Proximate and evolutionary causation of endothelial heterogeneity

Endothelial phenotypes display remarkable heterogeneity in structure and function, in time and space, and in health and disease. As a biological trait, phenotypic heterogeneity has evolutionary and proximate explanations. Here we introduce concepts of evolutionary biology, evolutionary developmental biology, developmental plasticity, and homeostasis toward understanding mechanisms of endothelial heterogeneity. We conclude that endothelial heterogeneity arises from a complex interplay between the genome and the environment, operating at both population and organismal levels across a broad spectrum of time. Mismatch between the genome and/or epigenome and the environment is an important determinant of human vascular disease.