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Gene Review

Angpt2  -  angiopoietin 2

Rattus norvegicus

Synonyms: ANG-2, Agpt2, Ang-2, Angiopoietin-2
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Disease relevance of Angpt2


High impact information on Angpt2

  • Angiopoietin-2 (Ang2) appears to be a naturally occurring antagonist of the endothelial receptor tyrosine kinase Tie2, an important regulator of vascular stability [6].
  • Destabilization of the endothelium by Ang2 is believed to potentiate the actions of proangiogenic growth factors [6].
  • Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2 [6].
  • By contrast, Ang2 promotes endothelial cell death and vessel regression if the activity of endogenous VEGF is inhibited [7].
  • Angiotensin II induces expression of the Tie2 receptor ligand, angiopoietin-2, in bovine retinal endothelial cells [8].

Chemical compound and disease context of Angpt2


Biological context of Angpt2

  • At the time of peak elevation in Ang-2, Tie2 phosphorylation was found to be markedly increased, consistent with receptor activation [1].
  • In contrast, IGF-I, which did not significantly activate ERK or JNK, stimulated increased Ang2 expression through transcriptional activation [9].
  • These data suggest that Ang2 might modulate both angiogenesis and vascular regression in the rat brain and that capillary regression occurring during deadaptation involves activation of apoptosis [3].
  • Up-regulation of both Ang-2 and VEGF coincided with EC proliferation [10].
  • Ang-1 and Ang-2 promote angiogenesis in this system, stimulating branching morphogenesis and mural cell assembly [11].

Anatomical context of Angpt2

  • Ang-2 has been suggested to be an antagonist of TIE-2, possibly acting to release endothelial cells from the tonic stabilizing influence of Ang-1 [1].
  • In the infarct territory, Ang-2 immunostaining was localized primarily to invading leukocytes at 24 h [1].
  • Ang2 mRNA was increased significantly at 24 h and 48 h after reperfusion, and returned to baseline levels at 72 h, in the jeopardized myocardium [12].
  • This study identifies a mechanism of growth factor-mediated reduction in Ang2 expression in vascular smooth muscle cells (VSMCs) [9].
  • Endothelial Ang-1 and Tie-2 proteins were present in all cerebral vessels of normal brain including those of the choroid plexuses, whereas both these proteins as well as Ang-2 were present in choroid plexus epithelium and in ependymal cells, suggesting that angiopoietins have an autocrine effect on these cell types as well [13].

Associations of Angpt2 with chemical compounds


Regulatory relationships of Angpt2

  • In the 1 h hypoxia group, there was significant induction of Ang-2 expression (31.3% compared to its baseline control) in contrast to relatively mild Ang-1 expression (23.8% compared to its baseline control) [18].

Other interactions of Angpt2

  • At 1 week, Ang-1 expression was partially restored, whereas Ang-2 expression remained elevated [1].
  • In addition, immunohistochemical detection of fibronectin was used to detect BBB breakdown at the lesion site and dual labeling was used to determine whether the vessels demonstrating BBB breakdown expressed endothelial Ang-1 or Ang-2 [13].
  • An apparent relationship between the expression profiles of Flk-1 and Ang-2 was observed [18].
  • These cells responded chemotactically to Ang-1 and Ang-2, and secreted MMP-2 when treated with these factors [11].
  • Treatment of old rats with PDGF-AB with vascular endothelial growth factor and angiopoietin-2 (a combination termed PVA), but not PDGF-AB alone, at the time of IPC decreased TNF-alpha [19].

Analytical, diagnostic and therapeutic context of Angpt2


  1. Reciprocal regulation of angiopoietin-1 and angiopoietin-2 following myocardial infarction in the rat. Sandhu, R., Teichert-Kuliszewska, K., Nag, S., Proteau, G., Robb, M.J., Campbell, A.I., Kuliszewski, M.A., Kutryk, M.J., Stewart, D.J. Cardiovasc. Res. (2004) [Pubmed]
  2. Enhanced expression of angiopoietin-2 and the Tie2 receptor but not angiopoietin-1 or the Tie1 receptor in a rat model of myocardial infarction. Shyu, K.G., Liang, Y.J., Chang, H., Wang, B.W., Leu, J.G., Kuan, P. J. Biomed. Sci. (2004) [Pubmed]
  3. Angiopoietin-2 and rat brain capillary remodeling during adaptation and deadaptation to prolonged mild hypoxia. Pichiule, P., LaManna, J.C. J. Appl. Physiol. (2002) [Pubmed]
  4. Immunohistochemical study of VEGF, angiopoietin 2 and their receptors in the neovascularization following microinjection of C6 glioma cells into rat brain. Péoch, M., Farion, R., Hiou, A., Le Bas, J.F., Pasquier, B., Rémy, C. Anticancer Res. (2002) [Pubmed]
  5. MRI assessment of hemodynamic effects of angiopoietin-2 overexpression in a brain tumor model. Valable, S., Eddi, D., Constans, J.M., Guillamo, J.S., Bernaudin, M., Roussel, S., Petit, E. Neuro-oncology (2009) [Pubmed]
  6. Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2. White, R.R., Shan, S., Rusconi, C.P., Shetty, G., Dewhirst, M.W., Kontos, C.D., Sullenger, B.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  7. Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Lobov, I.B., Brooks, P.C., Lang, R.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  8. Angiotensin II induces expression of the Tie2 receptor ligand, angiopoietin-2, in bovine retinal endothelial cells. Otani, A., Takagi, H., Oh, H., Koyama, S., Honda, Y. Diabetes (2001) [Pubmed]
  9. Transcriptional and posttranscriptional regulation of angiopoietin-2 expression mediated by IGF and PDGF in vascular smooth muscle cells. Phelps, E.D., Updike, D.L., Bullen, E.C., Grammas, P., Howard, E.W. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  10. Expression of angiopoietin-1, angiopoietin-2, and tie receptors after middle cerebral artery occlusion in the rat. Beck, H., Acker, T., Wiessner, C., Allegrini, P.R., Plate, K.H. Am. J. Pathol. (2000) [Pubmed]
  11. Rat aorta-derived mural precursor cells express the Tie2 receptor and respond directly to stimulation by angiopoietins. Iurlaro, M., Scatena, M., Zhu, W.H., Fogel, E., Wieting, S.L., Nicosia, R.F. J. Cell. Sci. (2003) [Pubmed]
  12. Increased expression of angiopoietin-2 and Tie2 receptor in a rat model of myocardial ischaemia/reperfusion. Shyu, K.G., Chang, C.C., Wang, B.W., Kuan, P., Chang, H. Clin. Sci. (2003) [Pubmed]
  13. Altered expression of angiopoietins during blood-brain barrier breakdown and angiogenesis. Nourhaghighi, N., Teichert-Kuliszewska, K., Davis, J., Stewart, D.J., Nag, S. Lab. Invest. (2003) [Pubmed]
  14. Increased renal vascular endothelial growth factor and angiopoietins by angiotensin II infusion is mediated by both AT1 and AT2 receptors. Rizkalla, B., Forbes, J.M., Cooper, M.E., Cao, Z. J. Am. Soc. Nephrol. (2003) [Pubmed]
  15. Angiotensin AT(1) and AT(2) receptors differentially regulate angiopoietin-2 and vascular endothelial growth factor expression and angiogenesis by modulating heparin binding-epidermal growth factor (EGF)-mediated EGF receptor transactivation. Fujiyama, S., Matsubara, H., Nozawa, Y., Maruyama, K., Mori, Y., Tsutsumi, Y., Masaki, H., Uchiyama, Y., Koyama, Y., Nose, A., Iba, O., Tateishi, E., Ogata, N., Jyo, N., Higashiyama, S., Iwasaka, T. Circ. Res. (2001) [Pubmed]
  16. Alterations in expression of angiopoietins and the Tie-2 receptor in the retina of streptozotocin induced diabetic rats. Ohashi, H., Takagi, H., Koyama, S., Oh, H., Watanabe, D., Antonetti, D.A., Matsubara, T., Nagai, K., Arai, H., Kita, T., Honda, Y. Mol. Vis. (2004) [Pubmed]
  17. Angiopoietins are expressed in the normal rat pituitary gland. Nag, S., Nourhaghighi, N., Venugopalan, R., Asa, S.L., Stewart, D.J. Endocr. Pathol. (2005) [Pubmed]
  18. Early effects of hypoxia/reoxygenation on VEGF, ang-1, ang-2 and their receptors in the rat myocardium: implications for myocardial angiogenesis. Ray, P.S., Estrada-Hernandez, T., Sasaki, H., Zhu, L., Maulik, N. Mol. Cell. Biochem. (2000) [Pubmed]
  19. Growth factor-mediated reversal of senescent dysfunction of ischemia-induced cardioprotection. Zheng, J., Chin, A., Duignan, I., Won, K.H., Hong, M.K., Edelberg, J.M. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  20. Morphologic changes of peritoneum and expression of VEGF in encapsulated peritoneal sclerosis rat models. Io, H., Hamada, C., Ro, Y., Ito, Y., Hirahara, I., Tomino, Y. Kidney Int. (2004) [Pubmed]
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