Am J Cardiovasc Dis 2011;1(3):200-213

Review Article
Hyaluronan regulation of vascular integrity

Frances E. Lennon, Patrick A. Singleton

Department of Medicine, Section of Pulmonary and Critical Care, and Department of Anesthesia and Critical Care, Pritzker
School of Medicine, The University of Chicago, Chicago, IL 60637

Received July 5, 2011; accepted July 16, 2011; Epub September 10, 2011; published September 30, 2011

Abstract: Vascular integrity or the maintenance of blood vessel continuity is a fundamental process regulated, in part, by
the endothelial glycocalyx and cell-cell junctions. Defects in endothelial barrier function are an initiating factor in several
disease processes including atherosclerosis, ischemia/reperfusion, tumor angiogenesis, cancer metastasis,
diabetes, sepsis and acute lung injury. The glycosaminoglycan, hyaluronan (HA), maintains vascular integrity through
endothelial glycocalyx modulation, caveolin-enriched microdomain regulation and interaction with endothelial HA binding
proteins. Certain disease states increase hyaluronidase activity and reactive oxygen species (ROS) generation which
break down high molecular weight HA to low molecular weight fragments causing damage to the endothelial glycocalyx.
Further, these HA fragments can activate specific HA binding proteins upregulated in vascular disease to promote
actin cytoskeletal reorganization and inhibition of endothelial cell-cell contacts. This review focuses on the crucial role of HA
in vascular integrity and how HA degradation promotes vascular barrier disruption. (AJCD1107003).

Keywords: Endothelial permeability, glycocalyx, caveolin-enriched microdomain, actin cytoskeleton, CD44, HABP2,
versican, TLR2, TLR4, caveolin-1

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The University of Chicago School of Medicine
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