Vascular Control of Organ Function
B3: Hepatovascular control of disease susceptibility and resistance via circulating blood factors
Liver sinusoidal endothelial cells are unique organ-specific endothelial cells that constitute the largest sinusoidal vascular bed of the body. Liver sinusoidal endothelial cells are considered the most active endocytes of mammals and maintain blood and tissue homeostasis. The genetic ablation of liver sinusoidal endothelial cells-characteristic scavenger receptors Stab1 and Stab2 causes severe renal glomerulosclerosis and albuminuria by altering the molecular composition of the blood plasma. Preliminary data indicate that Stabilin-dependent circulating molecules can have either protective or harmful functions in different physiologic and pathophysiologic settings. The opposite roles of Stab1- and Stab2-mediated clearance during metabolic and fibrotic diseases will be the focus of this project. Elucidation of the underlying mechanisms that provide protection and confer susceptibility to atherosclerosis and organ fibrosis, respectively, will advance our understanding of systemic angiocrine effects and we envision to establish proof-of-concept for Stabilin-targeted therapies.