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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2281.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Electronegative LDL From Normolipemic Subjects Induces IL-8 and Monocyte Chemotactic Protein Secretion by Human Endothelial Cells

Conxita De Castellarnau; José Luis Sánchez-Quesada; Sonia Benítez; Roser Rosa; Luis Caveda; Luis Vila; Jordi Ordóñez-Llanos

From the Institut de Recerca (C.d.C., R.R., L.C., L.V.) and Servei de Bioquímica (J.L.S-Q, S.B., J.O-Ll.), Hospital de la Santa Creu i Sant Pau, Departament de Bioquímica i Biología Molecular (S.B., J.O.-Ll.), Universitat Autònoma, Barcelona, Spain.

Correspondence to Conxita de Castellarnau, Rosellon 12, 4°1^a Esc A, 08029 Barcelona, Spain. E-mail ccastellarnauc{at}medynet.com

Abstract—The presence in plasma of an electronegative LDL subfraction [LDL(-)] cytotoxic for endothelial cells (ECs) has been reported. We studied the effect of LDL(-) on the release by ECs of molecules implicated in leukocyte recruitment [interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1)] and in the plasminogen activator inhibitor-1 (PAI-1). LDL(-), isolated by anion-exchange chromatography, differed from nonelectronegative LDL [LDL(+)] in its higher triglyceride, nonesterified fatty acid, apoprotein E and apoprotein C-III, and sialic acid contents. No evidence of extensive oxidation was found in LDL(-); its antioxidant and thiobarbituric acid–reactive substances contents were similar to those of LDL(+). However, conjugated dienes were increased in LDL(-), which suggests that mild oxidation might affect these particles. LDL(-) increased, in a concentration-dependent manner, the release of IL-8 and MCP-1 by ECs and was a stronger inductor of both chemokines than oxidized LDL (oxLDL) or LDL(+). PAI-1 release increased slightly in ECs incubated with both LDL(-) and oxLDL but not with LDL(+). However, no cytotoxic effects of LDL(-) were observed on ECs. Actinomycin D inhibited the release of IL-8 and MCP-1 induced by LDL(-) and oxLDL by up to 80%, indicating that their production is mediated by protein synthesis. Incubation of ECs with N-acetyl cysteine inhibited production of IL-8 and MCP-1 induced by LDL(-) and oxLDL by >50%. The free radical scavenger butylated hydroxytoluene slightly inhibited the effect of oxLDL but did not modify the effect of LDL(-). An antagonist (BN-50730) of the platelet-activating factor receptor inhibited production of both chemokines by LDL(-) and oxLDL in a concentration-dependent manner. Our results indicate that LDL(-) shows proinflammatory activity on ECs and may contribute to early atherosclerotic events.

Key Words: LDL • electronegative LDL • interleukin-8 • monocyte chemotactic protein • endothelial cells

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