Lymphatic Programing and Specialization in Hybrid Vessels

Abstract

Building on a large body of existing blood vascular research, advances in lymphatic research have helped kindle broader investigations into vascular diversity and endothelial plasticity. While the endothelium of blood and lymphatic vessels can be distinguished by a variety of molecular markers, the endothelia of uniquely diverse vascular beds can possess distinctly heterogeneous or hybrid expression patterns. These expression patterns can then provide further insight on the development of these vessels and how they perform their specialized function. In this review we examine five highly specialized hybrid vessel beds that adopt partial lymphatic programing for their specialized vascular functions: the high endothelial venules of secondary lymphoid organs, the liver sinusoid, the Schlemm's canal of the eye, the renal ascending vasa recta, and the remodeled placental spiral artery. We summarize the morphology and endothelial expression pattern of these vessels, compare them to each other, and interrogate their specialized functions within the broader blood and lymphatic vascular systems.

The pre-metastatic niche in lymph nodes: formation and characteristics

“…They are surrounded by pericytes embedded in a thick basement membrane [64]. HEV endothelial cells have a cuboidal shape and express general endothelial markers (CD31, CD34, VEcadherin and VEGFR-2), specific blood endothelial markers (von Willebrand factor and peripheral lymph node addressin (PNAd) and VEGFR1) [65].…”

Ras Pathways on Prox1 and Lymphangiogenesis: Insights for Therapeutics

“…Recent discoveries have identified Prox1's involvement in placental spiral artery remodeling; Prox1 begins to be expressed at E11.5 in the spiral artery endothelium of mice to promote lymphatic mimicry ( 50 ). Spiral arteries are used to supply maternal blood over to the fetal side of the placenta and thereby the fetal vasculature, with poor spiral artery remodeling being associated with pregnancy complications such as preeclampsia ( 51 , 52 ). This dual expression of LEC and BEC markers can be seen across hybrid vessels, with Prox1 as a driver for these other LEC markers.…”

Lymphangiogenesis requires Ang2/Tie/PI3K signaling for VEGFR3 cell-surface expression

“…Research in recent years has greatly increased knowledge about lymphatic vessels and vessels with hybrid lymphatic and blood vascular markers, which are now considered to play active roles in several physiological and pathological conditions. The primary function of the lymphatic vascular system is to control tissue fluid homeostasis, trafficking of immune cells, and absorption of dietary fat ( 1 – 3 ). Lymphangiogenesis and abnormal lymphatic vessel function have been associated with conditions such as obesity, atherosclerosis, and neurological disorders ( 2 , 4 ).…”