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(Circulation Research. 2003;92:586.)
© 2003 American Heart Association, Inc.

Editorials

Tie-ing the Antiinflammatory Effect of Angiopoietin-1 to Inhibition of NF-B

Byeong Hwa Jeon, Firdous Khanday, Shailesh Deshpande, Azeb Haile, Michitaka Ozaki, Kaikobad Irani

From the Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Md.

Correspondence to Kaikobad Irani, The Johns Hopkins University School of Medicine, Ross 1023, 720 Rutland Ave, Baltimore, MD 21205. E-mail kirani@jhmi.edu

Key Words: angiopoietin-1 • Tie2 • nuclear factor-B • endothelial cells • ABIN-2

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

Activation of the vascular endothelium occurs in many clinical scenarios such as inflammatory or infectious conditions (sepsis), reperfusion injury, and transplant graft rejection.^1–5 Under such circumstances, endothelial activation is primarily induced by cytokines such as tumor necrosis factor (TNF) and interleukin-1ß (IL-1ß) and vascular permeability factors such as vascular endothelial growth factor (VEGF) that upregulate a number of genes including prothrombotic factors, chemokines, and cell adhesion molecules, many of which are dependent on the action of the pleiotropic transcription factor nuclear factor-B (NF-B).^2,6–11 Activated endothelium is compromised in its structural and functional integrity, leading to transmigration of leukocytes into the vessel wall, plasma leakage, and thrombosis.

Angiopoeitin-1 (Ang1) is a vasculogenic factor that induces endothelial cell sprouting, migration, and network formation,^12–15 coordinated processes that are crucial in the development of new blood vessels. Angiopoietins signal via the Tie (tyrosine kinase with immunoglobulin and epidermal growth factor homology domains) family of receptor tyrosine kinases, of which Tie2 is endothelial-cell specific. In addition to its important role in vasculogenesis, Ang1, through Tie2, suppresses activation of endothelial cells as evidenced by its inhibition of vascular cell adhesion molecules and procoagulant tissue factor expression.^16,17 These effects confer on Ang1 potent antiinflammatory properties.^18–20 Although Ang1 affects the expression of many NF-B–responsive genes, a functional and mechanistic link between Ang1 and NF-B signaling has not been previously shown.

The report by Hughes et al²¹ in this issue of Circulation Research provides the first demonstration that the mitigating effect . . . [Full Text of this Article]

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