Long-term monocyte activation after coronary artery bypass grafting: An exploratory prospective observational study.

Major surgery such as coronary artery bypass grafting (CABG) is associated with an increased post-operative risk of atherosclerotic cardiovascular events. Cells of the innate immune system can adopt a long-lasting pro-inflammatory and atherogenic phenotype after brief exposure to exogenous or endogenous inflammatory stimuli, a process called "trained immunity". We hypothesized that the surgery-induced inflammation leads to sustained alterations in monocyte function, which promote the subsequent occurrence of cardiovascular events. Blood from 13 patients undergoing elective CABG was obtained before, 3-7 days (median 4) after, and 6-8 weeks (median 6) weeks after surgery. At 3-7 days postoperatively, circulating C-reactive protein (CRP) concentration, leukocyte counts and ex vivo Peripheral Blood Mononuclear Cell (PBMC) IL-6, TNFα and IL-1Ra production after stimulation (with various inflammatory stimuli) were significantly increased. Simultaneously, there was a reduction in monocyte HLA-DR expression. 6-8 weeks after CABG there was an ongoing systemic pro-inflammatory state with higher CRP concentrations, increased stimulated ex vivo PBMC IL-6 production, changes in monocytes subsets, and a higher expression of CCR2 on monocytes compared to baseline. In conclusion, CABG induces a persistent systemic inflammatory reaction with a sustained activated monocyte phenotype. This might contribute to the increased atherosclerotic cardiovascular event risk observed in cardiac surgery patients.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wilson F. Abdo reports financial support was provided by Netherlands Organisation for Health Research and Development. Mihai Netea reports financial support was provided by European Research Council. Mihai Netea reports financial support was provided by Dutch Research Council. Niels Riksen reports financial support was provided by Netherlands Heart Foundation. Siroon Bekkering reports financial support was provided by Netherlands Heart Foundation. Mihai Netea reports a relationship with TTxD that includes: equity or stocks. Mihai netea reports a relationship with Lemba that includes: equity or stocks. Mihai Netea reports a relationship with Biotrip that includes: equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. MGN is scientific founder of TTxD, Lemba and Biotrip.
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