Apolipoprotein A-IV binds αIIbβ3 integrin and inhibits thrombosis

被引：87

作者：

Xu, Xiaohong Ruby ^{[1
,2
,3
,4
,5
]}

Wang, Yiming ^{[1
,2
,3
,6
]}

Adili, Reheman ^{[2
,3
]}

Ju, Lining ^{[7
,8
,9
,10
]}

Spring, Christopher M. ^{[2
,3
]}

Jin, Joseph Wuxun ^{[2
,3
,6
]}

Yang, Hong ^{[2
,3
,6
]}

Neves, Miguel A. D. ^{[2
,3
]}

Chen, Pingguo ^{[2
,3
,6
]}

Yang, Yan ^{[2
,3
,6
]}

Lei, Xi ^{[2
,3
]}

Chen, Yunfeng ^{[8
,11
]}

Gallant, Reid C. ^{[1
,2
,3
]}

Xu, Miao ^{[1
,2
,3
]}

Zhang, Hailong ^{[2
,3
]}

Song, Jina ^{[2
,3
,6
]}

Ke, Peifeng ^{[5
,12
]}

Zhang, Dan ^{[2
,3
,5
]}

Carrim, Naadiya ^{[2
,3
,6
]}

Yu, Si-Yang ^{[2
,3
,13
]}

Zhu, Guangheng ^{[2
,3
]}

She, Yi-Min ^{[14
,15
]}

Cyr, Terry ^{[14
,15
]}

Fu, Wenbin ^{[4
,5
]}

Liu, Guoqing ^{[16
]}

Connelly, Philip W. ^{[1
,2
,3
]}

Rand, Margaret L. ^{[1
,17
]}

Adeli, Khosrow ^{[1
,18
]}

Freedman, John ^{[1
,2
,3
,19
]}

Lee, Jeffrey E. ^{[1
]}

Tso, Patrick ^{[20
]}

Marchese, Patrizia ^{[21
]}

Davidson, W. Sean ^{[20
]}

Jackson, Shaun P. ^{[9
,10
,21
]}

Zhu, Cheng ^{[7
,8
,11
]}

Ruggeri, Zaverio M. ^{[21
]}

Ni, Heyu ^{[1
,2
,3
,6
,19
,22
]}

机构：

[1] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada

[2] St Michaels Hosp, Dept Lab Med, Keenan Res Ctr Biomed Sci, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada

[3] Toronto Platelet Immunobiol Grp, Toronto, ON M5B 1W8, Canada

[4] Guangdong Prov Hosp Chinese Med, Dept Acupuncture & Moxibust, Guangzhou 510120, Guangdong, Peoples R China

[5] Guangzhou Univ Chinese Med, Guangzhou 510000, Guangdong, Peoples R China

[6] Canadian Blood Serv Ctr Innovat, Toronto, ON M5G 2M1, Canada

[7] Georgia Inst Technol, Coulter Dept Biomed Engn, Atlanta, GA 30332 USA

[8] Georgia Inst Technol, Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA

[9] Univ Sydney, Heart Res Inst, Camperdown, NSW 20069, Australia

[10] Univ Sydney, Charles Perkins Ctr, Camperdown, NSW 20069, Australia

[11] Georgia Inst Technol, Woodruff Sch Mech Engn, Atlanta, GA 30332 USA

[12] Guangdong Prov Hosp Chinese Med, Dept Lab Med, Guangzhou 510120, Guangdong, Peoples R China

[13] Cent South Univ, Dept Cardiovasc Med, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China

[14] Hlth Canada, Ctr Biol Res Biol, HPFB, Ottawa, ON K1A 0M2, Canada

[15] Hlth Canada, Genet Therapies Directorate, HPFB, Ottawa, ON K1A 0M2, Canada

[16] Peking Univ, Inst Cardiovasc Sci, Hlth Sci Ctr, Beijing 100083, Peoples R China

[17] Hosp Sick Children, Div Haematol Oncol, Toronto, ON M5G 1X8, Canada

[18] Hosp Sick Children, Program Mol Struct & Funct, Toronto, ON M5G 1X8, Canada

[19] Univ Toronto, Dept Med, Toronto, ON M5S 1A1, Canada

[20] Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH 45219 USA

[21] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA

[22] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A1, Canada

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

美国国家卫生研究院; 加拿大健康研究院; 加拿大创新基金会;

关键词：

HIGH-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; VON-WILLEBRAND-FACTOR; P-SELECTIN; IN-VIVO; GLYCOPROTEIN-IIB/IIIA; PLATELET-AGGREGATION; PLASMA-FIBRINOGEN; TISSUE FACTOR; MICE;

D O I：

10.1038/s41467-018-05806-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Platelet alpha IIb beta 3 integrin and its ligands are essential for thrombosis and hemostasis, and play key roles in myocardial infarction and stroke. Here we show that apolipoprotein A-IV (apoA-IV) can be isolated from human blood plasma using platelet beta 3 integrin-coated beads. Binding of apoA-IV to platelets requires activation of alpha IIb beta 3 integrin, and the direct apoA-IV-alpha IIb beta 3 interaction can be detected using a single-molecule Biomembrane Force Probe. We identify that aspartic acids 5 and 13 at the N-terminus of apoA-IV are required for binding to alpha IIb beta 3 integrin, which is additionally modulated by apoA-IV C-terminus via intra-molecular interactions. ApoA-IV inhibits platelet aggregation and postprandial platelet hyperactivity. Human apoA-IV plasma levels show a circadian rhythm that negatively correlates with platelet aggregation and cardiovascular events. Thus, we identify apoA-IV as a novel ligand of alpha IIb beta 3 integrin and an endogenous inhibitor of thrombosis, establishing a link between lipoprotein metabolism and cardiovascular diseases.

引用

页数：18

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