Membrane‐mediated regulation of vascular identity

Abstract

Vascular diseases span diverse pathology, but frequently arise from aberrant signaling attributed to specific membrane-associated molecules, particularly the Eph-ephrin family. Originally recognized as markers of embryonic vessel identity, Eph receptors and their membrane-associated ligands, ephrins, are now known to have a range of vital functions in vascular physiology. Interactions of Ephs with ephrins at cell-to-cell interfaces promote a variety of cellular responses such as repulsion, adhesion, attraction, and migration, and frequently occur during organ development, including vessel formation. Elaborate coordination of Eph-and ephrin-related signaling among different cell populations is required for proper formation of the embryonic vessel network. There is growing evidence supporting the idea that Eph and ephrin proteins also have postnatal interactions with a number of other membraneassociated signal transduction pathways, coordinating translation of environmental signals into cells. This article provides an overview of membrane-bound signaling mechanisms that define vascular identity in both the embryo and the adult, focusing on Eph-and ephrin-related signaling. We also discuss the role and clinical significance of this signaling system in normal organ development, neoplasms, and vascular pathologies.

Determination of critical shear stress for maturation of human pluripotent stem cell‐derived endothelial cells towards an arterial subtype

“…The NOTCH1 pathway and chicken ovalbumin upstream promoter—transcriptional factor (COUP‐TFII) actively regulate arterial and venous specification respectively during early embryonic development. Activation of the NOTCH1 pathway leads to upregulation of the arterial marker EphrinB2, whereas COUP‐TFII activation leads to upregulation of the venous marker EphB4, imparting their unique EC identity (Cui et al, ; dela Paz & D’Amore, ; Hashimoto et al, ). Hence, we used NOTCH1 and EphrinB2 as the putative arterial markers, while COUP‐TFII and EphB4 were used as venous marker to denote the two different EC subtypes.…”

Molecular identity of arteries, veins, and lymphatics

“…41 Furthermore, Eph-B4 is located in cell surface regions called caveolae, suggesting another function as a sensor for mechanical forces. 42 Eph receptors are also activated in clusters, rather than as single receptors; 43–45 Eph receptor density can affect its function, with activation in the context of high Eph receptor density inducing cells to move away from each other, while activation in lower density promotes cell adhesion. 46…”

Arteriogenesis of the Spinal Cord—The Network Challenge

“…It is more a vivid system that might change depending on, e.g., metabolic needs, oxygen availability, oxygen radicals, and shear stress [56][57][58][59][60]. Under pathological conditions, like chronic ischemia, the identifying markers of the vessel walls change, indicating the convertibility of this biological system [61]. More specifically, enhanced shear stress might result in arteriogenesis, which establishes a biological bypass to circumvent the slowly growing stenosis of a vessel [62][63][64].…”