Biological characterization of angiopoietin‐3 and angiopoietin‐4

  title={Biological characterization of angiopoietin‐3 and angiopoietin‐4},
  author={Hyuek Jong Lee and Chung-Hyun Cho and Su-Jeong Hwang and Han-Ho Choi and Kyung-Tae Kim and So Young Ahn and Ju-Hyun Kim and Jong-Lark Oh and Gyun Min Lee and Gou Young Koh},
  journal={The FASEB Journal},
  pages={1200 - 1208}
  • H. Lee, C. Cho, G. Koh
  • Published 1 August 2004
  • Biology, Chemistry
  • The FASEB Journal
The angiopoietin (Ang) family of growth factors includes Ang1, Ang2, Ang3, and Ang4, all of which bind to the endothelial receptor tyrosine kinase Tie2. Ang3 (mouse) and Ang4 (human) are interspecies orthologs. In experiments with human endothelial cell lines, Ang3 was identified as an antagonist of Tie2 and Ang4 was identified as an agonist of Tie2. However, the biological roles of Ang3 and Ang4 are unknown. We examined the biological effect of recombinant Ang3 and Ang4 proteins in primary… 
Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology
The activity of Ang2 on blood and lymphatic endothelial cells, its significance in human physiology and disease, and a current view of the molecular signaling pathways regulated by Ang2 in endothelium cells are summarized.
Angiopoietins and Tie Receptors
The angiopoietin-Tie signalling pathway may be a therapeutically useful target in the treatment of a number of diseases, including oedema, endotoxaemia, transplant arteriosclerosis and cancer.
The role of Ang/Tie signaling in lymphangiogenesis.
This review provides an update on current understanding of the angiopoietin/Tie system in lymphangiogenesis and indicates that Ang-2 seems to be involved in the remodeling and stabilization of lymphatic vessels.
The angiopoietin/Tie system plays a key role in remodeling and maturation of blood vessels as well as lymphatic vessels and its precise role in blood and lymphatic development has been a major challenge.
Roles of angiopoietins in kidney development and disease.
Investigations of chimeric wild-type/Tie null mutant embryos show that Tie genes are needed for renal endothelial survival, and imbalanced angiopoietin signaling contributes to glomerular pathobiology.
Angiopoietin: A TIE(d) Balance in Tumor Angiogenesis
A better understanding of the molecular basis of ANG-1 and ANG-2 activity in the pathophysiologic regulation of angiogenesis may set the stage for novel therapy targeting this pathway.
Regulation of Tie2 by angiopoietin-1 and angiopoietin-2 in endothelial cells.
It was discovered that Ang-2 induced all of the same effects on Tie-2 as Ang-1 but at a much reduced level and rate, indicating thatAng-2 likely functions as a partial agonist for Tie- 2 in endothelial cells.
The Angiopoietin ligands and Tie receptors: potential diagnostic biomarkers of vascular disease
Evidence of the change observed in the Angiopoietin/Tie molecules in various pathophysiological conditions is presented and the potential clinical applications of these molecules in vascular complications are discussed.
Regulation of angiopoietin expression by bacterial lipopolysaccharide.
In vivo endotoxemia triggers functional inhibition of the Ang-1/Tie-2 receptor pathway by reducingAng-1 and Tie-2 expression and inducing Ang-2 levels and that this response may contribute to enhanced vascular leakage in sepsis.


Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis.
The discovery of a negative regulator acting on Tie2 emphasizes the need for exquisite regulation of this angiogenic receptor system.
Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization.
In vivo results indicate that angiopoietins may potentiate the effects of other angiogenic cytokines and provide in vivo evidence that Ang1 promotes vascular network maturation, whereas Ang2 works to initiate neovascularization.
Angiopoietin-1 inhibits irradiation- and mannitol-induced apoptosis in endothelial cells.
Ang1 promotes the survival of endothelial cells in irradiation- and mannitol-induced apoptosis through Tie2 receptor binding and PI3-kinase activation, and could be beneficial in maintaining normal endothelial cell integrity during intracoronary irradiation or systemicMannitol therapy.
Angiopoietin-2 at high concentration can enhance endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway
Findings indicate that at high concentrations, Ang2, like Ang1, can be an apoptosis survival factor for endothelial cells through the activation of the Tie2 receptor, PI 3′-kinase and Akt, and thus may be a positive regulator of tumor angiogenesis.
Angiopoietin-1 is inversely related to thymidine phosphorylase expression in human breast cancer, indicating a role in vascular remodeling.
  • M. Currie, S. Gunningham, S. Fox
  • Biology, Medicine
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2001
It is suggested that the Ang/Tie2 pathway plays a significant role in human breast tumor angiogenesis but provide no initial evidence for direct regulation of the pathway by estrogen.
Coadministration of Angiopoietin-1 and Vascular Endothelial Growth Factor Enhances Collateral Vascularization
  • J. Chae, I. Kim, G. Koh
  • Biology, Medicine
    Arteriosclerosis, thrombosis, and vascular biology
  • 2000
In a rabbit ischemic hindlimb model, a combination of Ang1 and VEGF gene delivery produced an enhanced effect on resting and maximal blood flow and capillary formation that was greater than that of either factor alone.
Angiopoietin-1 induces endothelial cell sprouting through the activation of focal adhesion kinase and plasmin secretion.
Angiopoietin-1-induced sprouting activity in endothelial cells may be accomplished by cytoskeletal changes and secretion of proteinases and may be largely mediated through intracellular PI 3'-kinase activation.
Angiopoietins have distinct modular domains essential for receptor binding, dimerization and superclustering
Engineered tetramers of Ang1 are useful in vivo reagents and cause resistance to mustard oil-induced vascular leakage comparable to resistance caused by adenoviral gene delivery.