1. Antiplatelet effects of the CEACAM1-derived peptide QDTT
- Author
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Yujia Ye, Min Leng, Shengjie Chai, Lihong Yang, Longcheng Ren, Wen Wan, Huawei Wang, Longjun Li, Chaozhong Li, and Zhaohui Meng
- Subjects
Antithrombotic effects ,carcinoembryonic antigen-related cell adhesion molecule 1 ,convulxin ,peptides ,platelet activation ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
AbstractCarcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) restricts platelet activation via platelet collagen receptor GPVI/FcRγ-chain. In this study, screening against collagen-induced platelet aggregation was performed to identify functional CEACAM1 extracellular domain fragments. CEACAM1 fragments, including Ala-substituted peptides, were synthesized. Platelet assays were conducted on healthy donor samples for aggregation, cytotoxicity, adhesion, spreading, and secretion. Mice were used for tail bleeding and FeCl3-induced thrombosis experiments. Clot retraction was assessed using platelet-rich plasma. Extracellular segments of CEACAM1 and A1 domain-derived peptide QDTT were identified, while N, A2, and B domains showed no involvement. QDTT inhibited platelet aggregation. Ala substitution for essential amino acids (Asp139, Thr141, Tyr142, Trp144, and Trp145) in the QDTT sequence abrogated collagen-induced aggregation inhibition. QDTT also suppressed platelet secretion and “inside-out” GP IIb/IIIa activation by convulxin, along with inhibiting PI3K/Akt pathways. QDTT curtailed FeCl3-induced mesenteric thrombosis without significantly prolonging bleeding time, implying the potential of CEACAM1 A1 domain against platelet activation without raising bleeding risk, thus paving the way for novel antiplatelet drugs.
- Published
- 2024
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