Hemodynamics, Endothelial Gene Expression, and Atherogenesis a

Vascular endothelium, the continuous lining of the cardiovascular system, forms a multifunctional interface between circulating blood and the various tissues and organs of the body. It constitutes a selectively permeable barrier for macromolecules, as well as non-thrombogenic container that actively maintains the fluidity of blood. It is a metabolically active tissue, serving as the source of multiple factors (peptides, proteins, lipids) that are critical for normal homeostasis. These include growth stimulators and inhibitors [e.g., platelet-derived growth factor, (PDGF), transforming growth factor-beta (TGF-beta), fibroblast growth factor (FGF), and heparin-like glycosaminoglycans]; vasoconstrictors and vasodilators [e.g., endothelin-1 (ET1 ), angiotensin 11, and endothelial-derived relaxing factors, such as nitric oxide]; the various proand anti-thrombotic factors (e.g., tissue factor, thrombomodulin, and von Willebrand factor); fibrinolytic activators and inhibitors (e.g., tissue plasminogen activator (tPA), urokinase, and plasminogen activator inhibitor1 , (PAIl)]; potent arachidonate metabolites (e.g., prostacyclin and PGI,); leukocyte adhesion molecules (e.g., E-Selectin, P-Selectin, ICAM-I, and VCAM-I) and multiple cytokines (e.g., IL-I, IL-6, IL-8, MCP-I, and GM-CSF). This partial list underscores the functional diversity of the endothelial interface in normal physiology and also illustrates its potential contributions to pathophysiological processes in vascular disease. It has been our laboratory's working concept that the vascular endothelium is a dynamically mutable interface, whose structural and functional properties are respon-

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