Platelet activation and prothrombotic mediators at the nexus of inflammation and atherosclerosis: Potential role of antiplatelet agents. (January 2021)

• Record Type: Journal Article
• Authors: Lordan, Ronan; Tsoupras, Alexandros; Zabetakis, Ioannis
• Is Part Of: Blood reviews. Volume 45(2021)
• Publication Date: 2021-01
• Subjects: Atherosclerosis -- Inflammation -- Thromboxane -- ADP -- Thrombin -- Platelet-activating factor -- Antiplatelet therapy; AA Arachidonic acid -- ADP Adenosine diphosphate -- ATP Adenosine triphosphate -- COX Cyclooxygenase -- CVD Cardiovascular diseases -- CCL2 Chemokine (C-C motif) ligand 2 -- CXCL1 Chemokine (C-X-C motif) ligand 1 -- DTS Dense tubular system -- ECGF Platelet-derived endothelial cell growth factor -- IGF-1 Insulin-like growth factor -- IP3 Inositol-1, 4, 5-triphosphate -- ITAM Immunoreceptor tyrosine-based activation motifs -- LAMP Lysosomal-associated membrane proteins -- LPA Platelet-derived lysophosphatidic acid -- MAC-1 Macrophage-1 antigen -- MAPK Mitogen-activated protein kinases -- MCP-1 Monocyte chemoattractant protein-1 -- M-CSF Macrophage colony-stimulating factor -- MMPs Matrix metalloproteinases -- NETs Neutrophil extracellular traps -- NO Nitric oxide -- OCS Open canicular system -- PAF Platelet-activating factor -- PAFLL Platelet-activating factor-like lipids -- PAF-R Platelet-activating factor-receptor -- PAR Protease-activated receptor -- PDGF Platelet-derived growth factor -- PDI Protein disulphide isomerase -- PGE2 Prostaglandin E2 -- PGI2 Prostacyclin I2 -- PI3K Phosphoinositide-3 kinase -- PLCγ2 phospholipase Cγ2 -- PMNs Polymorphonuclear neutrophils -- PSGL-1 P-selectin glycoprotein ligand-1 -- RANTES Regulated on activation, normal T expressed and secreted -- SP-1 Sphingosine-1-phosphate -- SNARE Soluble N-ethylmaleimide-sensitive factor-attachment protein receptors -- TF Tissue factor -- TFPI Tissue factor pathway inhibitor -- TGF-β Transforming growth factor β -- TLRs Toll-like receptors -- TLR9 Toll-like receptor 9 -- TRAP Thrombin receptor-activating peptide -- TxA2 Thromboxane A2 -- VAMP-8 Vesicle-associated membrane protein 8 -- VEGF Vascular endothelial growth factor -- VWF von Willebrand factor; Hematology -- Periodicals; Hematology -- Periodicals; Hématologie -- Périodiques; Hematology; Electronic journals; Periodicals; 616.15
• DOI: 10.1016/j.blre.2020.100694
• Languages: English
• ISSNs: 0268-960X

Abstract

Abstract: Platelets are central to inflammation-related manifestations of cardiovascular diseases (CVD) such as atherosclerosis. Platelet-activating factor (PAF), thrombin, thromboxane A2 (TxA2 ), and adenosine diphosphate (ADP) are some of the key agonists of platelet activation that are at the intersection between a plethora of inflammatory pathways that modulate pro-inflammatory and coagulation processes. The aim of this article is to review the role of platelets and the relationship between their structure, function, and the interactions of their constituents in systemic inflammation and atherosclerosis. Antiplatelet therapies are discussed with a view to primary prevention of CVD by the clinical reduction of platelet reactivity and inflammation. Current antiplatelet therapies are effective in reducing cardiovascular risk but increase bleeding risk. Novel therapeutic antiplatelet approaches beyond current pharmacological modalities that do not increase the risk of bleeding require further investigation. There is potential for specifically designed nutraceuticals that may become safer alternatives to pharmacological antiplatelet agents for the primary prevention of CVD but there is serious concern over their efficacy and regulation, which requires considerably more research.