A Darwinian approach to the development of the vascular system in the vertebrates.

The vascular system originated around 600 million years ago. Endothelial cells evolved between 540 and 510 million years ago, and endothelial heterogeneity also developed. In invertebrates, two typologies have been described, the so-called open and closed systems, whereas in vertebrates only a closed system is present. In mammals, the presence of smooth muscle cells in the walls of small arteries regulates blood pressure and distribution to different organs; capillaries are involved in the exchange of gasses and metabolites; veins return the blood to the heart, whereas lymphatic vessels collect interstitial fluids and white blood cells and are in continuity with the venous system. Endothelial heterogeneity is the consequence of the different interactions of endothelium with the organ and tissue microenvironment including stromal cells, which is mediated by soluble factors or cell-cell/cell-extracellular matrix interactions leading to a particular phenotype of the endothelium. In this context, the heterogeneity of endothelial cells reflects specific responses to different microenvironments and their specialization to perform different functions, leading to different subsets of endothelial cells with unique gene expression patterns.