One of the least considered aspects of vascular biology is vascular evolution and the clues it may hold to understanding endothelial function and pathology. Comparative problems between species are encountered on a regular basis when using laboratory animals and cultured endothelial cells (ECs) to model human conditions. Further complicating these problems is the endothelial heterogeneity found within those animal models and within humans. The evolutionary process underlies the marvelous diversities among vascular systems both within an organism and across the animal kingdom. But that same evolutionary process has generated the abundance of technical problems and complexities that are necessary to resolve as practical matters in research and medicine. The resolution of these problems lies in understanding the fundamental physiological and biochemical nature of comparative vascular biology and the subsequent application of that knowledge to human pathologies. Thus, understanding the origins of the vascular system is a vital component for the resolution of human vasculopathies.

Evolution is a biological fact; much the same as gravity or electromagnetism are physical facts. Fundamental evolutionary forces, such as mutagenesis and natural selection, are scientifically, qualitatively observed and quantitatively measured on a regular basis. The application of those evolutionary forces to the endothelium and vascular development provides a model (Figure 4.1) that correlates vascular specialization and complexity with larger or more complex organisms. Further consideration of these evolutionary trends in a developmental context leads to “Evo Devo” constructions. These reveal tissue perfusion as a basic need leading to the adaptations in vascular evolution.