Cell‑specific histone modifications in atherosclerosis (Review)

Abstract

Histone modifications are the key epigenetic mechanisms that have been identified to regulate gene expression in many human diseases. However, in the early developmental stages, such as in utero and the postnatal stages, histone modifications are essential for gene regulation and cell growth. Atherosclerosis represents a classical example of the involvement of different cell types, and their cumulative effects in the development of atheroma and the progression of the disease. Post translational modifications on proteins either induces their functional activity or renders them inactive. Post translational modifications such as methylation or acetylation on histones have been well characterized, and their role in enhancing or inhibiting specific gene expression was clearly elucidated. In the present review article, the critical roles of different histone modifications that occur in atherosclerosis have been summarized. Different histone proteins have been identified to serve a critical role in the development of atherosclerosis. Specifically, histone methylation and histone acetylation in monocytes, macrophages, vascular smooth muscle cells and in endothelial cells during the progression of atherosclerosis, have been well reported. In recent years, different target molecules and genes that regulate histone modifications have been examined for their effects in the treatment of atherosclerosis in animal models and in clinical trials. An increasing body of evidence suggests that these epigenetic changes resulting from DNA methylation and non‑coding RNA may also be associated with histone modifications, thereby indicating that novel therapeutic strategies can be developed by targeting these post translational modifications, which may in turn aid in the treatment of atherosclerosis.

Figure 1.

Histone methylation occurring during atherosclerosis. Methylation of different histone proteins and their effects on gene expression in various cell types during atherosclerosis is presented. Red arrows indicate upregulation and blue arrows indicate downregulation.

Figure 2.

Histone acetylation occurring during atherosclerosis. Acetylation of different histone proteins and their effects on regulating gene expression in monocytes and macrophages during atherosclerosis is presented. Red arrows indicate upregulation and blue arrows indicate downregulation. HDAC, histone deacetylases; IL-6, interleukin 6; MCP-1, chemokine monocyte chemoattractant protein-1; MMP12, matrix metalloproteinase 12; ABCA1, adenosine triphosphate binding cassette subfamily A member 1; ABCG1, adenosine triphosphate binding cassette subfamily G member 1; PPAR-γ, peroxisome proliferator-activated receptor-γ.