Microvascular remodeling: a complex continuum spanning angiogenesis to arteriogenesis

Angiogenesis, the arterialization of capillaries, and arteriogenesis are specific manifestations of the complex continuum of blood vessel-remodeling processes that are produced by environmental stimuli. Together, they determine the integrative control of vascular assembly and pattern formation. Vascular assembly and pattern formation are critical elements of therapeutic vascular collateralization of progressively ischemic organs and in the tissue engineering or organogenesis of various tissue substitutes. An integrative systems approach is useful to measure the dynamics of vascular assembly in vivo across time scales from the embryo to the adult, and spanning spatial scales from cells to whole networks, to understand the complex interplay of multiple interacting cells and signal molecules. This requires in vivo observations, multiscale computer simulations, and tools for the genetic regulation of cell interactions. The new view of vascular remodeling as a continuum that can be manipulated in various tissues and in different size blood vessels, using appropriately coordinated multisignal stimuli, should open new therapeutic avenues.