BLOOD VESSELS ARE organized in a hierarchical fashion to deliver oxygen, soluble factors, and various types of cells to all tissues in our body in a carefully regulated manner. The vascular network forms by both vasculogenesis (de novo vessel formation from angioblastic stem cells) and angiogenesis (sprouting from existing vessels).(1–3) Both processes are essential during skeletal embryogenesis or repair, but otherwise represent pathological events linked to adverse consequences.

The endothelium is one of the most important components of the vasculature, not only because it functions as an essential barrier that limits the movement of cells and molecules between the circulation and tissues, but also because it is a dynamic organ actively capable of directly communicating in a rich language with adjacent tissue and circulating blood cells. This appears evident when considering the remarkable heterogeneity of endothelial cells and their vessel size-specific, tissue-specific, and age-specific differences.(4, 5) What is the underlying cause of endothelial diversity? Certainly during development and ongoing tissue maintenance in the adult, circulatory and tissue components must continually communicate with endothelial cells.(5) However, the signaling between cells and endothelium within a tissue is, in fact, bidirectional, and endothelial cells just as readily communicate with surrounding cells through a host of humoral and growth factors, cytokines and chemokines, reactive metabolites, and polarized surface-associated molecules.(5)