Modeling OxLDL Epigenetic Innate Immune Training of Monocytes in Early Atherosclerotic Plaques

Abstract


 Atherosclerotic cardiovascular disease (atherosclerosis) is the leading cause of death worldwide. While atherogenesis is generally well understood, the sustained inflammation seen in some rapidly developing plaques remains largely unexplained. Recent research in epigenetics reports chromatin remodeling with significant pro-atherogenic effects in human monocytes exposed to oxLDL. Data collected from isolated monocytes in vitro suggests that epigenetic innate immune training may explain the observed persistent inflammatory state, however, research has yet to quantify the effects of training on early plaque dynamics. In the present study, I employ a partial differential equation and agent based mathematical model to describe key markers of atherogenesis in a system with “untrained” or “trained” monocytes. Time dependent solutions of the model suggest that innate immune training with oxLDL produces a pronounced pro-inflammatory response which has significant effects on the counts of plaque macrophages and foam cells. These results provide further support for the targeting of the epigenome in the treatment of atherosclerosis.