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Clinical Chemistry 52: 1645-1650, 2006. First published July 27, 2006; 10.1373/clinchem.2006.070672
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(Clinical Chemistry. 2006;52:1645-1650.)
© 2006 American Association for Clinical Chemistry, Inc.

Minireview

Lp-PLA2: A New Kid on the Block

Andrew Zalewski1,4,a, Jeanenne J. Nelson2, Lisa Hegg1 and Colin Macphee3

1 GlaxoSmithKline, Cardiovascular Medicine Development Centre;
2 Worldwide Epidemiology; and
3 Center of Excellence for Drug Discovery, Philadelphia, PA.
4 Thomas Jefferson University, Philadelphia, PA.

aAddress correspondence to this author at: GlaxoSmithKline, 2301 Renaissance Blvd. RN0320, King of Prussia, PA 19406. E-mail andrew.2.zalewski{at}gsk.com.


Abstract

Background: Atherosclerosis is a systemic disease with focal rupture of vulnerable plaque responsible for major clinical events. Several population-based studies indicate an association between lipoprotein-associated phospholipase A2 (Lp-PLA2) and cardiovascular events. Lp-PLA2 is emerging as a biomarker that may be a potential link between oxidized LDL cholesterol and multifocal plaque vulnerability.

Content: Lp-PLA2 is produced by inflammatory cells of myeloid origin, is associated with circulating atherogenic lipoproteins (e.g., LDL), and is highly expressed in vulnerable plaques (de novo expression). Specificity of Lp-PLA2 toward polar phospholipids in oxidized LDL may contribute to the formation of downstream products (e.g., lysophosphatidylcholine and nonesterified fatty acids) that mediate processes intimately involved in plaque vulnerability in situ, including proinflammatory cell phenotype and macrophage death. Recent studies in patients with acute coronary syndrome (ACS) demonstrate that Lp-PLA2 and LDL measurements are not useful to assess the long-term cardiovascular risk shortly after the acute event, most likely because of the acute drop in LDL values that is commonly observed in ACS. However, when measured at later time points, Lp-PLA2 emerges as an independent predictor of the long-term cardiovascular risk, according to multivariate analysis.

Summary: Lp-PLA2 is an intriguing marker of cardiovascular risk and may also be a marker of plaque activity/vulnerability. Despite these findings, unanswered questions still exist with respect to this enzyme and its biologic role in atherosclerosis. Addressing these questions will help clarify the clinical utility of measuring Lp-PLA2 in routine clinical practice in the context of other approaches for identifying high-risk patients.




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