Peripheral blood mononuclear cell hyperresponsiveness in patients with premature myocardial infarction without traditional risk factors
Jan-Quinten Mol,
Julia van Tuijl,
Siroon Bekkering,
Charlotte D.C.C. van der Heijden,
Sander A.J. Damen,
Benjamin C. Cossins,
Liesbeth van Emst,
Tim M. Nielen,
Laura Rodwell,
Yang Li,
Gheorghe A.M. Pop,
Mihai G. Netea,
Niels van Royen,
Niels P. Riksen,
Saloua El Messaoudi
Affiliations
Jan-Quinten Mol
Department of Cardiology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
Julia van Tuijl
Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
Siroon Bekkering
Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
Charlotte D.C.C. van der Heijden
Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
Sander A.J. Damen
Department of Cardiology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
Benjamin C. Cossins
Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
Liesbeth van Emst
Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
Tim M. Nielen
Department of Cardiology, Canisius Wilhelmina Hospital, 6532 SZ Nijmegen, the Netherlands
Laura Rodwell
Section Biostatistics, Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
Yang Li
Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; Department of Computational Biology for Individualised Medicine, Centre for Individualised Infection Medicine (CiiM) & TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), 30625 Hannover, Germany
Gheorghe A.M. Pop
Department of Cardiology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
Mihai G. Netea
Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany
Niels van Royen
Department of Cardiology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
Niels P. Riksen
Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
Saloua El Messaoudi
Department of Cardiology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; Corresponding author
Summary: 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.
