Summary
In the developing embryo, the vasculature first takes the form of a web-like network
called the vascular plexus. Arterial and venous differentiation is subsequently guided
by the specific expression of genes in the endothelial cells that provide spatial
and temporal cues for development. Notch1/4, Notch ligand delta-like 4 (Dll4), and
Notch downstream effectors are typically expressed in arterial cells along with EphrinB2,
whereas chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and
EphB4 characterise vein endothelial cells. Haemodynamic forces (blood pressure and
blood flow) also contribute importantly to vascular remodelling. Early arteriovenous
differentiation and local blood flow may hold the key to future inflammatory diseases.
Indeed, despite the fact that atherosclerosis risk factors such as smoking, hypertension,
hypercholesterolaemia, and diabetes all induce endothelial cell dysfunction throughout
the vasculature, plaques develop only in arteries, and they localise essentially in
vessel branch points, curvatures and bifurcations, where blood flow (and consequently
shear stress) is low or oscillatory. Arterial segments exposed to high blood flow
(and high laminar shear stress) tend to remain plaque-free. These observations have
led many to investigate what particular properties of arterial or venous endothelial
cells confer susceptibility or protection from plaque formation, and how that might
interact with a particular shear stress environment.
Keywords
Shear stress - endothelial cells - arteriovenous differentiation - atherosclerosis