© 1998 American Heart Association, Inc.
Editorial |
Vascular Endothelial Growth Factor and the Angiopoietins
Working Together to Build a Better Blood Vessel
Correspondence to Kevin G. Peters, MD, Duke University Medical Center, Research Drive, Box 3623, Durham, NC 27710. E-mail kgpet@duke.edu
Key Words: angiogenesis • endothelium • angiopoietin • collateral vessel • Tie2
Angiogenesis is a complex multistep process by which new blood vessels are formed from the preexisting vasculature.1 2 Angiogenesis is a crucial event in normal embryonic development, and it contributes to the development and progression of a number of diseases, including cancer, arthritis, and diabetes. Conversely, insufficient growth of collateral vessels is a major clinical problem in atherosclerotic cardiovascular disease. The involvement of angiogenesis, or the failure of angiogenesis, in these important diseases has created a tremendous effort to define the molecular mechanisms by which the process is driven.
Until recently, most of the work in the field has focused on
polypeptide growth factors, such as fibroblast growth factor and
vascular endothelial growth factor (VEGF), which are
mitogenic for endothelial cells in vitro
and produce an angiogenic response in vivo. Angiopoietins (Ang1 and
Ang2) constitute a novel family of endothelial growth
factors that are ligands for the endothelium-specific
receptor tyrosine kinase, Tie2.3 Unlike other
endothelial growth factors, stimulating Tie2 in
cultured endothelial cells with either Ang1 or Ang2
does not produce a mitogenic response.3
Similar to other angiogenic factors, however, Ang1 can stimulate
endothelial sprouting in vitro.4
Complicating matters, Ang2 appears to block the activation of Tie2 by
Ang1, suggesting that it may be a naturally occurring
inhibitor of Ang1/Tie2 activity.5 Despite the
inability of angiopoietins to stimulate endothelial
mitogenesis, disrupting the function of either Tie2 or Ang1 in
transgenic mice resulted in early embryonic lethality secondary to
defects in the developing vasculature.6 7 8 The defects
included a decreased number of endothelial
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