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Journal ArticleDOI

Angiopoietin-2, a Natural Antagonist for Tie2 That Disrupts in vivo Angiogenesis

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TLDR
The discovery of a negative regulator acting on Tie2 emphasizes the need for exquisite regulation of this angiogenic receptor system.
Abstract
Angiogenesis is thought to depend on a precise balance of positive and negative regulation. Angiopoietin-1 (Ang1) is an angiogenic factor that signals through the endothelial cell-specific Tie2 receptor tyrosine kinase. Like vascular endothelial growth factor, Ang1 is essential for normal vascular development in the mouse. An Ang1 relative, termed angiopoietin-2 (Ang2), was identified by homology screening and shown to be a naturally occurring antagonist for Ang1 and Tie2. Transgenic overexpression of Ang2 disrupts blood vessel formation in the mouse embryo. In adult mice and humans, Ang2 is expressed only at sites of vascular remodeling. Natural antagonists for vertebrate receptor tyrosine kinases are atypical; thus, the discovery of a negative regulator acting on Tie2 emphasizes the need for exquisite regulation of this angiogenic receptor system.

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Angiogenesis in health and disease.

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Vascular-specific growth factors and blood vessel formation

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References
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Journal ArticleDOI

Angiogenesis in cancer, vascular, rheumatoid and other disease

TL;DR: Think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood vessel growth, which may dictate whether a primary tumour grows rapidly or slowly and whether metastases grow at all.
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Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis

TL;DR: The work from the authors' laboratories reviewed herein was supported by grants from the National Cancer Institute.
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Mechanisms of angiogenesis

TL;DR: Understanding of the molecular basis underlying angiogenesis, particularly from the study of mice lacking some of the signalling systems involved, has greatly improved, and may suggest new approaches for treating conditions such as cancer that depend onAngiogenesis.
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Requisite Role of Angiopoietin-1, a Ligand for the TIE2 Receptor, during Embryonic Angiogenesis

TL;DR: It is shown that mice engineered to lack Angiopoietin-1 display angiogenic deficits reminiscent of those previously seen in mice lacking TIE2, demonstrating that AngiopOietIn-1 is a primary physiologic ligand for TIE1 and that it has critical in vivo angiogenesis actions that are distinct from VEGF and that are not reflected in the classic in vitro assays used to characterize VEGf.
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