Conclusions and future trends

Dietary consumption of polyphenols is associated with a lower risk of degenerative diseases. In particular, protection of serum lipids from oxidation, which is a major step in the development of arteriosclerosis, has been demonstrated. More recently, new avenues have been explored in the capacity of polyphenols to interact with the expression of the human genetic potential. The understanding of the interaction between this heterogeneous class of compounds and cellular responses, due either to their ability to interplay in the cellular antioxidant network or directly to affect gene expression has increased.

One main line of future research could be in the inhibitory/activating effect on key enzymes involved in the pathogenesis of arteriosclerosis. In particular, enzymes regulating signal transduction involved in phosphory-lation of proteins, such as PKC and tyrosine protein kinase, seems to be somehow modulated by different polyphenols and may represent a possible target for polyphenol activity.

The ability of polyphenols to modulate redox-sensitive pathways of cellular response in endothelial cells, lymphocytes and smooth muscle cells has also been observed.Although some data is already available on NF-kB,AP-1 and other transcription factors sensitive to the cellular redox status in response to oxidatively modified LDL, the cellular response to lipoproteins modified by the exposure to reactive nitrogen species, is still largely unknown. The unravelling of the mechanisms of the regulation of tran-

scriptional control of gene expression will possibly be a promising future line of investigation.

In conclusion, polyphenols seem to be able to affect the expression of genes involved in the pathogenesis of atherogenesis. Cytokines and adhesion molecules appear to be among the most important genes expressed during the pro-inflammatory situation which precedes the formation of the atheroma, and have also been reported to be affected, at least in part, by phenolics. We can therefore foresee that a considerable effort will be addressed to the study of the mechanisms through which polyphenols affect the control of the espression of these genes. These studies will give a solid background for the understanding of the molecular mechanisms of the beneficial effects of polyphenols on human health.

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