Valérie Marcil¹, Edgard Delvin², Devendra Amre³, Daniel Sinnett³, Geneviève Mailhot¹, Ernest Seidman^4,5 and Emile Levy1,4

Departments of ¹Nutrition, ²Biochemistry and ³Pediatrics, CHU Ste-Justine, Université de Montréal, 3175 Côte Sainte Catherine, Montreal, Quebec, H3T 1C5, Canada. ⁴Group on the Intestinal Epithelium, Canadian Institute of Health Research and Department of Cellular Biology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada. ⁵Research Institute, McGill University, Campus MGH, C10.148.6, Montreal, Quebec, Canada.

Abstract

Circumstantial evidence suggests that oxidative stress plays a crucial role in the initiation and progression of atherosclerosis, but little is known about the relationship between oxidative stress per se, cholesterol transport and endothelial cell integrity. The aim of the present work is to tackle this issue by treating human umbilical vein endothelial cells (HUVEC) with iron/ascorbate for 4 and 8 hours and by subsequently evaluating the cholesterol flux, the gene expression status of cholesterol transporters, nuclear receptors and adhesion molecules, as well as the cellular adhesion of THP-1 monocytes to HUVEC. The incubation of HUVEC with iron/ascorbate resulted in marked lipid peroxidation as reflected by high malondialdehyde levels, which were reduced by pre-treatment with the antioxidant Trolox. Our experiments could not reveal any modifi cations in the protein and gene expression of the transporters (ABCA1, SR-BI, LOX-1), the adhesion molecules (VCAM-1, ICAM-1 and E-selectin) and the nuclear receptors (PPARs and LXRs) under the influence of iron/ascorbate. However, oxidative stress enhanced monocyte adhesion to HUVEC, induced the gene expression of ICAM-1, E-selectin and MCP-1, whereas it downregulated eNOS mRNA in the presence of monocytes. Overall, our data suggest that oxidative stress is more harmful in the presence of heterocellular communication between endothelial cells and monocytes.

Discussion
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