Lysophosphatidylcholine is a Major Component of Platelet Microvesicles Promoting Platelet Activation and Reporting Atherosclerotic Plaque Instability

Abstract

Background Microvesicles (MVs) are small cell-derived vesicles, which are mainly released by activated cells. They are part of a communication network delivering biomolecules, for example, inflammatory molecules, via the blood circulation to remote cells in the body. Platelet-derived MVs are known to induce vascular inflammation. Research on the mediators and mechanisms of their inflammatory effects has attracted major interest. We hypothesize that specific lipids are the mediators of vascular inflammation caused by platelet-derived MVs. Methods and Results Liquid chromatography electrospray ionization-tandem mass spectrometry was used for lipid profiling of platelet-derived MVs. Lysophosphatidylcholine (LPC) was found to be a major component of platelet-derived MVs. Investigating the direct effects of LPC, we found that it induces platelet activation, spreading, migration and aggregation as well as formation of inflammatory platelet-monocyte aggregates. We show for the first time that platelets express the LPC receptor G2AR, which mediates LPC-induced platelet activation. In a mouse model of atherosclerotic plaque instability/rupture, circulating LPC was detected as a surrogate marker of plaque instability. These findings were confirmed by matrix-assisted laser desorption ionization imaging, which showed that the LPC concentration of human plaques was highest in vulnerable plaque regions.

Platelet lipidome: Dismantling the “Trojan horse” in the bloodstream

“…Given its effect on vascular smooth muscle cells (VSMCs), platelet‐derived LPA may substantially contribute to atheroprogression. Recently LPC has been suggested as a surrogate marker of plaque instability in atherosclerotic mice, and as a principal component of platelet‐derived microvesicles . LPC activates platelets through G2AR (Figure ).…”

“…Leukotrienes (LTs) cause inflammation in asthma, while lipoxins terminate inflammation . LPC as a platelet chemoattractant promotes the formation of platelet–monocyte aggregates, the predominance of which is seen in peripheral circulation of ACS patients . Monocytes are a prime source of soluble tissue factor (TF) in blood, further substantiated by cardiovascular risk factors, eg, hypercholesterolemia; exaggerated by the presence of platelets; and reverted by statin administration .…”

Novel Approaches to Fine-Tune Therapeutic Targeting of Platelets in Atherosclerosis: A Critical Appraisal

“…78 Furthermore, the comparison of the platelet lipid profiles from CAD patients with matched controls reveals that LPC is weakly detectable in platelets of healthy persons, but increased by several orders of magnitude in CAD patients and also found in vulnerable atherosclerotic plaques. 79,80 LPC has been reported to be concentrated in microvesicles from activated platelets which are important markers and factors in vascular inflammation and atherosclerosis. 81 Lipid profiling of platelet MV identified differences in the composition with higher amounts of PC and LPC compared with the activated parent platelets.…”

“…81 Lipid profiling of platelet MV identified differences in the composition with higher amounts of PC and LPC compared with the activated parent platelets. 80 Platelets express the lysophospholipid receptor G2A/GPR132 that is responsible for platelet activation through LPC. 80 LPA, a derivative of LPC, is implicated in platelet activation and atherosclerosis signaling through G-protein-coupled receptors of the LPAR (EDG) family.…”

“…80 Platelets express the lysophospholipid receptor G2A/GPR132 that is responsible for platelet activation through LPC. 80 LPA, a derivative of LPC, is implicated in platelet activation and atherosclerosis signaling through G-protein-coupled receptors of the LPAR (EDG) family. LPA is produced by platelets through phospholipase A1 and autotaxin and is one active component of mildly oxidized LDL and atherosclerotic plaques in platelet activation.…”