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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:6.)
© 2008 American Heart Association, Inc.

Editorials

Twin Layers of Lightning

A New Role for the Chaperone Hsp90 in Angiogenesis

Xinchun Pi; Cam Patterson

From the Carolina Cardiovascular Biology Center (X.P., C.P.) and the Division of Cardiology (C.P.), University of North Carolina, Chapel Hill.

Correspondence to Cam Patterson, MD, Director, Division of Cardiology, and Carolina Cardiovascular Biology Center, University of North Carolina at Chapel Hill, 8200 Medical Biomolecular Research Building, Chapel Hill, NC 27599-7126. E-mail cpatters@med.unc.edu

Key Words: Hsp90 • VEGF • migration

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

Blood vessel formation occurs through two sequential mechanisms: the de novo formation of blood vessels during embryonic development (vasculogenesis) and the formation of new capillaries from preexisting vessels (angiogenesis). The principle mechanism of vessel formation in adults is angiogenesis and malfunction of this process leads to a wide range of diseases including tumors, inflammatory diseases, psoriasis, rheumatoid arthritis, and diabetic retinopathy, presciently and collectively referred to as "angiogenesis-dependent diseases."¹ Most embryonic vessels and proliferating endothelial cells during angiogenesis are under control of a key molecule, vascular endothelial growth factor (VEGF). More than 10 new drugs targeting VEGF have been approved since 2004 by the Food and Drug Administration in the United States for the treatment of cancer and age-related macular degeneration, but it remains to be determined what the ultimate therapeutic success of those angiogenic inhibitors will be. It is generally accepted that VEGF-dependent endothelial cell migration is required for angiogenic responses; however, specific roles for VEGF-enhanced cell motility have been incompletely characterized.

See page 105

To fill this gap, a report published in this issue of Arteriosclerosis, Thrombosis, and Vascular Biology² illuminates a critical role for the 90-kDa heat-shock protein (Hsp90) in VEGF-stimulated endothelial migration. Specifically, Miao and colleagues designed a dominant-negative Hsp90 construct (D88N-Hsp90β), cleverly based on a bioinformatic comparison of ATP-binding domain sequences of Hsp82 in yeast with Hsp90 and β isoforms in mammalian cells. They demonstrate that D88N-Hsp90β potently inhibits VEGF-stimulated Akt and eNOS activation, which are critical modulators of VEGF-induced cell migration and angiogenesis. This . . . [Full Text of this Article]

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Dominant-Negative Hsp90 Reduces VEGF-Stimulated Nitric Oxide Release and Migration in Endothelial Cells

Robert Q. Miao, Jason Fontana, David Fulton, Michelle I. Lin, Kenneth D. Harrison, and William C. Sessa
Arterioscler Thromb Vasc Biol 2008 28: 105-111. [Abstract] [Full Text] [PDF]

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