دورية أكاديمية

Mice Lacking PECAM-1 and Ceacam1 Have Enhanced Platelet Secretion and Thrombus Growth: Novel Link with PAR4.

التفاصيل البيبلوغرافية
العنوان: Mice Lacking PECAM-1 and Ceacam1 Have Enhanced Platelet Secretion and Thrombus Growth: Novel Link with PAR4.
المؤلفون: Kuriri FA; Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, Victoria, Australia.; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Shaqra, Riyadh Province, Saudi Arabia., Burchall G; Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, Victoria, Australia., Alanazi F; Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, Victoria, Australia.; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences-AlQurayyat, Jouf University, Saudi Arabia., Antonipillai J; Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, Victoria, Australia., Dobie G; Department of Medical Laboratory Technology, Jazan University, Jazan, Saudi Arabia., Beachemin N; Department of Oncology, Medicine and Biochemistry, Goodman Cancer Research Centre, McGill University, Montreal, Canada., Jackson DE; Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, Victoria, Australia.
المصدر: Thrombosis and haemostasis [Thromb Haemost] 2022 Jun; Vol. 122 (6), pp. 961-973. Date of Electronic Publication: 2021 Dec 28.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Thieme Country of Publication: Germany NLM ID: 7608063 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2567-689X (Electronic) Linking ISSN: 03406245 NLM ISO Abbreviation: Thromb Haemost Subsets: MEDLINE
أسماء مطبوعة: Publication: 2018- : Stuttgart : Thieme
Original Publication: Stuttgart, Schattauer.
مواضيع طبية MeSH: P-Selectin*/metabolism , Thrombosis*/genetics , Thrombosis*/metabolism, Platelet Endothelial Cell Adhesion Molecule-1/*metabolism, Adenosine Diphosphate/metabolism ; Animals ; Antigens, CD ; Blood Platelets/metabolism ; Carcinoembryonic Antigen/metabolism ; Cell Adhesion Molecules ; Collagen/metabolism ; Mice ; Platelet Activation ; Platelet Aggregation ; Platelet Endothelial Cell Adhesion Molecule-1/genetics ; Receptors, Proteinase-Activated/metabolism ; Receptors, Purinergic/metabolism
مستخلص: The Ig-ITIM bearing receptors, PECAM-1 and CEACAM1, have been shown net negative regulators of platelet-collagen interactions and hemiITAM signaling pathways. In this study, a double knockout (DKO) mouse was developed with deleted PECAM-1 and CEACAM1 to study their combined contribution in platelet activation by glycoprotein VI, C-type lectin-like receptor 2, protease activated receptor (PAR4), ADP purinergic receptors, and thromboxane receptor (TP) A2 pathways. In addition, their collective contribution was examined in thrombus formation under high shear and microvascular thrombosis using in vivo models. DKO platelets responded normally to ADP purinergic receptors and the TP A2 pathway. However, DKO platelets released significantly higher amounts of P-selectin compared with hyper-responsive Pecam-1-/- or Ceacam1-/- versus wild-type (WT) upon stimulation with collagen-related peptide or rhodocytin. In contrast, DKO platelets showed increased amounts of P-selectin exposure upon stimulation with PAR4 agonist peptide or thrombin but not Pecam-1-/- , Ceacam1-/- , or WT platelets. Blockade of phospholipase C (PLC) or Rho A kinase revealed that DKO platelets enhanced α-granule release via PAR4/Gαq/PLC signaling without crosstalk with Src/Syk or G 12/13 signaling pathways. Severely delayed clot retraction in vitro was observed in DKO phenotype. The DKO model revealed a significant increase in thrombus formation compared with the hyper-responsive Ceacam1-/- or Pecam-1-/- versus WT phenotype. DKO platelets have similar glycoprotein surface expression compared with Pecam-1-/- , Ceacam1-/- , and WT platelets. This study demonstrates that PECAM-1 and CEACAM1 work in concert to negatively regulate hemiITAM signaling, platelet-collagen interactions, and PAR4 Gαq protein- coupled signaling pathways. Both PECAM-1 and CEACAM1 are required for negative regulation of platelet activation and microvascular thrombosis in vivo.
Competing Interests: None declared.
(Thieme. All rights reserved.)
المشرفين على المادة: 0 (Antigens, CD)
0 (CD66 antigens)
0 (Carcinoembryonic Antigen)
0 (Ceacam1 protein, mouse)
0 (Cell Adhesion Molecules)
0 (P-Selectin)
0 (Pecam1 protein, mouse)
0 (Platelet Endothelial Cell Adhesion Molecule-1)
0 (Receptors, Proteinase-Activated)
0 (Receptors, Purinergic)
61D2G4IYVH (Adenosine Diphosphate)
9007-34-5 (Collagen)
تواريخ الأحداث: Date Created: 20211007 Date Completed: 20220706 Latest Revision: 20220809
رمز التحديث: 20221213
DOI: 10.1055/a-1663-8108
PMID: 34619794
قاعدة البيانات: MEDLINE
الوصف
تدمد:2567-689X
DOI:10.1055/a-1663-8108