Inhibition of TNFα-induced adhesion molecule expression by (Z)-(S)-9-octadecenamide, N-(2-hydroxyethyl,1-methyl).

ABSTRACT

Inflammation is a primary event in atherogenesis. Oleoylethanolamide (OEA), a naturally occurring fatty-acid ethanolamide, lowers lipid levels in liver and blood through activation of the nuclear receptor, peroxisome proliferator-activated receptor-alpha (PPARα). We designed and synthesized (Z)-(S)-9-octadecenamide, N-(2-hydroxyethyl, 1-methyl) (OPA), an OEA analog. The present study investigated the effect of OPA on the expression of adhesion molecules in human umbilical vein endothelial cells (HUVEC). OPA inhibited expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) stimulated by Tumor Necrosis Factor-α (TNF-α) via activation of PPARα. This inhibition of VCAM-1 and ICAM-1 expression decreased adhesion of monocyte-like cells to stimulated endothelial cells. These results demonstrate that OPA may have anti-inflammatory properties. Our results thus provide new insights into possible future therapeutic approaches to the treatment of atherosclerosis.