Harnessing the power of endothelial metabolism could be a novel approach to reduce the atherogenic milieu in the bone marrow niche and atherosclerotic plaque. For this project, AGEM Principal Investigator Jeffrey Kroon received a prestigious ERC Starting Grant.

Inflammation is an important driver of atherosclerosis, the primary cause of global morbidity and mortality in emerging and developed countries. New strategies to reduce atherosclerotic cardiovascular disease (CVD) risk are therefore eagerly needed. Kroon’s research group recently found that atherogenic inflammatory stimuli rewire cellular metabolism in endothelial cells (ECs) and thereby contribute to atherosclerosis progression. Defining the intricate link between EC inflammation, metabolic rewiring and functional consequences for the vasculature will open new avenues for therapeutic strategies in CVD. Recent work of Kroon’s group shows that CVD-associated metabolic changes in ECs can affect their secretome. In turn, the endothelial secretome disrupts both stem cell function in the bone marrow niche and macrophage activation in the plaque microenvironment, two highly vascularized tissue compartments that drive atherosclerosis progression. With this ERC Starting Grant, the group will unravel how EC metabolism is affected in atherosclerosis, what the impact of this altered EC metabolism is for stem cell function in the bone marrow niche and for macrophage activation in the plaque. Their ultimate goal is to define how interventions in EC metabolism improve tissue function and halt CVD development.