Innate immune memory in cardiometabolic disease.

Low-grade systemic inflammation is a key pathophysiological component of atherosclerotic cardiovascular disease (CVD), and long-term activation of myeloid cells is thought to be crucial for these effects. Obesity and associated metabolic complications including hyperglycaemia and dyslipoproteinaemia can induce long-lasting inflammatory reprogramming of the innate immune cells and their bone marrow progenitors, which in turn contributes to atherosclerosis. In this review, we discuss the mechanisms through which innate immune cells undergo long-term changes in their functional, epigenetic, and metabolic characteristics upon even short-term exposure to endogenous ligands, a process also termed 'trained immunity'. Inappropriate induction of trained immunity leads to the development of long-lasting hyperinflammatory and proatherogenic changes in monocytes and macrophages, an important factor in the development of atherosclerosis and CVDs. Knowledge of the specific immune cells and the distinct intracellular molecular pathways involved in the induction of trained immunity will reveal novel pharmacological targets that could be used to prevent or treat CVDs in the future.

Bahrar H ，Bekkering S ，Stienstra R ，Netea MG ，Riksen NP ... -  《-》

Trained Immunity in Atherosclerotic Cardiovascular Disease.

Flores-Gomez D ，Bekkering S ，Netea MG ，Riksen NP ... -  《-》

Innate Immune Memory in Monocytes and Macrophages: The Potential Therapeutic Strategies for Atherosclerosis.

Guo Z ，Wang L ，Liu H ，Xie Y ... -  《Cells》

Trained immunity and atherosclerotic cardiovascular disease.

Riksen NP 《-》

The epigenetic memory of monocytes and macrophages as a novel drug target in atherosclerosis.

Atherosclerosis is characterized by a persistent inflammation of the arterial wall. Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. After stimulation, monocytes can adopt a long-term proinflammatory phenotype. This nonspecific memory of innate immune cells is mediated by epigenetic reprogramming and has recently been termed "trained innate immunity." The goal of this study was to describe the potential role of trained immunity in the development of atherosclerosis and to discuss the potential clinical implications of this concept. We performed a comprehensive literature search (PubMed) on the role of epigenetic programming of histones, and of trained immunity in particular, in atherogenesis. In vitro studies demonstrate that modified LDL particles can induce a long-term proinflammatory phenotype in monocytes/macrophages by epigenetic reprogramming at the level of histone methylation. This scenario is associated with increased production of proatherogenic cytokines and chemokines and increased formation of foam cells. Preclinical evidence suggests that trained innate immunity may contribute to vascular wall inflammation in patients with risk factors for atherosclerosis. Epigenetic reprogramming is regulated by enzymes that are amenable to pharmacologic modulation. Therefore, this mechanism could be used to develop novel pharmacologic targets for the prevention or treatment of atherosclerotic vascular disease.

Bekkering S ，Joosten LA ，van der Meer JW ，Netea MG ，Riksen NP ... -  《-》