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

ABSTRACT: An increasing number of patients develop a myocardial infarction (MI) in the absence of standard modifiable risk factors (SMuRFs). Atherosclerosis is characterized by a chronic arterial wall inflammation in which monocyte-derived macrophages play a pivotal role. Trained immunity – a long lasting hyperreactive state of innate immune cells – might contribute to the development of atherosclerosis. This study investigated whether trained immunity is observed in this specific patient group. 20 SMuRFless MI patients who suffered an atherothrombotic myocardial infarction > 1 year and < 4 years before inclusion were recruited. All patients were younger than 50 years of age during the index event. Patients were matched to 18 healthy controls without coronary atherosclerosis as determined by a coronary CT-scan. Blood samples were obtained two weeks after interrupting statins in patients and starting aspirin therapy in controls to match relevant medication use. Circulating inflammatory parameters and monocytes were analyzed, with an in-depth focus on peripheral blood mononuclear cell (PBMC) function, and monocyte phenotype, RNA expression and epigenetic histone markers. PBMCs from SMuRFless patients showed higher cytokine production upon ex vivo stimulation. Although baseline RNA expression and monocyte activations markers were largely unchanged, enrichment of the transcriptionally permissive histone marker H3K4me3 on the promoter region of cytokine genes was observedIL-10 genes was observed. This existed without differences in systemic inflammation. Circulating monocytes in young SMuRFless MI patients have a hyperresponsive functional and epigenetic phenotype, indicative of trained immunity. In the absence of traditional risk factors, this could be a promising target for future therapy in these patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE229044 | GEO | 2023/07/19

REPOSITORIES: GEO