High-density lipoproteins (HDL) possess atheroprotective properties including reverse cholesterol transport, antiinflammatory, antioxidant and antithrombotic properties. HDL are very heterogenous particles differing according to their density, size, form, charge, lipid and protein composition. In recent years, studies relative to HDL are not only focused on HDL-cholesterol level but also on the composition and functionality of HDL.
Type 2 diabetes (T2D) is associated with increased oxidative stress and cardiovascular complications. Chronic hyperglycemia results in protein glycation and oxidative stress, and consequently in glycoxidation of circulating lipoproteins. Atheroprotective properties of HDL are altered in addition to hypo-alphalipoproteinemia closely associated with metabolic syndrome.
Translational research studies of team 4 from CarMeN laboratory (Inserm U.1060/ Lyon 1 University, INRA U.1397, INSA-Lyon, Hospices Civils de Lyon) provide evidence for anti-aggregatory effects of glycoxidized HDL. Our results show that in vitro glycoxidized HDL and HDL isolated from plasma of T2D patients had increased concentrations of oxidized phospholipids derived from phospholipids esterified with linoleic acid, the main polyunsaturated fatty acid in HDL. These HDL dose-dependently inhibited collagen-induced platelet aggregation via SR-BI. Regarding the mechanism of action on platelet signaling pathways, glycoxidized HDL prevented collagen-induced increased phosphorylation of platelet p38 MAPK and cytosolic phospholipase A2, key enzymes involved in the release of arachidonic acid from membrane phospholipids. In addition, HDL enriched with oxidized phospholipids, namely PC (16:0/13-HODE), dose-dependently inhibited platelet aggregation, suggesting that some oxidized phospholipids could mediate the anti-aggregatory properties of glycoxidized HDL and T2D HDL.
In conclusion, our results show that HDL oxidation is not necessarily associated with deleterious effects and does not lead to the impairment of all their atheroprotective properties.
This study has been performed as part of the thesis of Quang Huy Lê. Our article has been selected by the Editors of Journal of Clinical Endocrinology and Metabolism : Best of JCEM 2015 in the subspeciality “Lipids”.
Lê QH, El Alaoui M, Véricel E, Ségrestin B, Soulère L, Guichardant M, Lagarde M, Moulin P, Calzada C. 2015. Glycoxidized HDL, HDL Enriched With Oxidized Phospholipids and HDL From Diabetic Patients Inhibit Platelet Function. J Clin Endocrinol Metab. 100(5):2006-2014. http://www.ncbi.nlm.nih.gov/pubmed/25794249
Lê QH, El Alaoui M, Véricel E, Ségrestin B, Soulère L, Guichardant M, Lagarde M, Moulin P, Calzada C. 2015. J Clin Endocrinol Metab. 100(5):2006-2014. Pubmed