),1274-1288.
MLA	Shen,Chuanbin,et al."Dual roles of fucoidan-GPIbα interaction in thrombosis and hemostasis: implications for drug development targeting GPIbα".JOURNAL OF THROMBOSIS AND HAEMOSTASIS 21.5(2023):1274-1288.

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