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 PLA(2) 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. PLA_2 could therefore function as a connector between inflammation and fibrosis, the latter being an endpoint of chronic inflammation.
Oestvang
Janne
J
Department of Biology, Section for Molecular Biology and Biotechnology, Norwegian University of Science and Technology, N-7491 Trondheim, Norway.
Johansen
Berit
B
D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology* / Q000473:pathology; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism; D005355:Fibrosis / Q000201:enzymology / Q000473:pathology; D054501:Group II Phospholipases A2; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D008077:Lipoproteins, LDL; D008246:Lysophospholipids / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000201:enzymology* / Q000473:pathology; D010741:Phospholipases A / Q000378:metabolism*; D015398:Signal Transduction; D017539:Tunica Intima / Q000201:enzymology / Q000473:pathology
D015777:Eicosanoids; D008077:Lipoproteins, LDL; D008246:Lysophospholipids; D003094:Collagen; D010741:Phospholipases A; D054501:Group II Phospholipases A2