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Apolipoprotein A-IV binds αIIbβ3 integrin and inhibits thrombosis
Xiaohong Ruby Xu1,2,3,4, Yiming Wang1,2,5, Reheman Adili2
1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, M5S 1A1.
Nature Communications
|September 8, 2018
Summary
Apolipoprotein A-IV (apoA-IV) binds to platelet αIIbβ3 integrin, inhibiting platelet aggregation. This discovery links lipoprotein metabolism to cardiovascular disease prevention.
Area of Science:
- Biochemistry
- Hematology
- Cardiovascular Science
Background:
- Platelet αIIbβ3 integrin is crucial for thrombosis and hemostasis.
- Dysregulation of platelet activity contributes to myocardial infarction and stroke.
Purpose of the Study:
- To identify novel ligands of platelet αIIbβ3 integrin.
- To investigate the role of apolipoprotein A-IV (apoA-IV) in platelet function and thrombosis.
Main Methods:
- Isolation of apoA-IV from human plasma using αIIbβ3 integrin-coated beads.
- Detection of apoA-IV-αIIbβ3 interaction using a single-molecule Biomembrane Force Probe.
- Analysis of apoA-IV's effect on platelet aggregation and postprandial hyperactivity.
Main Results:
- Apolipoprotein A-IV (apoA-IV) directly binds to activated platelet αIIbβ3 integrin.
- Specific N-terminal aspartic acids (5 and 13) of apoA-IV are essential for αIIbβ3 binding.
- ApoA-IV inhibits platelet aggregation and postprandial platelet hyperactivity.
- Human apoA-IV plasma levels exhibit a circadian rhythm negatively correlating with platelet aggregation.
Conclusions:
- ApoA-IV is identified as a novel endogenous ligand and inhibitor of platelet αIIbβ3 integrin.
- ApoA-IV plays a significant role in regulating thrombosis and hemostasis.
- This study establishes a link between lipoprotein metabolism and cardiovascular disease prevention via apoA-IV modulation of platelet activity.
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