Hepatovascular control of disease susceptibility and resistance via circulating blood factors
Liver sinusoidal endothelial cells (LSEC) control blood plasma composition by endocytosis of circulating ligands involving scavenger receptors Stabilin-1 (Stab1) and Stabilin-2 (Stab2). We have shown that clearance of the peripheral blood by LSEC determines disease susceptibility and resistance. Deficiency of either Stab1 or Stab2 as well as anti-Stabilin monoclonal antibodies provide protection from atherosclerosis. This involves novel ligands of Stab1 and Stab2 such as TFGBi, Postn and Reln as well as transcriptomic alterations in monocytes including downregulation of pro-atherogenic transcription factor Egr1. Our grup strives to elucidate the underlying molecular events including downstream processes of vesicular transport and cytoskeletal dynamics and to assess the role of Stab1/Stab2 in immune complex diseases. Overall, our research on hepatovascular clearance will help to identify opportunities for targeted adjustments of the plasma proteome for preventive and therapeutic applications.