PMID- 37710315 OWN - NLM STAT- MEDLINE DCOM- 20230918 LR - 20231123 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 22 IP - 1 DP - 2023 Sep 14 TI - Inflammation and oxidative stress markers in type 2 diabetes patients with Advanced Carotid atherosclerosis. PG - 248 LID - 10.1186/s12933-023-01979-1 [doi] LID - 248 AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major global health issue and a significant risk factor for atherosclerosis. Atherosclerosis in T2DM patients has been associated with inflammation, insulin resistance, hyperglycemia, dyslipidemia, and oxidative stress. Identifying molecular features of atherosclerotic plaques in T2DM patients could provide valuable insights into the pathogenesis of the disease. METHODS: The MASCADI (Arachidonic Acid Metabolism in Carotid Stenosis Plaque in Diabetic Patients) study aimed to investigate the increase of 2-arachidonoyl-lysophatidylcholine (2-AA-LPC) in carotid plaques from T2DM and control patients and to explore its association with plaque vulnerability as well as with blood and intra-plaque biomarkers altered during diabetes. RESULTS: In a population of elderly, polymedicated patients with advanced stage of atherosclerosis, we found that T2DM patients had higher systemic inflammation markers, such as high-sensitivity C-reactive protein (hsCRP) and IL-1beta, higher levels of oxysterols, increased triglyceride levels, and decreased HDL levels as compared to control patients. Furthermore, 2-AA-LPC was significantly enriched in plaques from diabetic patients, suggesting its potential role in diabetic atherosclerosis. Interestingly, 2-AA-LPC was not associated with systemic markers related to diabetes, such as hsCRP, triglycerides, or HDL cholesterol. However, it was significantly correlated with the levels of inflammatory markers within the plaques such as lysophospholipids and 25-hydroxycholesterol, strengthening the link between local inflammation, arachidonic acid metabolism and diabetes. CONCLUSION: Our study is in line with a key role for inflammation in the pathogenesis of diabetic atherosclerosis and highlights the involvement of 2-AA-LPC. Further research is needed to better understand the local processes involved in the alteration of plaque composition in T2DM and to identify potential therapeutic targets. TRIAL REGISTRATION: The MASCADI was registered on ClinicalTrials.gov (clinical registration number: NCT03202823). CI - (c) 2023. BioMed Central Ltd., part of Springer Nature. FAU - Menegaut, Louise AU - Menegaut L AD - Universite Bourgogne, LNC UMR1231, Dijon, France. AD - INSERM, UMR1231, Dijon, France. AD - Universite Bourgogne-Franche Comte, LipSTIC LabEx, Dijon, France. AD - CHU Dijon, Laboratory of Clinical Chemistry, Dijon, France. FAU - Laubriet, Aline AU - Laubriet A AD - Department of Cardiovascular and Thoracic Surgery, CHU Dijon, Dijon, France. FAU - Crespy, Valentin AU - Crespy V AD - Department of Cardiovascular and Thoracic Surgery, CHU Dijon, Dijon, France. FAU - Leleu, Damien AU - Leleu D AD - Universite Bourgogne, LNC UMR1231, Dijon, France. AD - INSERM, UMR1231, Dijon, France. AD - Universite Bourgogne-Franche Comte, LipSTIC LabEx, Dijon, France. AD - CHU Dijon, Laboratory of Clinical Chemistry, Dijon, France. FAU - Pilot, Thomas AU - Pilot T AD - Universite Bourgogne, LNC UMR1231, Dijon, France. AD - INSERM, UMR1231, Dijon, France. AD - Universite Bourgogne-Franche Comte, LipSTIC LabEx, Dijon, France. FAU - Van Dongen, Kevin AU - Van Dongen K AD - Universite Bourgogne, LNC UMR1231, Dijon, France. AD - INSERM, UMR1231, Dijon, France. AD - Universite Bourgogne-Franche Comte, LipSTIC LabEx, Dijon, France. FAU - de Barros, Jean-Paul Pais AU - de Barros JP AD - Universite Bourgogne, LNC UMR1231, Dijon, France. AD - INSERM, UMR1231, Dijon, France. AD - Universite Bourgogne-Franche Comte, LipSTIC LabEx, Dijon, France. AD - Lipidomic Analytic Platform, Universite Bourgogne Franche-Comte, Dijon, France. FAU - Gautier, Thomas AU - Gautier T AD - Universite Bourgogne, LNC UMR1231, Dijon, France. AD - INSERM, UMR1231, Dijon, France. AD - Universite Bourgogne-Franche Comte, LipSTIC LabEx, Dijon, France. FAU - Petit, Jean-Michel AU - Petit JM AD - Universite Bourgogne, LNC UMR1231, Dijon, France. AD - INSERM, UMR1231, Dijon, France. AD - Universite Bourgogne-Franche Comte, LipSTIC LabEx, Dijon, France. AD - Department of Endocrinology and metabolic diseases, CHU Dijon, Dijon, France. FAU - Thomas, Charles AU - Thomas C AD - Universite Bourgogne, LNC UMR1231, Dijon, France. AD - INSERM, UMR1231, Dijon, France. AD - Universite Bourgogne-Franche Comte, LipSTIC LabEx, Dijon, France. FAU - Nguyen, Maxime AU - Nguyen M AD - Universite Bourgogne, LNC UMR1231, Dijon, France. AD - INSERM, UMR1231, Dijon, France. AD - Universite Bourgogne-Franche Comte, LipSTIC LabEx, Dijon, France. AD - CHU Dijon Department of Anesthesiology and Intensive Care, Dijon, France. FAU - Steinmetz, Eric AU - Steinmetz E AD - Department of Cardiovascular and Thoracic Surgery, CHU Dijon, Dijon, France. FAU - Masson, David AU - Masson D AD - Universite Bourgogne, LNC UMR1231, Dijon, France. David.masson@chu-dijon.fr. AD - INSERM, UMR1231, Dijon, France. David.masson@chu-dijon.fr. AD - Universite Bourgogne-Franche Comte, LipSTIC LabEx, Dijon, France. David.masson@chu-dijon.fr. AD - CHU Dijon, Laboratory of Clinical Chemistry, Dijon, France. David.masson@chu-dijon.fr. AD - UFR des sciences de sante, Bvd Jeanne d'Arc, Dijon, 21000, France. David.masson@chu-dijon.fr. LA - eng SI - ClinicalTrials.gov/NCT03202823 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230914 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 9007-41-4 (C-Reactive Protein) RN - 27YG812J1I (Arachidonic Acid) SB - IM MH - Aged MH - Humans MH - *Diabetes Mellitus, Type 2/complications/diagnosis/epidemiology MH - C-Reactive Protein MH - Arachidonic Acid MH - *Carotid Artery Diseases/diagnostic imaging/epidemiology MH - *Plaque, Atherosclerotic MH - Inflammation/diagnosis MH - *Atherosclerosis PMC - PMC10503074 OTO - NOTNLM OT - Arachidonic acid OT - Atherosclerosis OT - Carotid OT - Diabetes OT - Inflammation COIS- The authors have no conflict of interest to disclose. EDAT- 2023/09/15 00:42 MHDA- 2023/09/18 12:42 PMCR- 2023/09/14 CRDT- 2023/09/14 23:49 PHST- 2023/07/17 00:00 [received] PHST- 2023/09/03 00:00 [accepted] PHST- 2023/09/18 12:42 [medline] PHST- 2023/09/15 00:42 [pubmed] PHST- 2023/09/14 23:49 [entrez] PHST- 2023/09/14 00:00 [pmc-release] AID - 10.1186/s12933-023-01979-1 [pii] AID - 1979 [pii] AID - 10.1186/s12933-023-01979-1 [doi] PST - epublish SO - Cardiovasc Diabetol. 2023 Sep 14;22(1):248. doi: 10.1186/s12933-023-01979-1.