Chromatin modification by lipids and lipoprotein components: an initiating event in atherogenesis?

Purpose of review This review examines recent evidence proposing that lipids and lipoproteins can, act as nuclear, factors regulating chromatin structure. These novel data broaden our understanding of the mechanisms by which lipoproteins can affect basic biological phenomena such as transcription, genomestablility and cell differentiation. Furthermore, they provide novel insights into the mechanisms of diseases associated with abnormal lipid levels, such as atherosclerosis and diabetes. Recent findings Data consistent, with a role, for lipids and lipoprotein components as nuclear factors, as well as initiators of cytoplasmic signalling events resulting in chromatin modification, have been published in the past year. In particular, new insights into the mechanisms of interaction between chromatin and small lipid molecules such as short-chain fatty acids and cholesterol, and endogenous lipid peroxidation products have been obtained. Furthermore, it has been shown that hyperlipidaemic lipoprotein profiles are associated with aberrant DNA methylation, patterns at early stages of atherosclerosis in mice and in cultured human macrophages, suggesting that a rearrangement of DNA methylation patterns-it among early molecular changes associated with atherogenesis. Summary The findings described here are prompting efforts to understand further how lipids and lipoprotein components can affect gene expression in, normal and pathological cell behaviour through regulation in the chromatin structure. It is possible that novel candidate therapeutic tools will emerge from these studies.