title: Specific enrichment of 2-arachidonoyl-lysophosphatidylcholine in carotid atheroma plaque from type 2 diabetic patients.
abstract: Diabetic patients are at high risk of stroke and coronary artery disease. Recent data suggest that arachidonic acid metabolism is altered in diabetic conditions and that these alterations contribute to accelerated atherosclerosis. Little is known about how these alterations affect the metabolism and the proportions of different lipid species within the atherosclerotic plaque. The aim of our study was to perform a targeted lipidomic analysis of human atherosclerotic lesions, with a specific focus on PUFA-containing lipid species, to reveal differences in the fatty-acid composition of plaque in diabetic patients compared with non-diabetic controls.
  
  
  
  Carotid atheroma plaque samples were obtained from 31 diabetic and 48 non-diabetic patients undergoing carotid endarterectomy. Targeted lipidomic analysis was then performed to determine the fatty acid composition of major glycerophospholipids and cholesteryl ester species by liquid chromatography-tandem mass spectrometry.
  
  
  
  Atheroma plaques from diabetic patients were significantly enriched with 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) (2.3 ± 0.8% Vs. 1.8 ± 0.6% p = 0.0002). Multivariable logistic regression showed that an increased 2-AA-LPC level was independently associated with diabetes. Finally, a positive relationship was found between 2-AA-LPC and HbA1c levels. Interestingly, endothelial lipase and calcium independent PLA2 gamma which could account for the production of 2-AA-LPC were detected in carotid plaques by immunohistochemistry.
  
  
  
  2-AA-LPC stands at the crossroads of major metabolic pathways that lead to the synthesis of bioactive molecules such as AA-derived eicosanoids, 2-AA-lysophosphatidic acid and 2-AA-glycerol. 2-AA-LPC therefore appears to be a promising molecule to investigate in the context of diabetes.
authors.affiliation: Centre de Recherche Inserm-UMR866, Faculté de Médecine, Université de Bourgogne, 21079, Dijon, France; Centre Hospitalier Universitaire Dijon, Hôpital du Bocage, 21034, Dijon, France.
authors.forename: Louise
authors.initials: L
authors.lastname: Ménégaut
authors.affiliation: Centre de Recherche Inserm-UMR866, Faculté de Médecine, Université de Bourgogne, 21079, Dijon, France; Centre Hospitalier Universitaire Dijon, Hôpital du Bocage, 21034, Dijon, France. Electronic address: david.masson@chu-dijon.fr.
authors.forename: David
authors.initials: D
authors.lastname: Masson
authors.affiliation: Centre Hospitalier Universitaire Dijon, Hôpital du Bocage, 21034, Dijon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Abello
authors.affiliation: Centre de Recherche Inserm-UMR866, Faculté de Médecine, Université de Bourgogne, 21079, Dijon, France; Centre Hospitalier Universitaire Dijon, Hôpital du Bocage, 21034, Dijon, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Denimal
authors.affiliation: Clinical Innovation Proteomic Platform - CLIPP, Pôle de Recherche Université de Bourgogne, 21000, Dijon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Truntzer
authors.affiliation: Clinical Innovation Proteomic Platform - CLIPP, Pôle de Recherche Université de Bourgogne, 21000, Dijon, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ducoroy
authors.affiliation: Centre de Recherche Inserm-UMR866, Faculté de Médecine, Université de Bourgogne, 21079, Dijon, France; Centre Hospitalier Universitaire Dijon, Hôpital du Bocage, 21034, Dijon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
authors.affiliation: Centre de Recherche Inserm-UMR866, Faculté de Médecine, Université de Bourgogne, 21079, Dijon, France; Lipidomic Analytical Platform, Université de Bourgogne, 15 Bd De Lattre de Tassigny, Dijon, France.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Pais de Barros
authors.affiliation: Lipidomic Analytical Platform, Université de Bourgogne, 15 Bd De Lattre de Tassigny, Dijon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Athias
authors.affiliation: Centre de Recherche Inserm-UMR866, Faculté de Médecine, Université de Bourgogne, 21079, Dijon, France; Centre Hospitalier Universitaire Dijon, Hôpital du Bocage, 21034, Dijon, France.
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Petit
authors.affiliation: Centre Hospitalier Universitaire Dijon, Hôpital du Bocage, 21034, Dijon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Martin
authors.affiliation: Centre de Recherche Inserm-UMR866, Faculté de Médecine, Université de Bourgogne, 21079, Dijon, France; Centre Hospitalier Universitaire Dijon, Hôpital du Bocage, 21034, Dijon, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Steinmetz
authors.affiliation: Centre Hospitalier Universitaire Dijon, Hôpital du Bocage, 21034, Dijon, France; CRB Ferdinand Cabanne BB-0033-00044, France; Centre Hospitalier Louis Pasteur, Colmar, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kretz
mesh_terms: D000368:Aged; D016718:Arachidonic Acid / Q000737:chemistry*; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000473:pathology*; D015777:Eicosanoids; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D008049:Lipase / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008244:Lysophosphatidylcholines / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000473:pathology*; D011379:Prognosis; D020521:Stroke / Q000150:complications
chemical_list: D015777:Eicosanoids; D008055:Lipids; D008244:Lysophosphatidylcholines; D016718:Arachidonic Acid; D002784:Cholesterol; D008049:Lipase
keywords: Arachidonic acid; Atherosclerosis; Diabetes; Lysophosphatidylcholine