Lysophosphatidylcholine and secretory phospholipase A2 in vascular disease: mediators of endothelial dysfunction and atherosclerosis.
Review
Overview
abstract
Lysophosphatidylcholine (LPC) is the major component of oxidized low density lipoprotein (oxLDL) and it has the ability to initiate or amplify several steps in atherogenesis due to its ability to impair endothelium-dependent vasorelaxation, enhance endothelial proliferation and permeability, stimulate adhesion and activation of lymphocytes, initiate chemotaxis of macrophages, impair migration and proliferation in vascular smooth muscle cells (SMCs), and modify platelet aggregation and coagulation pathways. For many of the LPC-induced effects, protein kinase C-dependent pathways have been implicated. In addition, modulation of ion current activity in the cell membrane, binding to a specific oxLDL receptor or to G-protein coupled receptors, as well as amplification of a highly oxidative state have all been postulated as likely mediating mechanisms. Secretory phopholipase A(2)-II (sPLA(2)-II) is one of the enzymes responsible for LPC production. sPLA(2)-II has been recently recognized as an independent risk factor for coronary artery disease. sPLA(2)-II favors the formation of bioactive lipids, stimulates SMC proliferation, activates macrophages enhancing lipid core formation and cytokine secretion, and binds to proteoglycans in the vessel wall matrix promoting lipid fusion and accumulation. The non-catalytic atherogenic effects of sPLA(2)-II are thought to be related to binding to an M-type receptor. Commonly used medications have been shown to decrease sPLA(2)-II activity generating a legitimate interest in the effects of the sPLA(2)-II pharmacologic antagonism. LPC and sPLA(2)-II are two very important mediators in atherosclerosis. Further research is warranted to clarify the cellular and molecular mechanisms that underlie their actions and to correlate in vitro data with clinical observations.
