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.[4] 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.[5]
Clinical significance
Lp-PLA2 is involved in the development of atherosclerosis,[3] 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.[7]
↑Tjoelker LW, Wilder C, Eberhardt C, Stafforini DM, Dietsch G, Schimpf B, Hooper S, Le Trong H, Cousens LS, Zimmerman GA, Yamada Y, McIntyre TM, Prescott SM, Gray PW (Apr 1995). "Anti-inflammatory properties of a platelet-activating factor acetylhydrolase". Nature. 374 (6522): 549–53. doi:10.1038/374549a0. PMID7700381.
↑Tew DG, Southan C, Rice SQ, Lawrence MP, Li H, Boyd HF, Moores K, Gloger IS, Macphee CH (Apr 1996). "Purification, properties, sequencing, and cloning of a lipoprotein-associated, serine-dependent phospholipase involved in the oxidative modification of low-density lipoproteins". Arteriosclerosis, Thrombosis, and Vascular Biology. 16 (4): 591–9. doi:10.1161/01.ATV.16.4.591. PMID8624782.
↑ 3.03.1Zalewski 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
Volume 1791, Issue 5, May 2009, Pages 327-338 PMID19272461 DOI: 10.1016/j.bbalip.2009.02.015
↑Mohler ER, Ballantyne CM, Davidson MH, Hanefeld M, Ruilope LM, Johnson JL, Zalewski A (Apr 2008). "The effect of darapladib on plasma lipoprotein-associated phospholipase A2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent: the results of a multicenter, randomized, double-blind, placebo-controlled study". Journal of the American College of Cardiology. 51 (17): 1632–41. doi:10.1016/j.jacc.2007.11.079. PMID18436114.
Yamada Y, Yokota M (Jul 1997). "Loss of activity of plasma platelet-activating factor acetylhydrolase due to a novel Gln281-->Arg mutation". Biochemical and Biophysical Research Communications. 236 (3): 772–5. doi:10.1006/bbrc.1997.7047. PMID9245731.
Mavoungou E, Georges-Courbot MC, Poaty-Mavoungou V, Nguyen HT, Yaba P, Delicat A, Georges AJ, Russo-Marie F (Sep 1997). "HIV and SIV envelope glycoproteins induce phospholipase A2 activation in human and macaque lymphocytes". Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology. 16 (1): 1–9. doi:10.1097/00042560-199709010-00001. PMID9377118.
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.
Min JH, Wilder C, Aoki J, Arai H, Inoue K, Paul L, Gelb MH (Apr 2001). "Platelet-activating factor acetylhydrolases: broad substrate specificity and lipoprotein binding does not modulate the catalytic properties of the plasma enzyme". Biochemistry. 40 (15): 4539–49. doi:10.1021/bi002600g. PMID11294621.
Quarck R, De Geest B, Stengel D, Mertens A, Lox M, Theilmeier G, Michiels C, Raes M, Bult H, Collen D, Van Veldhoven P, Ninio E, Holvoet P (May 2001). "Adenovirus-mediated gene transfer of human platelet-activating factor-acetylhydrolase prevents injury-induced neointima formation and reduces spontaneous atherosclerosis in apolipoprotein E-deficient mice". Circulation. 103 (20): 2495–500. doi:10.1161/01.cir.103.20.2495. PMID11369691.