Endothelial cells in physiology and in the pathophysiology of vascular disorders

DB Cines, ES Pollak, CA Buck… - Blood, The Journal …, 1998 - ashpublications.org
DB Cines, ES Pollak, CA Buck, J Loscalzo, GA Zimmerman, RP McEver, JS Pober, TM Wick
Blood, The Journal of the American Society of Hematology, 1998ashpublications.org
PART I THE ENDOTHELIUM has long been viewed as an inert cellophane-like membrane
that lines the circulatory system with its primary essential function being the maintenance of
vessel wall permeability. Shortly after the first description of circulating blood by William
Harvey in 1628, the existence of a network of vessels arose from studies of Malphigi, who
described the physical separation between blood and tissue. 1 In the 1800s, von
Reckingausen established that vessels were not merely tunnels bored through tissues but …
PART I THE ENDOTHELIUM has long been viewed as an inert cellophane-like membrane that lines the circulatory system with its primary essential function being the maintenance of vessel wall permeability. Shortly after the first description of circulating blood by William Harvey in 1628, the existence of a network of vessels arose from studies of Malphigi, who described the physical separation between blood and tissue. 1 In the 1800s, von Reckingausen established that vessels were not merely tunnels bored through tissues but were lined by cells. The strength of Starling’s experiments and his law of capillary exchange proposed in 1896 served to solidify the belief that the endothelium was principally a selective but static physical barrier, not withstanding Heidenhahn’s description in 1891 of the endothelium as an active secretory cell system. However, electron microscopic studies of the vessel wall by Palade in 1953 and physiological studies by Gowan in 1959 describing the interaction between lymphocytes and endothelium of postcapillary venules stimulated numerous subsequent studies that led to the current view of the endothelium as a dynamic, heterogeneous, disseminated organ that possesses vital secretory, synthetic, metabolic, and immunologic functions. 1 The endothelial cell (EC) surface in an adult human is composed of approximately 1 to 6 1013 cells, weighs approximately 1 kg, and covers a surface area of approximately 1to7m2. 2 ECs line vessels in every organ system and regulate the flow of nutrient substances, diverse biologically active molecules, and the blood cells themselves. This gate-keeping role of endothelium is effected through the presence of membrane-bound receptors for numerous molecules including proteins (eg, growth factors, coagulant, and anticoagulant proteins), lipid transporting particle (eg, low-density lipoprotein [LDL]), metabolites (eg, nitrous oxide and serotonin), and hormones (eg, endothelin-1), as well as through specific junctional proteins and receptors that govern cell-cell and cellmatrix interactions.
The endothelium also plays a pivotal role in regulating blood flow. In part, this results from the capacity of quiescent ECs to generate an active antithrombotic surface that facilitates transit of plasma and cellular constituents throughout the vasculature. Perturbations, such as those that may occur at sites of inflamma-
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