Impaired fluidity and oxidizability of HDL hydrophobic core and amphipathic surface in dyslipidemic men Roberta Cazzola a, ⁎ , Erica Cassani b , Michela Barichella b , Benvenuto Cestaro a a Department of Biomedical and Clinical Sciences “L. Sacco”-Faculty of Medicine and Surgery-University of Milan, Via G. B. Grassi, 74 – 20157 Milan, Italy b Parkinson Institute, Istituti Clinici di Perfezionamento (ICP), Milan ARTICLE INFO ABSTRACT Article history: Received 24 September 2012 Accepted 11 January 2013 Objective. To examine and compare the composition, fluidity and oxidizability of HDL hydrophobic core and amphipathic surface of two groups of adult males (25 kg/ m 2 <BMI<30 kg/m 2 ), the former mixed dyslipidemic patients (MD) and the latter age- and BMI-matched healthy controls. Methods and results. Pyrenyl-cholesteryl ester and pyrenyl-phosphatidylcholine, respectively incorporated in HDL core or surface were used for measuring both 2,2'- azobis-2-methyl-propanimidamide-dihydrochloride-induced peroxidation kinetics and fluidities of these regions. In comparison with the controls, MD HDL showed: a) higher free cholesterol to phospholipid ratio in surface and triacylglycerols to cholesteryl ester ratio in the core, b) higher malondialdehyde levels and lower alpha-tocopherol and beta-carotene to neutral lipid ratios, c) a more rigid surface and more fluid core, d) dramatically decreased lag-time and increased propagation rate of peroxidation kinetic in the core, but only an increased propagation rate on the surface. Conclusion. These results suggest that better knowledge of the physical–chemical properties and oxidizability of HDL core and surface could contribute to better understanding of the mechanisms connecting HDL alteration to increased risk of CDV in MD. © 2013 Elsevier Inc. All rights reserved. Keywords: Mixed dyslipidemia HDL function Lipid peroxidation 1. Introduction HDLs have been shown to exert a wide spectrum of anti- atherogenic activities, including the promotion of reverse cholesterol transport, anti-inflammatory actions in vascula- ture [1] and protection of LDL against oxidation [2]. Moreover, the capacity of HDL to accumulate [3,4] and neutralize [5] or transport oxidized lipids to the liver [6] suggests a role of HDL in the detoxification of these molecules in vivo. Recent evidence suggests that structural modification and composition alter- ation of HDL due to chronic inflammation and acute phase responses may result in loss of normal biological function of these lipoproteins [1,7]. Further, changes in lipid composition associated with some forms of dyslipidemia, such as hyper- cholesterolemia and hypertriacylglycerolemia, have been shown to influence the anti-atherogenic capacity of HDL [1]. In the western world, one of the most common forms of dyslipidemia is mixed dyslipidemia (MD) featuring elevated METABOLISM CLINICAL AND EXPERIMENTAL 62 (2013) 986 – 991 Abbreviations: AAPH, 2,2′-azobis(2-methylpropionamidine) dihydrochloride; BMI, body mass index; CE, cholesteryl esters; CETP, cholesterol ester transfer protein; CRP, C-reactive protein, CVD, cardiovascular diseases; DTPA, diethylene triamine pentaacetic acid; HOMA-IR, homeostatic model of assessment for insulin resistance; LCAT, lecithin-cholesterol acyltransferase; LOOH, lipid peroxides; MDA, malondialdehyde; MD, mixed dyslipidemia; PyrPC, decanoyl γ-palmitoyl L-α phosphatidylcholine; PyrCE, cholesteryl (pyren-1-yl) hexanoate; PON, Paraoxonase; PUFA, polyunsaturated fatty acids; PL, phospholipids; TAG, triacylglycerols. ⁎ Corresponding author. Tel.: +39 0250319690; fax: +39 0250319697. E-mail address: roberta.cazzola@unimi.it (R. Cazzola). 0026-0495/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.metabol.2013.01.012 Available online at www.sciencedirect.com Metabolism www.metabolismjournal.com