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Omega-3 Fatty Acids and the Regulation of Expression of Endothelial Pro-Atherogenic and Pro-Inflammatory Genes

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Abstract

By partially replacing the corresponding omega-6 analogues in membrane phospholipids, omega-3 fatty acids have been shown to decrease the transcriptional activation of genes — e.g., adhesion molecules, chemoattractants, inflammatory cytokines — involved in endothelial activation in response to inflammatory and pro-atherogenic stimuli. This regulation occurs, at least in part, through a decreased activation of the nuclear factor-κB system of transcription factors, secondary to decreased generation of intracellular hydrogen peroxide. Such regulation by omega-3 fatty acids is likely linked to the presence of a higher number of double bonds in the fatty acid chain in omega-3 compared with omega-6 fatty acids. By similar mechanisms, omega-3 fatty acids have been recently shown to reduce gene expression of cyclooxygenase-2, an inflammatory gene involved, through the activation of some metalloproteinases, in plaque angiogenesis and plaque rupture. The quenching of gene expression of pro-inflammatory pro-atherogenic genes by omega-3 fatty acids has consequences on the extent of leukocyte adhesion to vascular endothelium, early atherogenesis and later stages of plaque development and plaque rupture, ultimately yielding a plausible comprehensive explanation for the vasculoprotective effects of these nutrients.

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Acknowledgment

We are indebted to all our former and current collaborators at the Laboratory for Thrombosis and Vascular Research at the CNR Institute of Clinical Physiology in Pisa, the Laboratory for Atherosclerosis Research at the CNR Institute of Clinical Physiology in Lecce, and the Experimental Cardiology Laboratory at the “G. d’Annunzio” Foundation in Chieti, for the experimental data on which most of the considerations here highlighted are based.

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  1. Chair of Cardiology, “G. d’Annunzio” University, Chieti, and C.N.R. Institute of Clinical Physiology, Pisa

    R. De Caterina

  2. Chair of Cardiology, “G. d’Annunzio” University, Chieti, and C.N.R. Institute of Clinical Physiology, Pisa, Lecce, Italy

    M. Massaro

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  1. R. De Caterina
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De Caterina, R., Massaro, M. Omega-3 Fatty Acids and the Regulation of Expression of Endothelial Pro-Atherogenic and Pro-Inflammatory Genes. J Membrane Biol 206, 103–116 (2005). https://doi.org/10.1007/s00232-005-0783-2

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