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(Circulation Research. 2006;99:666.)
© 2006 American Heart Association, Inc.

Editorials

Vascular Endothelial Growth Factor Signaling to Endothelial Nitric Oxide Synthase

More than a FLeeTing Moment

Michelle I. Lin, William C. Sessa

From the Yale School of Medicine (W.C.S., M.I.L.), Vascular Biology & Transplantation Program, Boyer Center for Molecular Medicine, New Haven, Conn.

Correspondence to William C. Sessa, Yale School of Medicine, Vascular Biology & Transplantation Program, Boyer Center for Molecular Medicine, 295 Congress Ave, New Haven, CT 06536. E-mail william.sessa@yale.edu

See related article, pages 715–722

Key Words: VEGF • receptors • NO • chimeric • angiogenesis

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

There is substantial evidence supporting the idea that the process of angiogenesis requires the synthesis of endothelium-derived nitric oxide (NO). NO, characterized as a major endothelial-derived relaxing factor, exerts paracrine and autocrine roles in maintaining cardiovascular homeostasis, vascular tone, and microvascular permeability. During the early steps of angiogenesis in which new blood vessels sprout from existing vascular beds, there is a persistence of vasodilation and increase in vascular permeability, suggesting that these hemodynamic changes in the existing vasculature are indispensable during an angiogenic process. A number of angiogenic factors can triggers the release of NO, synthesized by the endothelial isoform of NO synthase (eNOS). One such factor is the vascular endothelial growth factor (VEGF), which as its name implies, is a critical mitogenic, chemoattractant, and survival factor for endothelial cells¹ in addition to being characterized as a potent vascular permeability factor.² Early studies have demonstrated that VEGF can readily stimulate NO production in cultured cells and isolated blood vessels and that NO is essential in mediating the VEGF-induced endothelial cell proliferation and organization into tubes in 3D cultures.^3,4 Subsequent in vivo studies have also demonstrated that eNOS knockout mice had significantly attenuated VEGF and ischemia induced angiogenesis and vascular permeability.^5,6 These studies place eNOS derived NO as a key mediator of VEGF induced angiogenesis in postnatal mice.

Since the discovery of VEGF, or VEGF-A, and subsequent members of the VEGF family (VEGF-B, -C, -D, -E, and placenta growth factor, PlGF), intense research has been performed to elucidate their modes of . . . [Full Text of this Article]

Related Article:

Direct Evidence for Endothelial Vascular Endothelial Growth Factor Receptor-1 Function in Nitric Oxide–Mediated Angiogenesis

Shakil Ahmad, Peter W. Hewett, Ping Wang, Bahjat Al-Ani, Melissa Cudmore, Takeshi Fujisawa, Jody J. Haigh, Ferdinand le Noble, Ling Wang, Debabrata Mukhopadhyay, and Asif Ahmed
Circ. Res. 2006 99: 715-722. [Abstract] [Full Text] [PDF]

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