| First Author | Xu XR | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 3608 |
| PubMed ID | 30190457 | Mgi Jnum | J:267726 |
| Mgi Id | MGI:6268248 | Doi | 10.1038/s41467-018-05806-0 |
| Citation | Xu XR, et al. (2018) Apolipoprotein A-IV binds alphaIIbbeta3 integrin and inhibits thrombosis. Nat Commun 9(1):3608 |
| abstractText | Platelet alphaIIbbeta3 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 beta3 integrin-coated beads. Binding of apoA-IV to platelets requires activation of alphaIIbbeta3 integrin, and the direct apoA-IV-alphaIIbbeta3 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 alphaIIbbeta3 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 alphaIIbbeta3 integrin and an endogenous inhibitor of thrombosis, establishing a link between lipoprotein metabolism and cardiovascular diseases. |
