Trained immunity in diabetes and hyperlipidemia: Emerging opportunities to target cardiovascular complications and design new therapies

Some metabolic diseases, such as diabetes and hyperlipidemia, are associated with a state of inflammation, which adversely affects cardiovascular health. Emerging evidence suggests that long-term hyperactivation of innate immune cells and their bone marrow progenitors, termed trained immunity, functions to accelerate atherosclerosis and its complications in cardiometabolic diseases. This review will focus on how trained immunity is established, particularly through metabolic and epigenetic reprogramming, to cause persistent and deleterious changes in immune cell function, even after the original stimulus has been corrected or removed. Understanding the mechanisms driving maladaptive trained immunity and its fundamental contribution to cardiovascular disease might enable the development of novel disease-modifying therapeutics for the reduction in cardiovascular risk in diabetes, hyperlipidemia, and related cardiometabolic states.