Wide proinflammatory effect of electronegative low-density lipoprotein on human endothelial cells assayed by a protein array

Sònia Benítez, Mercedes Camacho, Cristina Bancells, Luis Vila, José Luis Sánchez-Quesada, Jordi Ordóñez-Llanos

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44 Citations (Scopus)


Electronegative low-density lipoprotein (LDL(-)) is a modified subfraction of LDL present in plasma able to induce the release of interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) by human umbilical vein endothelial cells (HUVEC). To ascertain whether further inflammation mediator release could be induced by LDL(-), a protein array system was used to measure 42 cytokines and related compounds. Native LDL and LDL(-) isolated from normolipemic subjects were incubated for 24 h with HUVEC and culture supernatants were used to measure inflammation mediator release. The protein array revealed that IL-6, granulocyte/monocyte colony-stimulating factor (GM-CSF) and growth-related oncogene (GRO) release were increased by cultured HUVEC in response to LDL(-). LDL(-) enhanced production of IL-6 (4-fold vs. LDL(+)), GM-CSF (4-fold), GROβ (2-fold) and GROγ (7-fold) was confirmed by ELISA. Time-course experiments revealed that IL-6 was released earlier than the other inflammation mediators, suggesting a first-wave cytokine action. However, the addition of IL-6 alone did not stimulate the production of IL-8, MCP-1 or GM-CSF. Moreover, IL-8, MCP-1 or GM-CSF alone did not promote the release of the other inflammatory molecules. Modification of LDL(+) by phospholipase A2-mediated lipolysis or by loading with non-esterified fatty acids (NEFA) reproduced the action of LDL(-), thereby suggesting the involvement of NEFA and/or lysophosphatidylcholine in the release of these molecules. Our results indicate that LDL(-) promotes a proinflammatory phenotype in endothelial cells through the production of cytokines, chemokines and growth factors. © 2006 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)1014-1021
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Publication statusPublished - 1 Sep 2006


  • Electronegative LDL
  • GRO
  • Granulocyte/monocyte colony-stimulating factor
  • Inflammation
  • Interleukin 6


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