Electronegative low-density lipoprotein subfraction from type 2 diabetic subjects is proatherogenic and unrelated to glycemic control

Sónia Benítez, Antonio Pérez, José Luis Sánchez-Quesada, Ana María Wagner, Mercedes Rigla, Rosa Arcelus, Óscar Jorba, Jordi Ordóñez-Llanos

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19 Citations (Scopus)

Abstract

Background: The physicochemical and biological characteristics of electronegative low-density lipoprotein (LDL) (LDL(-)) from type 2 diabetic patients (DM2), before and after insulin therapy, were studied. Methods: Total LDL was subfractionated in LDL(+) (native LDL) and LDL(-) by anion-exchange chromatography. Results: The proportion of LDL(-) was increased in plasma from DM2 patients compared to control subjects (13.8 ± 4.6% versus 6.1 ± 2.5, P < 0.05) and was not modified after glycemic optimization (14.0 ± 5.9%). LDL(-) from DM2 patients presented similar differential characteristics versus LDL(+) than LDL(-) from controls; that is, decreased apoB and oxidizability, and increased triglyceride, nonesterified fatty acids (NEFA), apoE, apoC-III, platelet-activating factor (PAF) acetylhydrolase activity and aggregability. No difference in particle size, antioxidants, malondialdehyde (MDA), fructosamine or glycated low-density lipoprotein (gLDL) was observed between LDL subfractions. Concerning differences between LDL subfractions isolated from DM2 and from control subjects, the former showed increased MDA, fructosamine and gLDL proportion and decreased LDL size and antioxidant content. The only effect of glycemic optimization was a decrease in fructosamine and gLDL in LDL(+) from DM2 subjects. LDL(-) from DM2 patients presented low binding affinity to the low-density lipoprotein receptor (LDLr) in cultured fibroblasts compared to LDL(+) and two- to threefold increased ability to release interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in endothelial cells. Conclusion: These results suggest that, although nonenzymatic glycosylation and oxidation are increased in type 2 diabetes, these features would not be directly involved in the generation of LDL(-). Moreover, LDL(-) properties suggest that the high proportion observed in plasma could promote accelerated atherosclerosis in DM2 patients through increased residence time in plasma and induction of inflammatory responses in artery wall cells. Copyright © 2006 John Wiley & Sons, Ltd.
Original languageEnglish
Pages (from-to)26-34
JournalDiabetes/Metabolism Research and Reviews
Volume23
Issue number1
DOIs
Publication statusPublished - 1 Jan 2007

Keywords

  • Atherosclerosis
  • Electronegative low-density lipoprotein
  • Inflammation
  • Type 2 diabetes mellitus

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