Platelet Reactive Oxygen Species, Oxidised Lipid Stress, Current Perspectives, and an Update on Future Directions

Abstract

Blood platelets are anucleate cells that play a vital role in haemostasis, innate immunity, angiogenesis, and wound healing. However, the inappropriate activation of platelets also contributes to vascular inflammation, atherogenesis, and thrombosis. Platelet activation is a highly complex receptor-mediated process that involves a multitude of signalling intermediates in which Reactive Oxygen Species (ROS) are proposed to play an important role. However, like for many cells, changes in the balance of ROS generation and/or scavenging in disease states may lead to the adoption of maladaptive platelet phenotypes. Here, we review the diverse roles of ROS in platelet function and how ROS are linked to specific platelet activation pathways. We also examine how changes in disease, particularly the plasma oxidised low-density lipoprotein (oxLDL), affect platelet ROS generation and platelet function.

Keywords: oxLDL; oxidative lipid stress; platelet ROS.

Figure 1

Signalling mechanisms involved in hyperlipidaemic-induced ROS production 399 and the downstream effects [23,79,80,81,82,83]. 8-iso-PGF2α, 8-iso-prostaglandin F2α; AA, arachidonic acid; cPLA₂, cytosolic phospholipase A_2; ERK5, extracellular signal-regulated kinase 5; mTOR, mechanistic target of rapamycin; NOX, NADPH oxidase; oxLDL, oxidised low-density lipoprotein; oxPC_CD36, oxidised phospholipid specific to CD36; p38MAPK, p38 mitogen-activated protein kinases; PCSK9, proprotein convertase subtilisin/kexin 9; PI3K/AKT, phosphoinositide-3-kinase/protein kinase B; PKC, protein kinase c; PKG, protein kinase G; PLCγ2, phospholipase C gamma 2; ROS, reactive oxygen species; SFK, Src family kinases; Syk, spleen-associated tyrosine kinase; TXA2, thromboxane A2; TXB2, thromboxane B2.