New phospholipase A(2) isozymes with a potential role in atherosclerosis.
OBJECTIVE
Inflammation is an integral feature of atherosclerosis, in which inflammatory processes contribute to the initiation, progression and rupture of lipid-rich atherosclerotic plaques. Recent studies have suggested the involvement of the proinflammatory secretory phospholipase A2 (sPLA2)-IIA in the development of atherosclerosis. This enzyme has been proposed to hydrolyze phosphatidylcholine (PC) in lipoproteins to liberate lyso-PC and free fatty acids in the arterial wall, thereby facilitating the accumulation of bioactive lipids and modified lipoproteins in atherosclerotic foci. However, the recent discovery of several novel sPLA2 isozymes has raised the question of which types of sPLA2 truly contribute to the atherosclerotic process.


RESULTS
Amongst the 10 mammalian sPLA2 isozymes, sPLA2-X, -V, -IIF and -III exhibit much more potent PC-hydrolyzing activity than do the others, and can release free fatty acids and lysophospholipids from the PC-rich outer leaflet of the cellular plasma membrane. In particular, sPLA2-X and sPLA2-V hydrolyze PC in lipoproteins far more efficiently than does sPLA2-IIA. Moreover, sPLA2-X promotes foam cell formation in vitro and is expressed in the atherosclerotic arterial walls of apolipoprotein E deficient mice in vivo.


CONCLUSIONS
PC-hydrolyzing sPLA2 isozymes, particularly sPLA2-V and sPLA2-X, are attractive candidates for proatherosclerotic factors that may act in place of sPLA2-IIA. However, their expression in human atherosclerotic lesions requires confirmation by specific methods that can distinguish between the different sPLA2 isozymes.
D000818:Animals; D001158:Arteries / Q000201:enzymology; D001161:Arteriosclerosis / Q000201:enzymology* / Q000209:etiology; D005227:Fatty Acids / Q000378:metabolism; D054501:Group II Phospholipases A2; D054509:Group X Phospholipases A2; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000209:etiology; D007527:Isoenzymes / Q000145:classification / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010741:Phospholipases A / Q000145:classification / Q000378:metabolism*; D054467:Phospholipases A2; D011509:Proteoglycans / Q000378:metabolism
D005227:Fatty Acids; D007527:Isoenzymes; D008074:Lipoproteins; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D011509:Proteoglycans; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054509:Group X Phospholipases A2; C516365:PLA2G10 protein, human; D054467:Phospholipases A2