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

Abstract

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.

Plasma/Serum Plasmalogens

“…Plasma/serum Pls appear to be associated with diverse clinical manifestations including metabolic diseases associated with oxidative stress and chronic inflammation [50][51][52][53][54]. Thus, plasma/serum Pls may be potentially useful biomarkers for these conditions.…”

Serum choline plasmalogens, particularly those with oleic acid in sn-2, are associated with proatherogenic state

“…Oxidative stress may also be associated with T2D and related cardiovascular diseases. Notably, decreased PlsEtn levels and increased lipid peroxidation were found in LDL particles from obese patients with metabolic syndrome (MetS) and patients with T2D ( 8 ), which may be a risk factor for atherosclerosis. Plasma Pls may be a good marker for inferring the level of oxidative stress and predicting cardiovascular mortality in patients with end-stage renal disease ( 9 ).…”

Oxidized LDL activates blood platelets through CD36/NOX2–mediated inhibition of the cGMP/protein kinase G signaling cascade

“…One major factor that contributes to platelet hyperactivity in CVD is dyslipidemia, [2][3][4] which is characterized by the accumulation of oxidized lipids in the circulation and vessel walls, primarily in the form of oxidized low-density lipoproteins (oxLDLs). The accumulation of oxidized lipids in the plasma of high-risk patients is associated with increased platelet reactivity, 5 whereas oxLDLs, both generated in vitro and isolated from subjects with CVD, contribute to platelet activation, suggesting that they are potential causative agents for the promotion of platelet hyperactivity in CVD. [6][7][8][9][10][11][12] However, given the heterogeneous nature of oxLDLs, the mechanisms by which they promote platelet activity and thrombosis in vivo are likely to be numerous.…”