[Lp-PLA2, a biomarker of vascular inflammation and vulnerability of atherosclerosis plaques].
A chronic inflammation is involved in various stages of development of the atherosclerotic plaques. Among the emerging biomarkers of atherogenesis, the lipoprotein-associated phospholipase A2 (Lp-PLA2), formerly known as PAF-acetylhydrolase (McIntyre et al., 2009), hydrolyses the oxidized short chain phospholipids of low-density lipoproteins (LDL), thereby releasing pro-inflammatory mediators (lysophospholipids and oxidized fatty acids). Lp-PLA2, produced by monocytes/macrophages and T-lymphocytes, and mainly associated with LDL (Gazi et al., 2005), is predominantly expressed in the necrotic center of the atherosclerotic plaques and in the macrophage-rich areas (Kolodgie et al., 2006). It would have a predictive role of cardiovascular (CV) events in relation to the vulnerability of atherosclerotic plaques. Determination of Lp-PLA2 has been proposed in the assessment of the CV risk, to ensure a better stratification of populations at intermediate risk for targeted therapy (Davidson et al., 2008). Its proatherogenic role suggested that inhibition of its activity could ensure a better vascular protection in combination with cholesterol-lowering agents. Nevertheless, Lp-PLA2 is not yet a fully validated marker for use in daily clinical practice, especially since the studies using an inhibitor of Lp-PLA2 (darapladib) (STABILITY Investigators et al., 2014; O'Donoghue et al., 2014) did not show any reduction in coronary events. Lp-PLA2 could have a site-specific role in plaque inflammation and development (Fenning et al., 2015). High Lp-PLA2 activity could reflect a response to pro-inflammatory stress characteristic of atherosclerosis (Marathe et al., 2014). This presentation aims at clarifying the involvement of Lp-PLA2 in the pathophysiology of atherosclerosis, and at assessing its interest both as a biomarker for the onset of CV events and as a therapeutic target.
Service de biochimie métabolique, hôpitaux universitaires Pitié-Salpêtrière-Charles-Foix, AP-HP, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France; Unité pédagogique de biochimie, faculté des sciences pharmaceutiques et biologiques, université Paris Descartes, Sorbonne Paris Cité, 4, avenue de l'Observatoire, 75006 Paris, France; Inserm UMR_S 1166 ICAN, université Pierre-et-Marie-Curie, hôpital de La Pitié, bâtiment Benjamin-Delessert, 83, boulevard de l'Hôpital, 75651 Paris cedex 13, France. Electronic address: dominique.rousselot@aphp.fr.
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Bonnefont-Rousselot
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D006801:Humans; D058226:Plaque, Atherosclerotic / Q000097:blood*; D014657:Vasculitis / Q000097:blood*
D015415:Biomarkers; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human
Atherogenesis; Athérogenèse; Biomarker; Biomarqueur; Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)); Phospholipase A(2) associée aux lipoprotéines (Lp-PLA(2))