Epigenetics in atherosclerosis and inflammation

Abstract

Introduction Epigenetics explained Epigenetic alterations are reversible Atherosclerosis Epigenetics and association with atherosclerosis Epigenetic regulation of cell activity T cells Monocytes Endothelial cells Smooth muscle cells Chemokines, their receptors and other genes involved in inflammation eNOS iNOS CCL11 (eotaxin) CCR5 Epigenetics in (vascular) inflammation KDM6B Oestrogen receptor COX2 Transcriptional regulation of MHC molecules - the role of CIITA Non-histone targets MicroRNAs Conclusions Atherosclerosis is a multifactorial disease with a severe burden on western society. Recent insights into the pathogenesis of atherosclerosis underscore the importance of chronic inflammation in both the initiation and progression of vascular remodelling. Expression of immunoregulatory molecules by vascular wall components within the atherosclerotic lesions is accordingly thought to contribute to the ongoing inflammatory process. Besides gene regulatory proteins (transcription factors), epigenetic mechanisms also play an essential and fundamental role in the transcriptional control of gene expression. These epigenetic mechanisms change the accessibility of chromatin by DNA methylation and histone modifications. Epigenetic modulators are thus critically involved in the regulation of vascular, immune and tissue-specific gene expression within the atherosclerotic lesion. Importantly, epigenetic processes are reversible and may provide an excellent therapeutic target. The concept of epigenetic regulation is gradually being recognized as an important factor in the pathogenesis of atherosclerosis. Recent research provides an essential link between inflammation and reprogramming of the epigenome. In this review we therefore discuss the basis of epigenetic regulation - and the contribution thereof in the regulation of inflammatory processes in general and during atherosclerosis in particular. Moreover we highlight potential therapeutic interventions based on epigenetic mechanisms.Stemcel biology/Regenerative medicine (incl. bloodtransfusion