Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Review J Nutrigenet Nutrigenomics 2008;1:4–23 DOI: 10.1159/000109871 Omega–3 Fatty Acids, Inflammation and Angiogenesis: Nutrigenomic Effects as an Explanation for Anti-Atherogenic and Anti-Inflammatory Effects of Fish and Fish Oils Marika Massaro a, b Egeria Scoditti a, b Maria Annunziata Carluccio a, b Maria Rosa Montinari b Raffaele De Caterina a, c a CNR Institutes of Clinical Physiology, Pisa and Lecce, b University of Lecce, Ecotekne, Lecce, and c Chair of Cardiology, ‘G. d’Annunzio’ University, Chieti, Italy This series of investigations configures a clear example of nutrigenomics, i.e. how nutrients may affect gene expres- sion, ultimately affecting a wide spectrum of human dis- eases. Copyright © 2007 S. Karger AG, Basel Omega–3 fatty acids have recently emerged as an ex- ample of nutrients able to modulate the expression of genes involved in inflammation and atherosclerosis. Their ability to influence such processes is therefore a good example of nutrigenomics. This review summarizes the evidence to this regard. Since a description of the mo- lecular events underlying endothelial changes in athero- sclerosis is important for an understanding of the mode of action of these nutrients, a short review of current con- cepts of inflammation and atherosclerosis gives the back- ground to place their genomic effect in context. Inflammation in Atherosclerosis Atherosclerosis is currently regarded as a dynamic process arising from functional inflammatory changes in the endothelium of conduit arteries [1] . Here the vascular endothelium, no longer regarded as the passive lining of Key Words Omega–3 fatty acids  n–3 fatty acids  Adhesion molecules  Endothelium  Endothelial activation  Atherosclerosis  Cyclooxygenase-2  Plaque angiogenesis  Plaque rupture Abstract Atherosclerosis is a dynamic process with inflammatory as- pects playing a considerable pathogenetic role. In this pro- cess, the vascular endothelium is the key regulator of vas- cular function, promoting the maintenance of vascular homeostasis or the progression towards vascular disease. In the past 30 years, the dietary intake of omega–3 (n–3) poly- unsaturated fatty acids – mainly derived from fish – has emerged as an important way to modify cardiovascular risk through beneficial effects on all stages of atherosclerosis. This review specifically focuses on the modulating effects of n–3 fatty acids on molecular events involved in early and late atherogenesis, including effects on endothelial expression of adhesion molecules, as well as pro-inflammatory and pro- angiogenic enzymes. By accumulating in endothelial mem- brane phospholipids, omega–3 fatty acids have been shown to decrease the transcriptional activation of several genes through a decreased activation of the nuclear factor- B sys- tem of transcription factors. This occurs secondary to de- creased generation of intracellular reactive oxygen species. Published online: October 17, 2007 Raffaele De Caterina, MD, PhD Institute of Cardiology and Center of Excellence on Aging ‘G. d’Annunzio’ University – Chieti, C/o Ospedale S. Camillo de Lellis Via Forlanini, 50, IT–66100 Chieti (Italy) Tel. +39 0871 41512, Fax +39 0871 402 817, E-Mail rdecater@unich.it © 2007 S. Karger AG, Basel 1661–6499/08/0012–0004$24.50/0 Accessible online at: www.karger.com/jnn