Peripheral blood mononuclear cell hyperresponsiveness in patients with premature myocardial infarction without traditional risk factors

An increasing number of patients develop an atherothrombotic myocardial infarction (MI) in the absence of standard modifiable risk factors (SMuRFs). Monocytes and macrophages regulate the development of atherosclerosis, and monocytes can adopt a long-term hyperinflammatory phenotype by epigenetic reprogramming, which can contribute to atherogenesis (called trained immunity). We assessed circulating monocyte phenotype and function and specific histone marks associated with trained immunity in SMuRFless patients with MI and matched healthy controls. Even in the absence of systemic inflammation, monocytes from SMuRFless patients with MI had an increased overall cytokine production capacity, with the strongest difference for LPS-induced interleukin-10 production, which was associated with an enrichment of the permissive histone marker H3K4me3 at the promoter region. Considering the lack of intervenable risk factors in these patients, trained immunity could be a promising target for future therapy.

Automated summary

An increasing number of patients develop non-traditional risk factor-induced myocardial infarction, and this study investigated the role of trained immunity in these patients. It was found that monocytes from patients with myocardial infarction had increased cytokine production capacity, particularly interleukin-10, which was associated with specific histone marks. Considering the lack of intervenable risk factors, trained immunity could be a promising target for future therapy.