Type 2 scavenger receptor CD36 in platelet activation: the role of hyperlipemia and oxidative stress

Abstract

Platelet hyper-reactivity and a systemic prothrombotic state are associated with atherosclerosis and other inflammatory conditions. CD36, a member of the Type 2 scavenger receptor family, is a multiligand pattern recognition receptor that recognizes specific oxidized phospholipids, molecules expressed on microbial pathogens, apoptotic cells, and cell-derived microparticles. Recent studies have demonstrated that CD36 binding to oxidized LDL or microparticles activates a specific signaling pathway that induces platelet activation. This pathway is activated in vivo in the setting of hyperlipidemia and oxidant stress. Genetic deletion of CD36 protects mice from pathological thrombosis associated with hyperlipidemia without any apparent effect on normal hemostasis. Targeting CD36 or its signaling pathway could potentially lead to the development of novel antithrombotic therapies for patients with atheroinflammatory disorders.

Pravastatin and simvastatin improves acetylsalicylic acid‐mediated in vitro blood platelet inhibition

“…A significant role of CD36 in modulating platelet reactivity and in promoting of a prothrombotic state in settings, where CD36 ligands (oxLDL, cell‐derived microparticles and apoptotic cells) are present, was described [16]. In our study, we showed that simvastatin and pravastatin may modulate platelet reactivity in a concentration‐dependent manner by reducing the CD36 abundance on the platelet surface.…”

CD36‐dependent signaling mediates fatty acid‐induced gut release of secretin and cholecystokinin

“…A cell line stably expressing a mutated form of CD36 (CD36K/A) that lacks CD36‐mediated signaling to intracellular calcium was also used. The C terminus of CD36 is important for signal transduction (44, 45). In the CD36K/A mutant lysines K469 and K472 in the C terminus were substituted with alanine.…”

Diverse CD36 expression among Japanese population: defective CD36 mutations cause platelet and monocyte CD36 reductions in not only deficient but also normal phenotype subjects

“…However, some researchers have suggested that a lack of CD36 on monocytes/macrophages inhibits the removal of oxLDL from circulating plasma, leading to increased plasma oxLDL levels and consequently augmenting atherogenesis [2,27]. In platelets, oxLDL induces or enhances platelet activation in a CD36-dependent manner, and this is associated with the prothrombotic phenotype in patients with dyslipidemia [28][29][30][31]. Thus, the interaction between oxLDL and platelet CD36 underlying atherosclerosis may be involved in thrombus formation at the site of ruptured plaque, termed atherothrombosis.…”