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(Circulation Research. 2007;101:10.)
© 2007 American Heart Association, Inc.

Editorials

Endothelial Mechanisms of Flow-Mediated Athero-Protection and Susceptibility

Peter F. Davies

From the Institute for Medicine and Engineering, and Departments of Pathology and Laboratory Medicine, and Bioengineering, University of Pennsylvania.

Correspondence to Peter F. Davies, PhD, University of Pennsylvania, 1010 Vagelos Laboratories, 3340 Smith Walk, Philadelphia, PA 19104-6383. E-mail pfd@pobox.upenn.edu

See related article, pages 97–105

Key Words: endothelium • hemodynamics • flow characteristics • athero-susceptibility • PKC • TNF-, caspase • endothelial apoptosis

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

The arterial endothelium survives remarkably well as the interface between blood and vessel wall in an environment of constantly changing biomechanical stresses as well as acute and chronic exposure to inflammatory stimulants (eg, cytokines and hypercholesterolemia respectively).¹ Cell turnover, which tends to occur in regional clusters,² is otherwise very low in this monolayer. The endothelium also plays an important regulatory role in the pathogenesis of vascular disease. The cells readily respond to diverse stimuli through a repertoire of mechanisms to enhance their own survival even as they facilitate inflammatory, proatherogenic responses in the subendothelial tissue. The necessity to be a responsive cellular interface probably accounts for much of the endothelial phenotype heterogeneity that exists between vascular beds as well as within discrete regions of the arterial circulation.^3,4

Hemodynamic characteristics that vary with blood vessel geometry predict the location of arterial sites that are susceptible to atherosclerosis.⁵ Curved and branching vessel geometries create sites of flow separation that contain transient flow reversals, lower average shear stresses, and occasional turbulence, (collectively, disturbed flow) and that are predictive of lesion formation. In contrast, pulsatile unidirectional laminar flow (and higher average shear stresses) is associated with regions where atherosclerosis rarely occurs, despite there being equivalent exposure to plasma risk factors such as hypercholesterolemia throughout the circulation. Although the signatures of endothelial phenotype in such regions in vivo are varied and complex, data are emerging from genomic^5–7 and protein⁸ analyses of endothelium at such sites that identify molecular differences. Some of these are accessible for . . . [Full Text of this Article]

Related Article:

Flow Antagonizes TNF- Signaling in Endothelial Cells by Inhibiting Caspase-Dependent PKC Processing

Gwenaele Garin, Jun-ichi Abe, Amy Mohan, Weimin Lu, Chen Yan, Andrew C. Newby, Arshad Rhaman, and Bradford C. Berk
Circ. Res. 2007 101: 97-105. [Abstract] [Full Text] [PDF]

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