Chapter 5

### INTRODUCTION

Each and every blood vessel throughout the body is covered, at its inner, luminal surface, by a monolayer of specialized cells, i.e., the vascular endothelial cells. This monolayer represents the primary anatomical site that separates the compartment of the flowing blood from the body's interstitium. Although spread throughout the body and thus not easily discernible, all endothelial cells together cover a surface that has been estimated as 350 m2 (see Ref. 1) and may count as many as 60 trillion (6 × 1013) cells.2 The total weight of all endothelial cells has been estimated to be between 110 g3 and 750 g, or as much as the liver.4 Recent scientific evidence has made clear that the endothelium may not be less metabolically active than the liver. It was 25 years ago when the ground-breaking experimental studies discovered the crucial role of the endothelium in regulating vascular smooth muscle tone and coagulation and it was concluded that the endothelium is not merely a passive barrier.5,6,7

Endothelial cells are polygonal in shape and generally orientated along the long axis of the vessels, thereby responding to the forces that the shear of the flowing blood exerts on their surface. Endothelial cells are polarized cells, with an apical (luminal) membrane facing the blood stream and an abluminal membrane facing the intercellular space. This polarity is manifested by a distinct protein composition of the two membranes and the controlled transport of molecules along either of these membranes. Intercellular tight junctions impede intercellular diffusion of molecules between the apical and abluminal membrane.

Because of its position, the endothelium is permanently exposed to hemodynamic forces exerted by blood flow, blood pressure, and vascular wall distension. In addition to these mechanical stimuli, the endothelium receives a plethora of chemical signals, both blood-borne and tissue-derived, which may elicit endothelial responses acting on the vessel wall itself or on more distant target sites. Some of these signals play an important role in modifying the primary function of the endothelium, that is, the precise control of the passage of solutes, macromolecules, and blood cells across the vascular wall.

### ANATOMICAL FEATURES OF THE ENDOTHELIUM IN DIFFERENT VASCULAR SEGMENTS

Morphologically, endothelial cells are flat cells that usually spread out broadly on the inner surface of a blood vessel; the nucleus can be prominently seen on microscopic images, protruding into the lumen (Figure 5-1). However, endothelial cells from different vascular beds vary considerably in phenotype. Thus, in different areas of the circulatory system, the endothelium is characterized by anatomically distinct features, which allow it to adapt to the varying regulatory functions of different organs. Depending on the presence of intercellular junctions, endothelia can be classified as "continuous," "fenestrated," or "discontinuous." For example, in the brain a continuous endothelial monolayer is part of the blood–brain barrier,8 whereas in the ...

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