6533b855fe1ef96bd12aff2b

RESEARCH PRODUCT

Specific enrichment of 2-arachidonoyl-lysophosphatidylcholine in carotid atheroma plaque from type 2 diabetic patients

Damien DenimalAnne AthiasNicolas AbelloDavid MassonLaurent LagrostJean-michel PetitJean-paul Pais De BarrosLaurent MartinBenjamin KretzCaroline TruntzerLouise MénégautPatrick DucoroyEric Steinmetz

subject

Male0301 basic medicineEndothelial lipasePathologymedicine.medical_treatmentCoronary Artery DiseaseCarotid endarterectomy030204 cardiovascular system & hematologyCohort StudiesCoronary artery diseasechemistry.chemical_compound0302 clinical medicineEndarterectomy CarotidLysophosphatidylcholineDiabetesMiddle Aged[ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular systemPrognosisLipidsPlaque Atherosclerotic3. Good healthStrokeCholesterolArachidonic acidCholesteryl esterFemalelipids (amino acids peptides and proteins)Arachidonic acidCardiology and Cardiovascular Medicinemedicine.medical_specialtyContext (language use)Biology03 medical and health sciences[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular systemDiabetes mellitusInternal medicinemedicineHumansAgedLysophosphatidylcholinesLipaseAtherosclerosismedicine.disease030104 developmental biologyAtheromaEndocrinologyDiabetes Mellitus Type 2chemistryMultivariate AnalysisEicosanoids

description

IF 3.942; International audience; Background and aims: 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.Methods: 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.Results: 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.Conclusions: 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

https://doi.org/10.1016/j.atherosclerosis.2016.05.004