Increased lysophosphatidylcholine and non-esterified fatty acid content in LDL induces chemokine release in endothelial cells : Relationship with electronegative LDL
Benitez, Sonia (Institut d'Investigació Biomèdica Sant Pau)
Camacho, Mercedes (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Arcelus, Rosa (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Vila, Luis (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Bancells, Cristina (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Ordóñez, J. (Jordi) 1952- (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Sanchez-Quesada, Jose Luis (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))

Data:	2004
Resum:	Electronegative low-density lipoprotein (LDL(-)) is a plasma-circulating LDL subfraction with proinflammatory properties that induces the production of chemokines in cultured endothelial cells. However, the specific mechanism of LDL(-)-mediated chemokine release is presently unknown. A characteristic feature of LDL(-) is an increased content of lysophosphatidylcholine (LPC) and non-esterified fatty acids (NEFA). The effect of increasing amounts of LPC and NEFA associated with LDL on the release of chemokines by endothelial cells was studied. Total LDL was subfractionated by anion-exchange chromatography in electropositive (LDL(+)) and LDL(-). LDL(-) contained two-fold more LPC and NEFA than LDL(+) and induced two- to four-fold more (p < 0. 05) interleukin-8 (IL-8, 11. 5 ± 8. 2 ng/10 cells) and monocyte chemotactic protein-1 (MCP-1, 10. 8 ± 3. 8 ng/10 cells) release by human umbilical vein endothelial cells (HUVEC) than LDL(+) (IL-8: 3. 4 ± 1. 5 ng/10 cells, MCP-1: 5. 8 ± 2. 9 ng/10 cells). The content of LPC and NEFA in LDL(+) was increased by enzymatic treatment with secretory phospholipase A (sPLA ) at 5 ng/mL or 20 ng/mL or by incubation with NEFA at 2 mmol/L. Modification of LDL(+) by both methods did not result in oxidative modification as demonstrated by the lack of change in antioxidants, conjugated dienes and malondialdehyde content. sPLA treatment resulted in an increase in LPC and NEFA in LDL(+) which enhanced its ability to release IL-8 and MCP-1 by HUVEC in a concentration-dependent manner (sPLA (5)-LDL; IL-8: 7. 1 ± 3. 8 ng/10 cells, MCP-1: 8. 0 ± 5. 1 ng/10 cells; sPLA (20)-LDL; IL-8: 20. 8 ± 11. 2 ng/10 cells, MCP-1: 15. 0 ± 7. 5 ng/10 cells). NEFA loading of LDL(+) also favored the release of IL-8 and MCP-1 (IL-8: 7. 8 ± 6. 1 ng/10 cells, MCP-1: 8. 4 ± 2. 7 ng/10 cells, p < 0. 05 versus LDL(+)). These effects were observed when modified LDL(+) reached a content of LPC and/or NEFA similar that of LDL(-). These data indicate that non-oxidized polar lipids associated with LDL promote an inflammatory response in endothelial cells and suggest that increased NEFA and LPC could be involved in the inflammatory activity of LDL(-).
Ajuts:	Ministerio de Ciencia y Tecnología SAF98/0125 Ministerio de Ciencia y Tecnología SAF2001-0480 Instituto de Salud Carlos III FISC03/01 Instituto de Salud Carlos III PI030885
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Llengua:	Anglès
Document:	Article ; recerca ; Versió sotmesa a revisió
Publicat a:	Atherosclerosis, Vol. 177 Núm. 2 (december 2004) , p. 299-305, ISSN 1879-1484

DOI: 10.1016/j.atherosclerosis.2004.07.027

19 p, 1.0 MB

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