Antiplatelet effects of the CEACAM1-derived peptide QDTT

Autor: Yujia Ye, Min Leng, Shengjie Chai, Lihong Yang, Longcheng Ren, Wen Wan, Huawei Wang, Longjun Li, Chaozhong Li, Zhaohui Meng
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Platelets, Vol 35, Iss 1 (2024)
Druh dokumentu: article
ISSN: 09537104
1369-1635
0953-7104
DOI: 10.1080/09537104.2024.2308635
Popis: Carcinoembryonic 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.
Databáze: Directory of Open Access Journals
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