| Title: |
Platelet integrin αIIbβ3 plays a key role in a venous thrombogenesis mouse model |
| Authors: |
Brian D. Adair; Conroy O. Field; José L. Alonso; Jian-Ping Xiong; Shi-Xian Deng; Hyun Sook Ahn; Eivgeni Mashin; Clary B. Clish; Johannes van Agthoven; Mark Yeager; Youzhong Guo; David A. Tess; Donald W. Landry; Mortimer Poncz; M. Amin Arnaout |
| Source: |
Nature Communications, Vol 15, Iss 1, Pp 1-14 (2024) |
| Publisher Information: |
Nature Portfolio, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Science |
| Subject Terms: |
Science |
| Description: |
Abstract Venous thrombosis (VT) is a common vascular disease associated with reduced survival and a high recurrence rate. VT is initiated by the accumulation of platelets and neutrophils at sites of endothelial cell activation. A role for platelet αIIbβ3 in VT is not established, a task complicated by the increased bleeding risk caused by partial agonists such as tirofiban. Here, we show that m-tirofiban, a modified version of tirofiban, does not agonize αIIbβ3 based on lack of neoepitope expression and the cryo-EM structure of m-tirofiban/full-length αIIbβ3 complex. m-tirofiban abolishes agonist-induced platelet aggregation while preserving clot retraction ex vivo and, unlike tirofiban, it suppresses venous thrombogenesis in a mouse model without increasing bleeding. These findings establish a key role for αIIbβ3 in VT initiation and suggest that m-tirofiban and compounds with a similar structurally-defined mechanism of action merit consideration as potential thromboprophylaxis agents in patients at high risk for VT and hemorrhage. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
https://doaj.org/toc/2041-1723 |
| DOI: |
10.1038/s41467-024-52869-3 |
| Access URL: |
https://doaj.org/article/5cb4e38292ca4761ba710d35e201c213 |
| Accession Number: |
edsdoj.5cb4e38292ca4761ba710d35e201c213 |
| Database: |
Directory of Open Access Journals |