Defense mechanisms neutralizing oxidized phospholipids

Human blood contains phospholipids, some of which are prone to oxidation. Oxidized phospholipids (OxPLs) are toxic and pro-inflammatory substances that are both markers and makers in several pathologies, including atherosclerosis. In order to prevent accumulation of OxPLs and development of their harmful effects, blood plasma contains natural defense mechanisms. These include enzymatic neutralization of OxPLs, binding of antibodies and other plasma proteins to OxPLs, and removal of OxPLs by endocytotic receptors. We hypothesize that the mechanisms that inactivate atherogenic OxPLs are not less important for atherogenesis than the processes that generate these bad lipids. The project will apply mass spectrometry of lipids and proteins in order to characterize enzymatic modifications of OxPLs and to identify OxPL-binding proteins that mask OxPLs and thus prevent damage of cellular targets. The project will provide new insights into the mechanisms detoxifying OxPLs in blood plasma and thus improve our understanding of the balance between the pro- and anti-atherogenic processes, which determines an individual risk of cardiovascular disease.