In the blood, Lp-PLA2 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]
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, two 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]
^Tew DG, Southan C, Rice SQ, Lawrence MP, Li H, Boyd HF, et al. (April 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.
^Tellis CC, Tselepis AD (May 2009). "The role of lipoprotein-associated phospholipase A2 in atherosclerosis may depend on its lipoprotein carrier in plasma". Biochimica et Biophysica Acta. 1791 (5): 327–38. doi:10.1016/j.bbalip.2009.02.015. PMID19272461.
^Mohler ER, Ballantyne CM, Davidson MH, Hanefeld M, Ruilope LM, Johnson JL, Zalewski A (April 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 (July 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.
Hiramoto M, Yoshida H, Imaizumi T, Yoshimizu N, Satoh K (December 1997). "A mutation in plasma platelet-activating factor acetylhydrolase (Val279-->Phe) is a genetic risk factor for stroke". Stroke. 28 (12): 2417–20. doi:10.1161/01.str.28.12.2417. PMID9412624.
Yamada Y, Ichihara S, Fujimura T, Yokota M (February 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, et al. (September 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. doi:10.1055/s-0037-1615214. PMID9759612. S2CID23924021.
