New scientific article in Cell metabolism 2019.
Patients with hypercholesterolemia have an increased risk for atherosclerotic cardiovascular disease, and despite lipid lowering with statins, an important residual risk remains. We hypothesize that this is due to persistent pro-inflammatory reprogramming of circulating monocytes. Monocyte derived macrophages are key components of atherosclerotic plaques. These cells can build a long-term pro-inflammatory phenotype after brief exposure to atherogenic compounds. This immune memory is mediated by metabolic and epigenetic reprogramming and is termed trained immunity. Bekkering et al. show that monocytes from patients with familial hypercholesterolemia have a trained immunity phenotype and that lipid lowering with statins does not revert this pro-inflammatory phenotype. This study is performed in a close collaboration between Radboud University Medical Center, University of Medicine and Pharmacy, Cluj-Napoca and Academic Medical Center, all partners in the REPROGRAM consortium.