Lysophospholipids: two-faced mediators in atherosclerosis

As risk factors for atherosclerosis and major constituents of atherosclerotic lesions, lipids have long been regarded as instrumental in the development of this disease. Apart from their structural contribution to lesion development, lipids may also modulate processes, both in circulation and in the plaque, which are instrumental in this vasculopathy. This review focuses on two major bioactive phospholipids, lysophosphaticlic acid and sphingosine 1-phosphate, which were recently shown to be potentially important mediators in atherogenesis. These lysolipids display a dysregulated biosynthesis during atherosclerosis and are rather complementary in their mode of action. They both act as agonists of G-protein-coupled receptor family members on all vascular wall cell types involved in atherosclerosis, rendering them attractive targets for therapeutic intervention. This review will outline the current knowledge on their homeostasis, their physiological activity in various inflammatory and vascular wall cells and the implications of this for atherosclerosis.