Lyso-PC and macrophage interplay. Scavenging through the fatty side of atherosclerosis

Atherosclerosis is triggered by LDL entrapment in the vessel wall. Oxidation and enzymatic processing of LDL give rise to inflammatory mediators such as lyso-PC. These inflammatory mediators attract monocytes into the vessel wall where they differentiate into macrophages. The macrophages adopt different phenotypes depending on the environment.
In vitro, ex vivo, and in vivo studies were combined to elucidate the role of lyso-PC on the macrophage phenotype and how lyso-PC and monocytes correlate to the clinical outcome. Lyso-PC was shown to stimulate and sustain inflammation, and to promote differentiation of pro-inflammatory classically activated macrophages. The content of lyso-PC in plaques removed from patients correlated to a detrimental plaque phenotype with high concentrations of pro-inflammatory cytokines, increased lipid content, lower levels of smooth muscle cells, and increased levels of pro-inflammatory macrophages. The CD14++CD16- monocyte subpopulation was shown to predict cardiovascular events.
Today, the treatments available reduce the risk of cardiovascular events by approximately 40%. To further reduce the risk, more accurate treatments have to be designed. These treatments need to selectively modulate pro-atherosclerotic mechanisms, in contrast to the systemic alternatives that are in use today. Altogether, the impact of lyso-PC on plaque phenotype and on clinical outcome suggests that treatments pinpointed on the pro-inflammatory mechanism induced by lyso-PC could be relevant.