Poor glycemic control in type 2 diabetes enhances functional and compositional alterations of small, dense HDL3c

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• 作者：Leonardo Gomez Rosso^a ; ^b ; ^c ; Marie Lhomme^d ; Tomas Meroñ ; o^c ; Ana Dellepiane^e ; Patricia Sorroche^f ; Lyamine Hedjazi^d ; ^e ; Emile Zakiev^a ; ^b ; ^g ; Vasily Sukhorukov^a ; ^b ; ^g ; Alexander Orekhov^g ; ^h ; Julieta Gasparri^c ; M. John Chapman^a ; ^b ; Fernando Brites^c ; Anatol Kontush^a ; ^b ; ^{anatol.kontush@upmc.fr}
• 关键词：ANOVA ; analysis of variance ; ApoAI ; apolipoprotein A-I ; ApoA-II ; apolipoprotein A-II ; ApoB ; apolipoprotein B ; BMI ; Body Mass Index ; CVD ; cardiovascular disease ; CE ; cholesteryl ester ; Cer ; ceramide ; CETP ; cholesteryl ester transfer protein ; EDTA ; ethylene diamine tetra acetic acid ; EGF ; endothelial growth factor ; FC ; free cholesterol ; HbA1c ; glycated hemoglobin ; HDL ; high-density lipoprotein ; HDL-C ; HDL-cholesterol ; HsCRP ; High-Sensitive C-Reactive Protein ; ICAM-1 ; intercellular cell adhesion m
• 刊名：Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：1862
• 期：2
• 页码：188-195
• 全文大小：413 K
• 卷排序：1862

文摘

High-density lipoprotein (HDL) possesses multiple biological activities; small, dense HDL3c particles displaying distinct lipidomic composition exert potent antiatherogenic activities which can be compromised in dyslipidemic, hyperglycemic insulin-resistant states. However, it remains indeterminate (i) whether such functional HDL deficiency is related to altered HDL composition, and (ii) whether it originates from atherogenic dyslipidemia, dysglycemia, or both.In the present work we analyzed compositional characteristics of HDL subpopulations and functional activity of small, dense HDL3c particles in treatment-naïve patients with well-controlled (n = 10) and poorly-controlled (n = 8) type 2 diabetes (T2D) and in normolipidemic age- and sex-matched controls (n = 11).Our data reveal that patients with both well- and poorly-controlled T2D displayed dyslipidemia and low-grade inflammation associated with altered HDL composition. Such compositional alterations in small, dense HDL subfractions were specifically correlated with plasma HbA1c levels. Further analysis using a lipidomic approach revealed that small, dense HDL3c particles from T2D patients with poor glycemic control displayed additional modifications of their chemical composition. In parallel, antioxidative activity of HDL3c towards oxidation of low-density lipoprotein was diminished.These findings indicate that defective functionality of small, dense HDL particles in patients with T2D is not only affected by the presence of atherogenic dyslipidemia, but also by the level of glycemic control, reflecting compositional alterations of HDL.