Innate immune memory in cardiometabolic disease

Author:

Bahrar Harsh1,Bekkering Siroon1ORCID,Stienstra Rinke12,Netea Mihai G13,Riksen Niels P1ORCID

Affiliation:

1. Radboud University Medical Center, Department of Internal Medicine and Radboud Institute for Molecular Life Sciences , 463, Geert Grooteplein Zuid 8, 6525 GA Nijmegen , The Netherlands

2. Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University , Wageningen , The Netherlands

3. Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn , Bonn , Germany

Abstract

AbstractLow-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.

Funder

IN-CONTROL CVON

Dutch Heart Foundation in the Hague

European Research Council

Dutch Research Council

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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