Platelet-derived S100 family member myeloid-related protein-14 regulates thrombosis. J Clin Invest 2014 May;124(5):2160-71
Date
04/03/2014Pubmed ID
24691441Pubmed Central ID
PMC4001535DOI
10.1172/JCI70966Scopus ID
2-s2.0-84899762473 (requires institutional sign-in at Scopus site) 109 CitationsAbstract
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.
Author List
Wang Y, Fang C, Gao H, Bilodeau ML, Zhang Z, Croce K, Liu S, Morooka T, Sakuma M, Nakajima K, Yoneda S, Shi C, Zidar D, Andre P, Stephens G, Silverstein RL, Hogg N, Schmaier AH, Simon DIAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlood Platelets
CD36 Antigens
Calgranulin B
Carotid Artery Diseases
Female
Gene Expression Regulation
Humans
Male
Mice, Knockout
Thrombosis
