In vivo and in vitro inhibition of monocyte adhesion to endothelial cells and endothelial adhesion molecules by eicosapentaenoic acid

Hideto Yamada, Masayuki Yoshida, Yasutaka Nakano, Takayoshi Suganami, Noriko Satoh, Tomoya Mita, Kosuke Azuma, Michiko Itoh, Yukio Yamamoto, Yasutomi Kamei, Minoru Horie, Hirotaka Watada, Yoshihiro Ogawa

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Abstract

Objective - A large-scale, prospective, randomized clinical trial has recently revealed that the addition of highly purified eicosapentaenoic acid (EPA) to low-dose statin therapy significantly reduces the incidence of major coronary events. Here we investigated in vivo and in vitro effect of EPA on monocyte adhesion to endothelial cells and adhesion molecules. Methods and Results - A new en face immunohistochemistry of endothelial surface in combination with confocal microscopy revealed marked reduction of lipopolysaccharide (LPS)-induced monocyte adhesion to the aortic endothelium in parallel with the suppression of vascular cell adhesion molecule 1 (VCAM-1) and nuclear translocation of nuclear factor-κB p65 in EPA-treated mice relative to vehicle-treated groups. In an in vitro adhesion assay system under physiological flow conditions, EPA inhibited LPS-induced monocyte adhesion and endothelial adhesion molecules. We found significant decrease in plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1) and sVCAM-1 in patients with the metabolic syndrome after a 3-month administration of highly purified EPA (1.8 g daily). Multivariate regression analysis revealed that EPA administration is the only independent determinant of sICAM-1 and sVCAM-1. Conclusions - This study provides evidence that EPA inhibits monocyte adhesion to endothelial cells in parallel with the suppression of endothelial adhesion molecules in vivo and in vitro.

Original languageEnglish
Pages (from-to)2173-2179
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume28
Issue number12
DOIs
Publication statusPublished - Dec 1 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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    Yamada, H., Yoshida, M., Nakano, Y., Suganami, T., Satoh, N., Mita, T., Azuma, K., Itoh, M., Yamamoto, Y., Kamei, Y., Horie, M., Watada, H., & Ogawa, Y. (2008). In vivo and in vitro inhibition of monocyte adhesion to endothelial cells and endothelial adhesion molecules by eicosapentaenoic acid. Arteriosclerosis, thrombosis, and vascular biology, 28(12), 2173-2179. https://doi.org/10.1161/ATVBAHA.108.171736