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Apolipoprotein A-IV Binds αIIbβ3 Integrin and Inhibits Thrombosis

Apolipoprotein A-IV Binds αIIbβ3 Integrin and Inhibits Thrombosis

Xiaohong Ruby Xu, Yiming Wang, Reheman Adili, Lining Ju, Christopher M Spring, Joseph Wuxun Jin, Hong Yang, Miguel A D Neves, Pingguo Chen, Yan Yang, Xi Lei, Yunfeng Chen, Reid C Gallant, Miao Xu, Hailong Zhang, etc.

Nat Commun. 2018 Sep 6;9(1):3608.

PMID: 30190457

Abstract:

Platelet αIIbβ3 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 β3 integrin-coated beads. Binding of apoA-IV to platelets requires activation of αIIbβ3 integrin, and the direct apoA-IV-αIIbβ3 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 αIIbβ3 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 αIIbβ3 integrin and an endogenous inhibitor of thrombosis, establishing a link between lipoprotein metabolism and cardiovascular diseases.

Chemicals Related in the Paper:

Catalog Number	Product Name	CAS Number	Price
AP1118032	Azidotrimethyltin(IV)	1118-03-2	Price
AP6148487	Bromotrimethyllead(IV)	6148-48-7	Price
AP993522	Hexamethyldigermanium(IV)	993-52-2	Price

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