Immunometabolism and Cardiovascular diseases

We study mechanisms of inflammation and how this affects atherosclerosis and other CVD. We have discovered that cholesterol efflux pathways in macrophages suppress inflammasome activation, decreasing neutrophil extracellular traps (NETs) in atherosclerotic plaques, as such promoting plaque stability. More recently, we found that deficiency of cholesterol efflux pathways in T cells increases T cell apoptosis, which decreases macrophage inflammation and atherosclerosis.

Our main fields of research interest include:

• Crosstalk between macrophages, T cells, and vascular cells in atherosclerotic plaques
• Effects of cholesterol accumulation on T cell function
• Role of inflammasome activation in pulmonary arterial hypertension

In our consortium PLAK TALK, we study the crosstalk of macrophages and T cells with vascular cells in atherosclerotic plaques to identify mediators of plaque stability that may serve as new therapeutic targets for CVD (collaboration Dr. Jason Tarkin, Dr. Meritxell Nus, Dr Helle Jørgensen (University of Cambridge) and Prof. dr. Lars Maegdefessel (Technical University Munich)). We carry out mechanistic studies to investigate how pathways regulating intracellular cholesterol transport affect T cell activation (collaboration Prof. G. van den Bogaart, Molecular Immunology, RUG), and the functionality of CAR T cells (collaboration Prof. dr. G.A. Huls and Prof. dr. E. Bremer, UMCG Dept of Hematology).

Recently we showed that the inflammasome is activated in pulmonary arterial hypertension (PAH). Currently, we investigate regulators of NLRP3 inflammasome activation in pediatric PAH (collaboration Prof. dr. R.M.F. Berger and Dr. J.M. Douwes, Pediatric Cardiology).