The Endothelium as an Input Output Device

Much of endothelial cell biology can be understood—at least conceptually—by considering each and every endothelial cell in the body as an adaptive input-output device (Figure 1). The input arises from the extracellular milieu and may include biochemical or biomechanical signals. The output is manifested as the cellular phenotype and includes a number of structural and functional properties. Some of these properties are expressed at the level of individual cells or cell culture (e.g., protein, mRNA, proliferation, apopto-sis, migration, and permeability), whereas other properties are expressed at higher levels of organization—for example the blood vessel (e.g., leukocyte trafficking, vasomotor tone, fibrin deposition) or organism (e.g., redistribution of blood flow, vascular bed-specific phenotypes). Each endothelial cell may have unique intrinsic properties, the so-called set point. Differences in set point are brought about by environmentally induced epigenetic changes in the "hard wiring" of the cell (see later discussion). Differences in signal input and set point conspire to generate phenotypic differences in space and time—a phenomenon known as endothelial cell heterogeneity or vascular diversity.

If one accepts the analogy of each endothelial cell representing its own input-output device, it is not a stretch to consider the endothelium as a circuit board—one that is hard wired (to some extent) to meet the demands of the tissue, and one that is highly vulnerable to short-circuiting as a mechanism of vasculopathic disease. There are important caveats to this model. First, the input-output device is not a black box, but rather a multiorganelle cell with highly complex nonlinear signaling networks. Second, the system displays properties of emergence. In other words, while the individual capillary endothelial cell follows simple local rules and at any point in time and space has a definable


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Essentials of Human Physiology

Essentials of Human Physiology

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