'Angiodiversity' refers to the structural and functional heterogeneity of endothelial cells (EC) along the segments of the vascular tree and especially within the microvascular beds of different organs . Organotypically differentiated EC ranging from continuous, barrier-forming endothelium to discontinuous, fenestrated endothelium perform organ-specific functions such as the maintenance of the tightly sealed blood-brain barrier or the clearance of macromolecular waste products from the peripheral blood by liver EC-expressed scavenger receptors . The microvascular bed of the liver, composed of discontinuous, fenestrated liver sinusoidal endothelial cells (LSEC), is a prime example of organ-specific angiodiversity . Anatomy and development of LSEC have been extensively studied by electron microscopy as well as linage-tracing experiments . Recent advances in cell isolation and bulk transcriptomics or single-cell RNA sequencing techniques allowed the identification of distinct LSEC molecular programs and have led to the identification of LSEC subpopulations . LSEC execute homeostatic functions such as fine tuning the vascular tone, clearing noxious substances from the circulation, and modulating immunoregulatory mechanisms . In recent years, the identification and functional analysis of LSEC-derived angiocrine signals, which control liver homeostasis and disease pathogenesis in an instructive manner, marks a major change of paradigm in the understanding of liver function in health and disease . This review summarizes recent advances in the understanding of liver vascular angiodiversity and the functional consequences resulting thereof.
Index: Angiocrine signaling, Angiodiversity, Endothelial cell heterogeneity, Liver vasculature, Sinusoids