Evolution can be viewed as a gradual accumulation of adaptive mutations against a background of neutral change. Intraspecific diversity may be the substrate of evolution, but intraorganismal diversity – the emergence of new proteins, new cell types, and new tissue functionalities – is its exquisite product. Each organism, indeed each organ, is a complex, interlocking “bundle of adaptations.” The endothelium is no exception. Over the last three decades, the notion that the endothelium represents an uncomplicated permeability-selective barrier between blood and interstitium has been revised considerably. Endothelial cells (ECs) are now known to regulate inflammation, hemostasis, vasomotor tone, growth and proliferation of other cells, antigen presentation, extravasation of immune cells, and metabolism of tissue- or blood-derived hormones. These functions are differentially regulated in space and time (reviewed in 1). Endothelial cell heterogeneity reflects the capacity of the endothelium to adapt and respond to the unique demands of the underlying tissue (reviewed in 2). An important goal is to dissect the complex molecular mechanisms underlying endothelial cell function and dysfunction.

THE CALL FOR AN EVOLUTIONARY APPROACH

Why study comparative and evolutionary vascular biology? First, evolution is at heart an historical science, and curiosity drives us to understand the narrative of biological change as well as patterns that may underlie this change. Second, the study of simple models has for centuries been an indispensable tool for sharpening our analysis of more complex biological systems. One is reminded of the contributions of Mendel on Pisum sativum, Morgan on Drosophila melanogaster, and Kandel on Aplysia californica.