title: Purinergic Receptors in Thrombosis and Inflammation.
abstract: Under various pathological conditions, including thrombosis and inflammation, extracellular nucleotide levels may increase because of both active release and passive leakage from damaged or dying cells. Once in the extracellular compartment, nucleotides interact with plasma membrane receptors belonging to the P2 purinergic family, which are expressed by virtually all circulating blood cells and in most blood vessels. In this review, we focus on the specific role of the 3 platelet P2 receptors P2Y1, P2Y12, and P2X1 in hemostasis and arterial thrombosis. Beyond platelets, these 3 receptors, along with the P2Y2, P2Y6, and P2X7 receptors, constitute the main P2 receptors mediating the proinflammatory effects of nucleotides, which play important roles in various functions of circulating blood cells and cells of the vessel wall. Each of these P2 receptor subtypes specifically contributes to chronic or acute vascular inflammation and related diseases, such as atherosclerosis, restenosis, endotoxemia, and sepsis. The potential for therapeutic targeting of these P2 receptor subtypes is also discussed.
authors.affiliation: From the UMR_S949, INSERM, Strasbourg, France; Etablissement Français du Sang-Alsace (EFS-Alsace), Strasbourg, France; and Université de Strasbourg, Strasbourg, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Hechler
authors.affiliation: From the UMR_S949, INSERM, Strasbourg, France; Etablissement Français du Sang-Alsace (EFS-Alsace), Strasbourg, France; and Université de Strasbourg, Strasbourg, France. christian.gachet@efs.sante.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Gachet
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001777:Blood Coagulation; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D018836:Inflammation Mediators / Q000097:blood; D058910:Purinergic P2 Receptor Agonists / Q000627:therapeutic use; D058919:Purinergic P2 Receptor Antagonists / Q000627:therapeutic use; D011687:Purines / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2 / Q000378:metabolism; D015398:Signal Transduction; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D005343:Fibrinolytic Agents; D018836:Inflammation Mediators; C546468:P2RX7 protein, human; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011687:Purines; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D058473:Receptors, Purinergic P2Y2; C099845:purinoceptor P2Y6
keywords: atherosclerosis; inflammation; nucleotides; platelets; sepsis; thrombosis