Atherogenic and inflammatory profile of human arterial endothelial cells (HUAEC) in response to LDL subfractions

Background: Electronegative LDL (LDL(-)) is a minor modified LDL fraction present in plasma that has been demonstrated to be inflammatory in endothelial cells isolated from human umbilical vein (HUVEC). Methods: A protein array able to measure 42 cytokines, chemokines and related compounds involved in atherogenesis was used to determine their release into the culture medium of human arterial endothelial cells (HUAEC) activated or not by two low-density lipoprotein (LDL) fractions isolated from human plasma by anion-exchange chromatography. Results: The results of the protein array (confirmed using specific ELISAs for each induced factor) revealed that HUAEC in the absence of stimuli released small amounts of interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1) and growth-related oncogene (GRO). The major native LDL fraction (named LDL(+)) increased the release of these molecules and also those of interleukin 6 (IL-6) and GRO alpha. Compared to LDL(+), the minor modified fraction, named electronegative LDL (LDL(-)), increased all these factors to a greater degree and also induced the release of granulocyte-monocyte colony-stimulating factor (GM-CSF) and platelet-derived growth factor B (PDGF-B). These results were confirmed by ELISA. Conclusions: All these results indicate that, compared to LDL(+), LDL(-) fraction promotes not only the release of proinflammatory factors but also those of atherogenic factors in endothelial cells of arterial origin, thereby suggesting a new role for LDL(-) in atherogenesis. (c) 2006 Elsevier B.V. All rights reserved.