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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1004.)
© 2007 American Heart Association, Inc.

Brief Reviews

Physiological Roles of Vascular Nucleoside Transporters

Michaela Löffler; Julio C. Morote-Garcia; Shelley A. Eltzschig; Imogen R. Coe; Holger K. Eltzschig

From the Department of Anesthesiology and Intensive Care Medicine (M.L., J.C.M.-G., S.A.E., H.K.E.), Tübingen University Hospital, Tübingen, Germany; Department of Biology (I.R.C.), York University, Toronto, Canada.

Correspondence to Holger K. Eltzschig, MD, PhD, Assistant Professor of Anesthesiology, Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Waldhörnle Str. 22, 72072, Tübingen, Germany. E-mail heltzschig{at}partners.org

Nucleoside transporters (NTs) comprise 2 widely expressed families, the equilibrative nucleoside transporters (diffusion-limited channels) and concentrative nucleoside transporters (sodium-dependent transporters). Because of their anatomic position at the blood-tissue interface, vascular NTs are in an ideal position to influence vascular nucleoside levels, particularly adenosine, which among others plays an important role in tissue protection during acute injury. For example, endothelial NTs contribute to preserving the vascular integrity during conditions of limited oxygen availability (hypoxia). Indeed, hypoxia-inducible factor-1-dependent repression of NTs results in enhanced extracellular adenosine signaling and thus attenuates hypoxia-associated increases in vascular leakage. In addition, vascular NTs also contribute to cardiac ischemic preconditioning, coronary vasodilation, and inhibition of platelet aggregation. Moreover, vascular nucleoside uptake via NTs is important for nucleoside recovery, particularly in cells lacking de novo nucleotide synthesis pathways (erythrocytes, leukocytes). Taken together, vascular NTs are critical in modulating adenosine-mediated responses during conditions such as inflammation or hypoxia.

Changes in vascular NT expression or function result in changes of extracellular nucleoside levels, thereby directly modulating vascular adenosine signaling. Therefore, vascular NT functions are involved in multiple innate adaptive pathways of the vasculature including modulation of barrier function, acute inflammation, vascular tone, ischemic preconditioning, or platelet aggregation.

Key Words: adenosine signaling • concentrative nucleoside transporter • endothelial barrier • equilibrative nucleoside transporter • hypoxia • inflammation • ischemia • preconditioning

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