Phospholipase A(2) in vascular disease.
Secretory phospholipase A(2) (PLA(2)) can be proatherogenic both in the circulation and in the arterial wall. In blood plasma, PLA(2) can modify the circulating lipoproteins and so induce formation of small dense LDL particles, which are associated with increased risk for cardiovascular disease. In the arterial wall, PLA(2) can hydrolyze lipoproteins. The PLA(2)-modified lipoproteins bind tightly to extracellular proteoglycans, which may lead to their enhanced retention in the arterial wall. The modified lipoproteins may also aggregate and fuse, which can lead to accumulation of their lipids within the extracellular matrix. The PLA(2)-modified particles are more susceptible to further modifications by other enzymes and agents and can be taken up by macrophages, leading to accumulation of intracellular lipids. In addition, lysophospholipids and free fatty acids, the hydrolysis products of PLA(2), promote atherogenesis. Thus, these lipid mediators can be carried, either by the PLA(2)-modified lipoproteins themselves or by albumin, into the arterial cells, which then undergo functional alterations. This may, in turn, lead to specific changes in the extracellular matrix, which increase the retention and accumulation of lipoproteins within the matrix. In the present article, we discuss the possible actions of PLA(2) enzymes, especially PLA(2)-IIA, in the arterial wall during atherogenesis.
Hurt-Camejo
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AstraZeneca R&D, Cell Biology and Biochemistry, Mölndal, Sweden. Eva.Hurt-Camejo@astrazeneca.com
Camejo
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G
Peilot
H
H
Oörni
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K
Kovanen
P
P
D000818:Animals; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism; D001161:Arteriosclerosis / Q000201:enzymology / Q000209:etiology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D054501:Group II Phospholipases A2; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D051379:Mice; D005810:Multigene Family; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D017539:Tunica Intima / Q000503:physiopathology; D017540:Tunica Media / Q000503:physiopathology; D014652:Vascular Diseases / Q000201:enzymology*
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D005230:Fatty Acids, Nonesterified; D008074:Lipoproteins; D008246:Lysophospholipids; D011509:Proteoglycans; D010741:Phospholipases A; D054501:Group II Phospholipases A2