PhospholipaseA2:: A key regulator of inflammatory signalling and a connector to fibrosis development in atherosclerosis

Atherosclerosis is a progressive inflammatory disease that takes place in the intima of the arterial wall. It is characterized by activation of endothelial cells, proliferation of smooth muscle cells and macrophages, accumulation of lipoproteins, deposition of extracellular matrix components and enhanced lipolytic enzyme activity. Phospholipase A(2) (PLA(2)) has been postulated to play an important role in the inflammatory process of atherosclerosis, but its molecular mechanism is uncertain. The secretory PLA2 is expressed at increased levels in an atherosclerotic plaque and may hydrolyze low-density lipoproteins (LDL). This action promotes the production of pro-inflammatory lipids such as lysophospholipids, unsaturated fatty acids and eicosanoids. The current review highlights recent findings on how LDL-derived lipid mediators, generated by sPLA(2) modification of LDL, regulate pro-inflammatory activation and intracellular signaling in macrophages. Moreover, the review discusses how PLA(2) enzymes regulate signalling that promotes collagen accumulation and fibrotic plaque development. PLA2 could therefore function as a connector between inflammation and fibrosis, the latter being an endpoint of chronic inflammation. (c) 2006 Elsevier B.V. All rights reserved.