The endothelium is only now beginning to gain acceptance as a physiologically relevant organ with potential clinical significance. Yet the cell layer called the endothelium was first identified well over a century ago. In this chapter, we explore the circumstances leading to the slow recognition of the endothelium as a system with untapped diagnostic and therapeutic potential. We trace historically important steps toward increased interest in the endothelium, beginning with ancient discussions of the heart and blood vessels, and the conviction that blood derives from nutrition and is continually used up by the body. We see that, in Western medicine, the dominant culture of the Catholic Church impeded new discovery and instead emphasized reliance on accepted ideas for nearly 1,500 years. Only in the context of the Scientific Revolution of the seventeenth century could anatomists such as William Harvey challenge prevailing dogma and reach the conclusion that blood circulates and that it does so through a system of connected vascular vessels.

In this chapter, we examine those contributions and the developments that followed, slowly and gradually, the rise of new technologies for observation and the framing of new questions. We ask what caused researchers to focus on cells and tissues, and then, during the last part of the nineteenth century, to identify endothelial cells (ECs) as a unique structure, distinguishable structurally, physiologically, and developmentally from the epithelium that researchers initially had seen as closely connected to it. Then, we explore what implications the identification and naming of this particular set of cells had for the biomedical sciences.