New article found in European Heart Journal from Oct /17  from rndtl from IV

https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehx581/4563761

New knowledge about inflammatory signalling, particularly in the areas of endogenous homeostatic pathways and inflammation resolution also provides the promise for new therapeutic options that can adequately meet the therapeutic challenges in CID and atherosclerosis. The abundant presence of epigenetic alterations in both CID and atherosclerosis underlines the potential for clinical applications. In line with this, the potential of epigenetic alterations as molecular biomarkers are being explored for CVD risk evaluation, early detection, prognosis stratification, and treatment response prediction. On the other hand, unlike genetic mutations, epigenetic changes, including DNA methylation and histone modifications, are pharmacologically reversible, making them attractive targets in therapeutic strategies.

Novel insights that will develop by a systems biology approach of trained monocytes is highly likely to identify novel therapeutic targets to prevent or treat atherosclerosis.80 Several preclinical studies have already provided proof-of-concept data that drugs that modulate the activity of epigenetic writers or erasers, such as HDAC inhibitors, can modulate the development of atherosclerosis.120,121Furthermore, BET-inhibitors such as RVX-208, JQ1, and I-Bet that inhibit the interaction of BET proteins with acetylated histone tails, showed a repression of pathways that contribute to CVD and inhibition of atherogenesis in mouse models.122–124 Drugs leading to the reverse reprogramming of macrophages are for example cyclodextrin. Via the LXR pathway, cyclodextrin supports atherosclerosis regression by transcriptional reprogramming leading to increased cholesterol efflux and anti-inflammatory effects,7thereby reversing the initial pro-inflammatory response upon cholesterol crystal accumulation. Major advances have been made in the field of oncology with aberrant DNA methylation profiles and alterations in histone modification being linked to specific cancers and tumour progression, some of which are already used in the clinic.125 The discrepancy between major advances in the oncology field and scarcity of data in the cardiovascular and rheumatology field illustrates that an organized effort to address the potential of epigenetic modulation in atherosclerosis and CID is long overdue.

In conclusion, epigenetic reprogramming has been shown to play a role in perpetuation of the chronic inflammatory state in atherosclerosis by promoting activation of innate immune cells. Since innate immune cell activation serves as a mostly inappropriate amplification loop which is not critically involved in primary defence against infectious diseases, this novel pathway may offer a safe and novel method to lower this redundant inflammatory activity in absence of the danger of eliciting immune suppression. Therefore, further research is warranted to better understand cellular and molecular mechanisms mediating trained immunity, offering the opportunity of opening this area for future therapeutic agents in the cardiovascular area.