Electronegative LDL of FH subjects: Chemical characterization and induction of chemokine release from human endothelial cells

José Luis Sánchez-Quesada, Mercedes Camacho, Rosa Antón, Sonia Benítez, Lluis Vila, Jordi Ordóñez-Llanos

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85 Citations (Scopus)

Abstract

Electronegative LDL (LDL(-)) constitutes a plasma subfraction of LDL with proinflammatory properties. Its proportion is increased in familial hypercholesterolemia (FH); however, the characteristics of LDL(-) isolated from FH subjects have not been previously studied. In this work, the composition, oxidative status, and inflammatory capacity on endothelial cells of LDL(-) from FH and normolipemic (NL) subjects were evaluated. LDL(-) from FH was relatively enriched in esterified and free cholesterol and triglyceride, and had lower apoB and phospholipid content compared with the non-electronegative fraction (LDL(+)). LDL(-) also contained increased amounts of apoE, apoC-III, sialic acid, and non-esterified fatty acids (NEFAs). The same was observed in NL subjects, except that esterified cholesterol and phospholipid were similar in LDL(-) and LDL(+). No difference was observed between the two fractions concerning malondialdehyde, fatty acid hydroxides, and antioxidants, thereby indicating the absence of increased oxidation of LDL(-) compared with LDL(+). When LDL(-) (100 mg/l) from NL and FH subjects was incubated for 24 h with human umbilical vein endothelial cells (HUVECs), interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) increased twofold in the culture medium compared with LDL(+). Vascular cell adhesion molecule 1 (VCAM-1) expression was not increased by LDL(-). Our data indicate that LDL(-) from FH or NL subjects shows no evidence of increased oxidative modification compared to LDL(+); however, LDL(-) induces twofold the release of chemokines by endothelial cells. This effect, which may contribute to leukocyte recruitment and promote atherogenesis, may be greater in FH subjects in which LDL(-) can be up to eightfold higher than in NL subjects. © 2002 Elsevier Science Ireland Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)261-270
JournalAtherosclerosis
Volume166
Issue number2
DOIs
Publication statusPublished - 1 Feb 2003

Keywords

  • Electronegative LDL
  • Endothelial cells
  • Inflammation
  • Interleukin 8
  • Modified LDL
  • Monocyte chemotactic protein 1

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