Phospholipase A2 and small, dense low-density lipoprotein.
High levels of small, dense LDL in plasma are associated with increased risk for cardiovascular disease. There are some biochemical characteristics that may render small, dense LDL particles more atherogenic than larger, buoyant LDL particles. First, small, dense LDL particles contain less phospholipids and unesterified cholesterol in their surface monolayer than do large, buoyant LDL particles. This difference in lipid content appears to induce changes in the conformation of apolipoprotein B-100, leading to more exposure of proteoglycan-binding regions. This may be one reason for the high-affinity binding of small, dense LDL to arterial proteoglycans. Reduction of the phospholipid content in the surface monolayer LDL by treatment with secretory phospholipase A2 (sPLA2) forms small, dense LDL with an enhanced tendency to interact with proteoglycans. Circulating levels of sPLA2-IIA appears to be an independent risk factor for coronary artery disease and a predictor of cardiovascular events. In addition, in-vivo studies support the hypothesis that sPLA2 proteins contribute to atherogenesis and its clinical consequences. These data suggest that modification of LDL by sPLA2 in the arterial tissue or in plasma may be a mechanism for the generation of atherogenic lipoprotein particles in vivo, with a high tendency to be entrapped in the arterial extracellular matrix.
Hurt-Camejo
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Wallenberg Laboratory, Götenberg University, Sweden. Eva.Hurt@wlab.wall.gu.se
Camejo
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Sartipy
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D000818:Animals; D001161:Arteriosclerosis / Q000097:blood* / Q000209:etiology*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D010316:Particle Size; D010741:Phospholipases A / Q000097:blood* / Q000378:metabolism; D054467:Phospholipases A2; D011509:Proteoglycans / Q000097:blood
D008077:Lipoproteins, LDL; D011509:Proteoglycans; D010741:Phospholipases A; D054467:Phospholipases A2