LDL from obese patients with the metabolic syndrome show increased lipid peroxidation and activate platelets

• Published in: Diabetologia 2011-11, Vol.54 (11), p.2931-2940
• Main Authors: Colas, R., Sassolas, A., Guichardant, M., Cugnet-Anceau, C., Moret, M., Moulin, P., Lagarde, M., Calzada, C.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Arachidonic Acid - metabolism; Atherosclerosis; Biological and medical sciences; Biomarkers - blood; Blood platelets; Blood Platelets - enzymology; Blood Platelets - metabolism; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty acids; Human Physiology; Humans; Internal Medicine; Kinases; Lipid Peroxidation; Lipids; Lipids - blood; Lipoproteins, LDL - blood; Lipoproteins, LDL - chemistry; Lipoproteins, LDL - metabolism; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic syndrome; Metabolic Syndrome - complications; Middle Aged; Miscellaneous; Obesity; Obesity - blood; Obesity - complications; Obesity - metabolism; Other metabolic disorders; Oxidation; Oxidative Stress; Phospholipases A2, Secretory - blood; Phospholipases A2, Secretory - metabolism; Phosphorylation; Plasma; Platelet Activation; Proteins; Signal Transduction
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-011-2272-8

Aims/hypothesis This study assessed oxidative stress in LDL from obese patients with the metabolic syndrome and compared it with that in LDL from type 2 diabetic patients or control volunteers. It also determined the effect on platelets of LDL from the three groups. Methods The profiles of lipids, fatty acids and fatty acid oxidation products were determined in LDL isolated from plasma of patients with the metabolic syndrome, patients with type 2 diabetes and volunteers ( n  = 10 per group). The effects of LDL from the participant groups on the platelet arachidonic acid signalling cascade and aggregation were investigated. Results Compared with LDL from control volunteers, LDL from obese metabolic syndrome and type 2 diabetic patients had lower cholesteryl ester, higher triacylglycerol and lower ethanolamine plasmalogen levels. Proportions of linoleic acid were decreased in phosphatidylcholine and cholesteryl esters in LDL from both patient groups. Among the markers of lipid peroxidation, oxidation products of linoleic acid (hydroxy-octadecadienoic acids) and malondialdehyde were increased by 59% and twofold, respectively in LDL from metabolic syndrome and type 2 diabetic patients. LDL from metabolic syndrome and type 2 diabetic patients were equally potent in activating the platelet arachidonic acid signalling cascade through increased phosphorylation of p38 mitogen-activated protein kinase and cytosolic phospholipase A 2 , and through increased thromboxane B 2 formation. LDL from patients with the metabolic syndrome and type 2 diabetes potentiated platelet aggregation by threefold and 3.5-fold respectively, whereas control LDL had no activating effects on platelets. Conclusions/interpretation The metabolic syndrome in obese patients, without or with diabetes, is associated with increased oxidative stress in LDL, which triggers platelet activation. Trial registration: ClinicalTrials.gov NCT00932087 Funding: The study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and ANR (Agence Nationale de la Recherche).