If the endothelium were to be considered an organ, it would be without a doubt the largest, with its 6 trillion cells, area of 5000m2, and 1kg weight. With knowledge of the endothelium stemming back to the early 1600s with William Harvey’s work on the circulation as a closed circuit with a pump and Marcello Malpighi’s observations of blood capillaries, the focus over the next 400 years was mainly on the pump itself, leading to the creation of a major clinical field – cardiology. Although scientists were aware of blood vessels and their role in circulation, it wasn’t until the early 1960s that the endothelium was able to be seen with electron microscopy and therefore be differentiated and characterized.1 The recognition of endothelial cells with diverse structures and functions led to an overwhelming increase in research and interest in this field, and it is now well-established that endothelial cells make up a rather active cell layer, and are highly adapted to their microenvironment. In particular, a specific growth factor VEGF has been found to be unquestionably relevant to nearly all endothelial disorders.
Role and Classification of the Endothelium
It is widely known that the endothelium plays a role in nearly every disease state ranging from cancers in hematology-oncology and sepsis in infectious disease to hepatitis and strokes, in gastroenterology and neurology, respectively. Consequently, one cannot rely solely on the mechanisms an endothelial cell from one location as a model and predictor of structure and function of another, as it is recognized that there are a diverse amount of phenotypes, each differing from one another.2 As “endotheliology” is not a recognized clinical discipline, most knowledge concerning the endothelium has been obtained from research of its microenvironment by specialists in their respective fields. Hematologists are all-too aware of the role of the endothelium in atherosclerosis, while hepatologists recognize the important of sinusoidal endothelial cells for liver regeneration. The uniqueness of the endothelium coupled with the difficulties caused by a lack of a clinical field has lead to a series of unforeseen and surprising discoveries.
The simple classification of the endothelial cells themselves pose challenges. The endothelium is, anatomically speaking, the inner lining of the blood and lymphatic vessels.3 However, many characteristic structures such as fenestrae are not present on every endothelial cell, and other features, e.g. caveolae, are not specific to the endothelium. There are also other cells that form the inner lining of the blood vessels, and therefore molecular markers are instead being used to differentiate. Furthermore, endothelial cells arise from the mesoderm via hemangioblasts, however they may differentiate instead into hematopoietic stem cells, and the endothelial progenitors may themselves differentiate into other cell lineages. Due to these difficulties endothelial...