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(Circulation Research. 2008;103:229.)
© 2008 American Heart Association, Inc.

Editorials

Fine-Tuning the Angiogenic Response to Vascular Endothelial Growth Factor

James K. Liao

From the Vascular Medicine Research Unit, Cardiovascular Division, Brigham & Women’s Hospital and Harvard Medical School, Boston, Mass.

Correspondence to James K. Liao, MD, Brigham & Women’s Hospital, 65 Landsdowne St, Room 275, Cambridge, MA 02139. E-mail jliao@rics.bwh.harvard.edu

See related article, pages 261–268

Key Words: VEGF • angiogenesis • protein kinase Akt • ischemia

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

Vascular endothelial growth factor (VEGF) is an important mediator of vascular development and postnatal angiogenesis.^1,2 Homozygous deletion of VEGF gene leads to impaired vascular formation and early embryonic lethality.³ Interestingly, deletion of just one VEGF allele is sufficient to produce similar vascular abnormalities,^3,4 suggesting that the strength and integrity of the VEGF signaling pathway are critical for the spatial–temporal formation of blood vessels in utero. These actions of VEGF are mediated predominantly by 2 tyrosine kinase receptors: VEGFR-1 (flt-1) and VEGFR-2 (flk-1/KDR).⁵ Mice with homozygous mutations that inactivate either receptor die in utero with a similar phenotype as mice with VEGF deletion, indicating that both receptors are obligatory for the function of VEGF.^1,6 Although the vascular phenotype between these VEGFR mutant mice are overlapping to some degree, they do differ in terms of showing that VEGFR-2 plays a greater role in vascular organization,⁷ whereas VEGFR-1 appears to be more important in mediating hemangioblast commitment and endothelial cell replication.⁸ Nevertheless, both VEGFR-1 and VEGFR-2 are essential in coordinating endothelial cell assembly and vascular formation during embryonic development.

The upregulation of VEGF is also necessary for physiological and pathological neovascularization in response to hypoxia and for tumor growth.^9,10 The precise role of VEGFR-1 and VEGFR-2 in mediating the postnatal angiogenic response to VEGF, however, is less well understood and, in some cases, somewhat controversial. For example, most, if not all, of the angiogenic response to VEGF is mediated through VEGFR-2⁷ rather than VEGFR-1 because mutant mice lacking the tyrosine kinase domain of . . . [Full Text of this Article]