The role of phospholipases in lipid modification and atherosclerosis.
Phospholipases have received wide attention as it has become clear that several isoforms of the phospholipase family play a role in onset and progression of atherosclerosis. The release of free fatty acids (FFA) and lysophospholipids (lysoPL) provide metabolites for various inflammatory pathways, and this has been considered the main mechanism of phospholipase-driven inflammation. However, generation of FFA and lysoPL are only part of the story. The induction of low-density phospholipoprotein (LDL) aggregation and accumulation, receptor binding, co-regulation with cyclooxygenase (COX) and lip-oxygenase (LO) pathways, internalization through heparan sulfate proteoglycan (HSPG) shuttling, and crosstalk between phospholipases all play a role in atherosclerosis.Group IIA phospholipase has long been considered a key enzyme in the initiation of various inflammatory diseases, but new data also indicate a role in the subsequent resolution of inflammatory processes. Recently, secreted group V and group X phospholipase and platelet activating factor acetylhydrolase (PAF-AH) are also recognized as important enzymes in atherosclerosis, modifying LDL and leading to lipid accumulation. The phospholipases and their function in atherosclerosis are not fully under-stood. Future investigations can deliver better insight in the complex role of these enzymes. The present review summarizes the current state of phospholipase research related to atherosclerosis.
Ghesquiere
Stijn A I
SA
Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
Hofker
Marten H
MH
de Winther
Menno P J
MP
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001161:Arteriosclerosis / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D010740:Phospholipases / Q000502:physiology*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism
D000975:Antioxidants; D007527:Isoenzymes; D008077:Lipoproteins, LDL; D010740:Phospholipases; D013108:Sphingomyelin Phosphodiesterase