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CD36 and ERK5 link dyslipidemia to apoptotic-like platelet procoagulant function

Yang, Mouaa,b; Silverstein, Roy L.b,c

doi: 10.1097/MOH.0000000000000522
HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier

Purpose of review Metabolic diseases, including dyslipidemia, diabetes mellitus, and chronic inflammation are risk factors for clinically significant thrombotic events. Thrombosis in these settings is multifaceted with coordinated mechanisms between platelet activation and the hemostatic pathways. This review focuses on recent advances in platelet procoagulant and apoptotic signaling with emphasis on the pathophysiologic mechanisms induced by platelet CD36 in dyslipidemia, and the key unaddressed questions relating to the field.

Recent findings CD36 promotes platelet activation and increases the risk for thrombosis through signaling events. These include generation of reactive oxygen species, activation of redox-sensitive MAP kinase ERK5, and promotion of a pro-thrombotic phenotype. CD36 promotes phosphatidylserine externalization leading to a procoagulant function downstream from MAP kinase ERK5 that is separate from a pro-aggregatory function. Phosphatidylserine externalization requires maladaptive caspase activation, promotes assembly of the factor tenase and prothrombinase complex, and promotes fibrin formation. It is distinct from the canonical pathways mediating platelet procoagulant function by strong physiologic stimuli or by the platelet apoptotic-like Bak/Bax-mediated pathway for cellular clearance.

Summary Understanding CD36 signaling in the context of dyslipidemia, or other metabolic diseases will identify important and novel signaling hubs that could be potential therapeutic targets for intervention without impacting hemostasis.

aDepartment of Biochemistry, Medical College of Wisconsin

bBlood Research Institute, Versiti Blood Center of Wisconsin

cDepartment of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

Correspondence to Roy L. Silverstein, MD, Medical College of Wisconsin, Hub for Medical Collaboration, Rm 8745, 8701 West Watertown Plank Road, Milwaukee, WI 53226, USA. Tel: +1 414 955 0518; fax: +1 414 955 0524; e-mail:

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