CD36 and ERK5 link dyslipidemia to apoptotic-like platelet procoagulant function. Curr Opin Hematol 2019 Sep;26(5):357-365
Date
07/02/2019Pubmed ID
31261174Pubmed Central ID
PMC9308374DOI
10.1097/MOH.0000000000000522Scopus ID
2-s2.0-85070849797 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
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.
Author List
Yang M, Silverstein RLAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ApoptosisBlood Coagulation
CD36 Antigens
Dyslipidemias
Humans
Mitogen-Activated Protein Kinase 7
Platelet Activation
Signal Transduction
bcl-2 Homologous Antagonist-Killer Protein
bcl-2-Associated X Protein