title: Platelet-derived S100 family member myeloid-related protein-14 regulates thrombosis.
abstract: Expression of the gene encoding the S100 calcium-modulated protein family member MRP-14 (also known as S100A9) is elevated in platelets from patients presenting with acute myocardial infarction (MI) compared with those from patients with stable coronary artery disease; however, a causal role for MRP-14 in acute coronary syndromes has not been established. Here, using multiple models of vascular injury, we found that time to arterial thrombotic occlusion was markedly prolonged in Mrp14⁻/⁻ mice. We observed that MRP-14 and MRP-8/MRP-14 heterodimers (S100A8/A9) are expressed in and secreted by platelets from WT mice and that thrombus formation was reduced in whole blood from Mrp14⁻/⁻ mice. Infusion of WT platelets, purified MRP-14, or purified MRP-8/MRP-14 heterodimers into Mrp14⁻/⁻ mice decreased the time to carotid artery occlusion after injury, indicating that platelet-derived MRP-14 directly regulates thrombosis. In contrast, infusion of purified MRP-14 into mice deficient for both MRP-14 and CD36 failed to reduce carotid occlusion times, indicating that CD36 is required for MRP-14-dependent thrombosis. Our data identify a molecular pathway of thrombosis that involves platelet MRP-14 and CD36 and suggest that targeting MRP-14 has potential for treating atherothrombotic disorders, including MI and stroke.
authors.forename: Yunmei
authors.initials: Y
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Fang
authors.forename: Huiyun
authors.initials: H
authors.lastname: Gao
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Bilodeau
authors.forename: Zijie
authors.initials: Z
authors.lastname: Zhang
authors.forename: Kevin
authors.initials: K
authors.lastname: Croce
authors.forename: Shijian
authors.initials: S
authors.lastname: Liu
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Morooka
authors.forename: Masashi
authors.initials: M
authors.lastname: Sakuma
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Nakajima
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yoneda
authors.forename: Can
authors.initials: C
authors.lastname: Shi
authors.forename: David
authors.initials: D
authors.lastname: Zidar
authors.forename: Patrick
authors.initials: P
authors.lastname: Andre
authors.forename: Gillian
authors.initials: G
authors.lastname: Stephens
authors.forename: Roy L
authors.initials: RL
authors.lastname: Silverstein
authors.forename: Nancy
authors.initials: N
authors.lastname: Hogg
authors.forename: Alvin H
authors.initials: AH
authors.lastname: Schmaier
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Simon
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D040502:Calgranulin B / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002340:Carotid Artery Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008297:Male; D018345:Mice, Knockout; D013927:Thrombosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018955:CD36 Antigens; D040502:Calgranulin B; C576329:S100A9 protein, mouse