The Role of CD36/GPIV in Platelet Biology

Abstract

CD36 (also known as platelet glycoprotein IV) is expressed by a variety of different cell entities, where it possesses functions as a signaling receptor, but additionally acts as a transporter for long-chain fatty acids. This dual function of CD36 has been investigated for its relevance in immune and nonimmune cells. Although CD36 was first identified on platelets, the understanding of the role of CD36 in platelet biology remained scarce for decades. In the past few years, several discoveries have shed a new light on the CD36 signaling activity in platelets. Notably, CD36 has been recognized as a sensor for oxidized low-density lipoproteins in the circulation that mitigates the threshold for platelet activation under conditions of dyslipidemia. Thus, platelet CD36 transduces atherogenic lipid stress into an increased risk for thrombosis, myocardial infarction, and stroke. The underlying pathways that are affected by CD36 are the inhibition of cyclic nucleotide signaling pathways and simultaneously the induction of activatory signaling events. Furthermore, thrombospondin-1 secreted by activated platelets binds to CD36 and furthers paracrine platelet activation. CD36 also serves as a binding hub for different coagulation factors and, thus, contributes to the plasmatic coagulation cascade. This review provides a comprehensive overview of the recent findings on platelet CD36 and presents CD36 as a relevant target for the prevention of thrombotic events for dyslipidemic individuals with an elevated risk for thrombosis.

CD36 as a gatekeeper of myocardial lipid metabolism and therapeutic target for metabolic disease

“…The emphasis is on the fatty acid transport function of CD36 within the cardiovascular system, as it has been most extensively studied in this context. We do not discuss the role of CD36 in other tissues but refer the reader to more comprehensive reviews on CD36 in platelet biology (8), in atherosclerosis (9,10), in intestine (11), in liver and nonalcoholic fatty liver disease (12,13), in the central nervous system (14), and in cancer (15)(16)(17)(18)(19).…”

Targeting Cysteine Oxidation in Thrombotic Disorders

“…Oxidation of LDL (oxLDL) creates a high-affinity ligand for the scavenger receptor CD36 [68,69], a transmembrane glycoprotein of the innate immune system that is expressed on multiple vascular cells and was first identified as the fourth-largest major membrane protein on platelets [70]. Recognition of oxLDL by platelet CD36 promotes multiple signaling events that link to desensitization of platelet inhibitory pathways [54,71,72] or sensitization of platelet activation pathways [55,71,73]. A comprehensive understanding of platelet CD36 signaling is still an active area of research and has recently been reviewed [71].…”

“…Recognition of oxLDL by platelet CD36 promotes multiple signaling events that link to desensitization of platelet inhibitory pathways [54,71,72] or sensitization of platelet activation pathways [55,71,73]. A comprehensive understanding of platelet CD36 signaling is still an active area of research and has recently been reviewed [71].…”