It is critical to note that not all of the vasculature shares a common embryologic source and that a variety of signaling pathways ultimately determine whether early vessel precursors (angioblasts) become veins or arteries. If angioblasts are exposed to vascular endothelial growth factor and subsequently experience activation of membrane-bound Notch receptors (which play a role in development of most vertebrate organs), development moves in an arterial direction. The absence of Notch activation and, alternatively, engagement of COUP-TFII leads to venous development. Ultimately, arteries develop into elastic conducting vessels (aorta and proximal primary branches), and the more distal vessels become muscular resistance conduits.
Diversity within the vascular tree is profound for vessels of all calibers. For example, it would be incorrect to assume that the vascular tube we call the aorta is the same throughout its length. Indeed, it is quite different. It was already noted that the vascular smooth muscle cells (VSMCs) of the root and arch have different embryological origins, and perhaps related to this are known differences in “tube” diameter, wall thickness, elasticity (reduced from proximal to distal), and collagen content (increased proximal to distal). It is also known that proximal and distal aortic VSMCs differ in their ex-vivo response to cytokine stimulation.1
Most relevant to clinicians are whether and how such differences affect disease susceptibility. Aortic arch aneurysms are principally due to cystic medial degeneration, whereas abdominal aortic aneurysms are almost exclusively due to atherosclerosis. This observation has fascinated students of vascular biology, including surgeons and vascular geneticists, who have discovered that approximately 17% of the expressed genome in the proximal versus distal aorta is distinct.2 This is a likely basis for differences in biologic behavior, including responses to both internal and external stimuli. Might these differences in gene expression play a role in aneurysm formation due to aortitis? These aneurysms are far more common in the aortic arch either as an isolated finding or as part of giant cell arteritis or Takayasu arteritis.
Can a similar case for vascular diversity be made in reference to the territories of small vessels? Indeed, it can. In attempting to demonstrate unique qualities of microvascular beds, embryologists and vascular biologists have noted that endothelial cell (EC) gene expression and proteins produced by ECs are as unique as the different organs they perfuse.3,4 In animal studies, transfer of ECs from one organ to another is associated with either EC death or development of abnormal EC characteristics.
