Lipoprotein-Associated Phospholipase A2 Activity (PLAC®)

The PLAC® test for Lp-PLA2 Activity is an enzyme assay for the in vitro quantitative determination of Lp-PLA2 (lipoprotein-associated phospholipase A2) activity in EDTA plasma and serum. Lp-PLA2 activity is to be used in conjunction with clinical evaluation and patient risk assessment as an aid in predicting risk of coronary heart disease (CHD) in patients with no prior history of cardiovascular events.

Lp-PLA2 is a calcium-independent phospholipase A2 enzyme that is associated with both low-density lipoprotein (LDL) and, to a lesser extent, high-density lipoprotein (HDL) in human plasma and serum1 and is distinct from other such phospholipases such as cPLA2 and sPLA2.2,3 Lp-PLA2 is produced by macrophages and other inflammatory cells and is expressed in greater concentrations in advanced atherosclerotic lesions than early-stage lesions.4,5

Several lines of evidence suggest that oxidation of LDL plays a critical step in the development and progression of atherosclerosis.6,7 Lp-PLA2 participates in the breakdown of oxidized LDL in the vascular wall by hydrolyzing the oxidized phospholipid, producing lysophosphatidylcholine and oxidized free fatty acids, both of which are potent pro-inflammatory products that contribute to the formation of atherosclerotic plaques.8-10

Lp-PLA2 has demonstrated modest intra- and inter-individual variation, commensurate with other cardiovascular lipid markers and substantially less variability than high sensitivity C-reactive protein (hs-CRP). In addition, Lp-PLA2 is not elevated in systemic inflammatory conditions, and may be a more specific marker of vascular inflammation. The relatively small biological variation of Lp-PLA2 and its vascular specificity are of value in the detection and monitoring of cardiovascular risk.11-13

1. Zalewski A, Macphee C. Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology, epidemiology, and possible therapeutic target. Arterioscler Thromb Vasc Biol. 2005 May;25(5):923-931. PubMed 15731492

2. Kudo I, Murakami M. Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:3-58. PubMed 12432908

3. Burke JE, Dennis EA. Phospholipase A2 structure/function, mechanism, and signaling. J Lipid Res. 2009 Apr;50:s237-242. PubMed 19011112

4. Hakkinen T, Luoma JS, Hiltunen MO, et al. Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase, is expressed by macrophages in human and rabbit atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 1999 Dec;19(12):2909-2917. PubMed 10591668

5. Kolodgie FD, Burke AP, Skorija KS, et al. Lipoprotein-associated phospholipase A2 protein expression in the natural progression of human coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2523-2529. PubMed 16960105

6. Witztum JL. The oxidation hypothesis of atherosclerosis. Lancet. 1994 Sep;344(8925):793-795. PubMed 7916078

7. Chisolm GM, Steinberg D. The oxidative modification hypothesis of atherogenesis: an overview. Free Radic Biol Med. 2000 Jun 15;28(12):1815-1826. PubMed 10946223

8. Macphee CH, Moores KE, Boyd HF, et al. Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor. Biochem J. 1999 Mar 1;338(Pt 2):479-487. PubMed 10024526

9. Macphee CH. Lipoprotein-associated phospholipase A2: a potential new risk factor for coronary artery disease and a therapeutic target. Curr Opin Pharmacol. 2001 Apr;1(2):121-125. PubMed 11714085

10. Suckling KE, Macphee CH. Lipoprotein-associated phospholipase A2: a target directed at the atherosclerotic plaque. Expert Opin Ther Targets. 2002 Jun;6(3):309-314. PubMed 12223071

11. Wolfert RL, Kim NW, Selby RG, Sarno MJ, Warnick GR, Sudhir K. Biological variability and specificity of lipoprotein-associated phospholipase A2 (Lp-PLA), a novel marker of cardiovascular risk (abstract). Circulation. 2004;110(Supplement 3):309.

12. Lerman A, McConnell JP. Lipoprotein-associated phospholipase A2: a risk marker or a risk factor? Am J Cardiol. 2008 Jun 16;101(12A):11F-22F. PubMed 18549867

13. Thompson A, Gao P, Orfei L, et al. Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet. 2010 May 1;375(9725):1536-1544. PubMed 20435228