Immunometabolism and Cardiovascular Diseases

Our group studies mechanisms of inflammation and how these affect atherosclerosis and other vascular diseases. We have discovered that cholesterol efflux pathways in macrophages suppress inflammasome activation, which decreases neutrophil extracellular traps (NETs) in atherosclerotic plaques, 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, mainly in relation to CAR T cell therapy
• Role of inflammasome activation in pulmonary arterial hypertension

As part of our consortium PLAK TALK, we are currently studying 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.

In extending our findings on the regulation of T cell function by cholesterol accumulation, 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), and the functionality of CAR T cells (collaboration Prof. G.A. Huls and Prof. E. Bremer, Hematology).

We have recently shown that the inflammasome is activated in pulmonary arterial hypertension (PAH) and are currently investigating the therapeutic potential and regulators of NLRP3 inflammasome activation in pediatric PAH (collaboration Prof. R.M.F. Berger and Dr. J.M. Douwes, Pediatric Cardiology).