Role of Kupffer cells in hypercholesterolemia-driven cardiovascular risk – ROKHY

Cardiovascular disease (CVD) and its clinical manifestations, such as myocardial infarction and stroke, are the leading cause of mortality worldwide. Elevated plasma cholesterol concentrations are directly implicated in the development of atherosclerosis, the underlying pathology of CVD. Our previous studies have highlighted a strong relationship between macrophage (Mac) abundance and cholesterolemia. While the specific Mac population involved (and underlying mechanisms) has not been identified, hepatic Mac (Kupffer cells, KCs) were the prevailing candidate population and our new preliminary findings strongly argue for their role in the control of cholesterolemia. We now propose to explore this immunometabolic connection linking cholesterol homeostasis and KCs, and its impact on atherosclerosis development using new mouse models targeting KCs specifically. The identification of these pathways may extend our basic knowledge and may suggest new therapeutic strategies or targets in CVD.