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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:10.)
© 2006 American Heart Association, Inc.

Editorials

Tightening the Barrier

Mechanical Forces and the Control of Endothelial Permeability

Jeremy D. Pearson

From King’s College London, Cardiovascular Division, Guy’s Campus, London.

Correspondence to Jeremy D. Pearson, King’s College London, Cardiovascular Division, Guy’s Campus, London SE1 1UL. Email jeremy.pearson@kcl.ac.uk

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Interendothelial junctional clefts have long been supposed to be the major sites at which water and solutes leave the vessel lumen (except in vessels with fenestrated or discontinuous endothelium) to reach extravascular tissue. Pioneering electron microscopy studies by Palade with the Simionescus demonstrated this phenomenon directly, showing that proteins of a molecular diameter up to &20 Å could permeate these clefts in capillaries, and rather larger proteins could do so in post-capillary venules. They were also the first, by usng freeze fracture techniques, to show that the extent and complexity of the arrangement of interendothelial junctional proteins varied substantially across the vasculature, in a manner consistent with what was known about vessel permeability: the most complex and extensive junctions are found in arteries and in the small vessels forming the blood-brain barrier, whereas the least complex and extensive are found in post-capillary venules.^1–3 However, at that time neither the identity of the major molecular components of the junctions was known nor had anyone begun to consider what mechanisms might lead to this graded variation of endothelial phenotype.

See page 62

Nonetheless, the distinctive shapes of endothelial cells in situ according to their position in the vascular tree suggests their ability to respond to physical forces such as shear stress—an insight usually attributed to Virchow, who described the variation in endothelial cell morphology and proposed it more than 150 years ago. Direct confirmation came only in the 1970s from observations of the endothelium in grafted vessels in vivo and in the . . . [Full Text of this Article]

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