Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Oct 26, 2015; 7(10): 609-620
Published online Oct 26, 2015. doi: 10.4330/wjc.v7.i10.609
Lipoprotein-associated phospholipase A2 prognostic role in atherosclerotic complications
Giuseppe Maiolino, Valeria Bisogni, Giacomo Rossitto, Gian Paolo Rossi
Giuseppe Maiolino, Valeria Bisogni, Giacomo Rossitto, Gian Paolo Rossi, Department of Medicine - DIMED, Hypertension Clinic, University of Padua, 35128 Padova, Italy
Author contributions: All authors contributed to this paper.
Supported by FORICA (the FOundation for Advanced Research in Hypertension and Cardiovascular diseases, www.forica.it).
Conflict-of-interest statement: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Gian Paolo Rossi, MD, FACC, FAHA, Professor, Department of Medicine - DIMED, Hypertension Clinic, University of Padua, Via Giustiniani, 2, 35128 Padova, Italy. gianpaolo.rossi@unipd.it
Telephone: +39-049-8212279 Fax: +39-049-8217873
Received: February 24, 2015
Peer-review started: February 26, 2015
First decision: May 18, 2015
Revised: August 19, 2015
Accepted: September 25, 2015
Article in press: September 28, 2015
Published online: October 26, 2015
Processing time: 252 Days and 7.4 Hours
Abstract

Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque destabilization at a pre-clinical stage is, therefore, a major goal of cardiovascular research. Promising results along this line were provided by studies investigating the lipoprotein-associated phospholipase A2 (Lp-PLA2), a member of phospholipase A2 proteins family that plays a key role in the metabolism of pro-inflammatory phospholipids, as oxidized low-density lipoproteins, and in the generation of pro-atherogenic metabolites, including lysophosphatidylcholine and oxidized free fatty acids. We herein review the experimental and clinical studies supporting use of Lp-PLA2 activity for predicting cardiovascular events. To his end we considered not only Lp-PLA2 activity and mass, but also Lp-PLA2 gene variations and their association with incident coronary artery disease, stroke, and cardiovascular mortality. Based on these evidences the major scientific societies have included in their guidelines the measurement of Lp-PLA2 activity among the biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk. The results of two recently published major clinical trials with the Lp-PLA2 inhibitor darapladib, which seem to challenge the pathogenic role of Lp-PLA2, will also be discussed.

Keywords: Lipoprotein-associated phospholipase A2; Atherosclerosis; Coronary artery disease; Myocardial infarction; Prognosis

Core tip: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a promising new marker of atherosclerotic plaque destabilization, which plays a key role in the metabolism of pro-inflammatory phospholipids and in the generation of pro-atherogenic metabolites. This review focuses on the experimental and clinical studies supporting use of Lp-PLA2 for predicting cardiovascular events considering not only Lp-PLA2 activity and mass, but also Lp-PLA2 gene variations. Based on current evidences the major scientific societies have included Lp-PLA2 activity measurement in their guidelines among the biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk.