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

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, genome stability, and cell differentiation. Furthermore, they provide novel insights into the mechanisms of diseases associated with abnormal lipid levels, such as atherosclerosis and diabetes.

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 is among early molecular changes associated with atherogenesis.

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 of the chromatin structure. It is possible that novel candidate therapeutic tools will emerge from these studies.