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In the blood it travels mainly with low-density lipoprotein (LDL). Less than 20% is associated with high-density lipoprotein HDL. Several lines of evidence suggest that HDL-associated Lp-PLA2 may substantially contribute to the HDL antiatherogenic activities.[8] It is an enzyme produced by inflammatory cells and hydrolyzes oxidized phospholipids in LDL.
Lp-PLA2 is platelet-activating factor (PAF) acetylhydrolase (EC 3.1.1.47), a secreted enzyme that catalyzes the degradation of PAF to inactive products by hydrolysis of the acetyl group at the sn-2 position, producing the biologically inactive products LYSO-PAF and acetate.[9]
Clinical significance
Lp-PLA2 is involved in the development of atherosclerosis,[7] an observation that has prompted interest as a possible therapeutic target (see, e.g. the investigational drug Darapladib). In human atherosclerotic lesions, 2 main sources of Lp-PLA2 can be identified, including that which is brought into the intima bound to LDL (from the circulation), and that which is synthesized de novo by plaque inflammatory cells (macrophages, T cells, mast cells)."
A meta-analysis involving a total of 79,036 participants in 32 prospective studies found that Lp-PLA2 levels are positively correlated with increased risk of developing coronary heart disease and stroke.[11]
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^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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^ abZalewski A, Macphee C (May 2005). "Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology, epidemiology, and possible therapeutic target". Arteriosclerosis, Thrombosis, and Vascular Biology. 25 (5): 923–31. doi:10.1161/01.ATV.0000160551.21962.a7. PMID15731492.
^The role of lipoprotein-associated phospholipase A2 in atherosclerosis may depend on its lipoprotein carrier in plasma. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
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Hiramoto M, Yoshida H, Imaizumi T, Yoshimizu N, Satoh K (Dec 1997). "A mutation in plasma platelet-activating factor acetylhydrolase (Val279-->Phe) is a genetic risk factor for stroke". Stroke: A Journal of Cerebral Circulation. 28 (12): 2417–20. doi:10.1161/01.str.28.12.2417. PMID9412624.
Yamada Y, Ichihara S, Fujimura T, Yokota M (Feb 1998). "Identification of the G994--> T missense in exon 9 of the plasma platelet-activating factor acetylhydrolase gene as an independent risk factor for coronary artery disease in Japanese men". Metabolism. 47 (2): 177–81. doi:10.1016/S0026-0495(98)90216-5. PMID9472966.
Yoshida H, Imaizumi T, Fujimoto K, Itaya H, Hiramoto M, Yoshimizu N, Fukushi K, Satoh K (Sep 1998). "A mutation in plasma platelet-activating factor acetylhydrolase (Val279Phe) is a genetic risk factor for cerebral hemorrhage but not for hypertension". Thrombosis and Haemostasis. 80 (3): 372–5. PMID9759612.
Lecointe N, Meerabux J, Ebihara M, Hill A, Young BD (May 1999). "Molecular analysis of an unstable genomic region at chromosome band 11q23 reveals a disruption of the gene encoding the alpha2 subunit of platelet-activating factor acetylhydrolase (Pafah1a2) in human lymphoma". Oncogene. 18 (18): 2852–9. doi:10.1038/sj.onc.1202645. PMID10362256.
Howard KM, Olson MS (Jun 2000). "The expression and localization of plasma platelet-activating factor acetylhydrolase in endotoxemic rats". The Journal of Biological Chemistry. 275 (26): 19891–6. doi:10.1074/jbc.M001462200. PMID10748027.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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