Role of Lipoprotein-Associated Phospholipase A2 in Atherosclerosis

The development of atherosclerotic vascular disease is invariably linked to the formation of bioactive lipid mediators and accompanying vascular inflammation. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that is produced by inflammatory cells, co-travels with circulating low-density lipoprotein (LDL), and hydrolyzes oxidized phospholipids in LDL. Its biological role has been controversial with initial reports purporting atheroprotective effects of Lp-PLA2 thought to be a consequence of degrading platelet-activating factor and removing polar phospholipids in modified LDL. Recent studies, however, focused on pro-inflammatory role of Lp-PLA2 mediated by products of the Lp-PLA2 reaction (lysophosphatidylcholine and oxidized nonesterified fatty acids). These bioactive lipid mediators, which are generated in lesion-prone vasculature and to a lesser extent in the circulation (eg, in electronegative LDL), are known to elicit several inflammatory responses. The proinflammatory action of Lp-PLA2 i...