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Gene Review

Ang  -  angiogenin, ribonuclease, RNase A family, 5

Mus musculus

Synonyms: AI385586, Ang1, Angiogenin, Angiogenin-1, RNase 5, ...
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Disease relevance of Ang1

  • However, when Ang1 expression was initiated simultaneously with that of VEGF, it strongly suppressed VEGF-induced NV and prevented retinal detachment [1].
  • The contribution of COMP-Ang1 in renal interstitial fibrosis, however, remains to be clarified [2].
  • This study investigated the effects of COMP-Ang1 on peritubular capillary EC in the renal cortex and the renal fibrogenic process that is triggered by unilateral ureteral obstruction [2].
  • These observations demonstrate the potential of Ang1 as a new therapeutic modality for MC dropout in diseases such as diabetic retinopathies [3].
  • Increased expression of Ang1 in eyes with severe retinal ischemia or in eyes with rupture of Bruch's membrane significantly suppressed the development of retinal or choroidal neovascularization, respectively [4].

High impact information on Ang1

  • The angiopoietins Ang-1 and Ang-2 have been identified as ligands of the receptor tyrosine kinase Tie-2 (refs. 1,2) [5].
  • Direct comparison of transgenic mice overexpressing these factors in the skin revealed that the VEGF-induced blood vessels were leaky, whereas those induced by Ang1 were nonleaky [6].
  • Finally, ephrinB ligands induce capillary sprouting in vitro with a similar efficiency as angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF), demonstrating a stimulatory role of ephrins in the remodeling of the developing vascular system [7].
  • In Langendorff-perfused guinea pig hearts, mast cell degranulation with compound 48/80 released Ang I-forming activity [8].
  • Taken together, these findings indicate that COMP-Ang1 can promote wound healing in diabetes through enhanced angiogenesis, lymphangiogenesis, and blood flow [9].

Chemical compound and disease context of Ang1

  • Because endotoxin-induced shock is a condition with microvascular leakage resulting from inflammation, we examined the potential therapeutic benefit of Ang1 in a murine model of lipopolysaccharide (LPS)-induced endotoxic shock [10].
  • Our group has shown previously that RV inhibits angiotensin II (Ang II)-induced Akt activation and, consequently, vascular smooth muscle cell (VSMC) hypertrophy [11].
  • The highly lipophilic ACE inhibitor imidapril (Vitortrade mark) (30 mg kg(-1)) attenuated the development of weight loss in mice bearing the MAC16 tumour, suggesting that Ang II may play a role in the development of cachexia in this model [12].
  • Recombinant human Ang-1 antisense eukaryotic expression vector was constructed by directional cloning, and transfected by lipofectin method into human gastric cancer line SGC7901 with high Ang-1 expression level [13].

Biological context of Ang1


Anatomical context of Ang1


Associations of Ang1 with chemical compounds

  • This study investigated the expression patterns of the Ang-Tie-2 family of endothelium-specific receptor tyrosine kinases and vascular endothelial growth factors and their receptors (VEGF-VEGFR system) during postnatal mouse lung development [21].
  • The Ang1-induced ROS was identified as hydrogen peroxide (H2O2) using adenovirus-catalase infection [22].
  • We found that human umbilical vein endothelial cells treated with Ang1 produce ROS transiently, which was suppressed by NADPH oxidase inhibitor, diphenylene-iodonium chloride, and rotenone [22].
  • After intraperitoneal glucose challenge, COMP-Ang1 significantly lowered plasma glucose levels [23].
  • Examination of the uteri revealed Ang-2 mRNA and protein expression in the oestrogen-dominated cycling phase and the progesterone-dominated mated phase, whereas Ang-1 expression was restricted to the mated phase [24].

Other interactions of Ang1

  • In the present study, the relationship of Angrp to Ang has been investigated by producing both proteins in bacteria and comparing their functional properties [25].
  • This and other evidence suggests that the RNase A superfamily originated from an RNase 5-like gene and expanded in mammals [26].
  • A chimeric mouse/human antibody directed against the human transferrin receptor (E6) was fused at its CH2 domain to the gene for a human angiogenic ribonuclease, angiogenin (Ang) [27].
  • The enhanced survival rate induced by Ang1 was accompanied by an improvement in hemodynamic function, reduced lung injury, a lower expression of inflammatory adhesion molecules, and preserved eNOS activity in the lung tissue [10].

Analytical, diagnostic and therapeutic context of Ang1

  • Although the Ang gene was not isolated from this library, it was possible to amplify this gene from 129 mouse genomic DNA by the polymerase chain reaction (PCR) [16].
  • Sequence analysis showed that the 129 strain Ang gene is identical to the BALB/c gene throughout the coding region [16].
  • Using semiquantitative RT-PCR, we demonstrate that DEX treatment down regulates Ang-1 mRNA levels by 3- to 4-fold [20].
  • We previously reported that overexpression of Ang1 in MCF7 xenograft tumors facilitated vessel stabilization by mural cells, and that cultured SMC express Tie2 [28].
  • Intravenous injection of adenovirus encoding VEGF (Adeno-VEGF) resulted in widespread tissue oedema within 1-2 days after administration, whereas injection of Adeno-Ang1 resulted in the skin vessels becoming less leaky in response to topical inflammatory stimuli or local injection of VEGF [29].


  1. Angiopoietin 1 prevents retinal detachment in an aggressive model of proliferative retinopathy, but has no effect on established neovascularization. Nambu, H., Umeda, N., Kachi, S., Oshima, Y., Akiyama, H., Nambu, R., Campochiaro, P.A. J. Cell. Physiol. (2005) [Pubmed]
  2. COMP-angiopoietin-1 ameliorates renal fibrosis in a unilateral ureteral obstruction model. Kim, W., Moon, S.O., Lee, S.Y., Jang, K.Y., Cho, C.H., Koh, G.Y., Choi, K.S., Yoon, K.H., Sung, M.J., Kim, D.H., Lee, S., Kang, K.P., Park, S.K. J. Am. Soc. Nephrol. (2006) [Pubmed]
  3. Recombinant angiopoietin-1 restores higher-order architecture of growing blood vessels in mice in the absence of mural cells. Uemura, A., Ogawa, M., Hirashima, M., Fujiwara, T., Koyama, S., Takagi, H., Honda, Y., Wiegand, S.J., Yancopoulos, G.D., Nishikawa, S. J. Clin. Invest. (2002) [Pubmed]
  4. Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood-retinal barrier. Nambu, H., Nambu, R., Oshima, Y., Hackett, S.F., Okoye, G., Wiegand, S., Yancopoulos, G., Zack, D.J., Campochiaro, P.A. Gene Ther. (2004) [Pubmed]
  5. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Fiedler, U., Reiss, Y., Scharpfenecker, M., Grunow, V., Koidl, S., Thurston, G., Gale, N.W., Witzenrath, M., Rosseau, S., Suttorp, N., Sobke, A., Herrmann, M., Preissner, K.T., Vajkoczy, P., Augustin, H.G. Nat. Med. (2006) [Pubmed]
  6. Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Thurston, G., Suri, C., Smith, K., McClain, J., Sato, T.N., Yancopoulos, G.D., McDonald, D.M. Science (1999) [Pubmed]
  7. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Adams, R.H., Wilkinson, G.A., Weiss, C., Diella, F., Gale, N.W., Deutsch, U., Risau, W., Klein, R. Genes Dev. (1999) [Pubmed]
  8. Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion. Mackins, C.J., Kano, S., Seyedi, N., Schäfer, U., Reid, A.C., Machida, T., Silver, R.B., Levi, R. J. Clin. Invest. (2006) [Pubmed]
  9. COMP-angiopoietin-1 promotes wound healing through enhanced angiogenesis, lymphangiogenesis, and blood flow in a diabetic mouse model. Cho, C.H., Sung, H.K., Kim, K.T., Cheon, H.G., Oh, G.T., Hong, H.J., Yoo, O.J., Koh, G.Y. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  10. Protective role of angiopoietin-1 in endotoxic shock. Witzenbichler, B., Westermann, D., Knueppel, S., Schultheiss, H.P., Tschope, C. Circulation (2005) [Pubmed]
  11. Resveratrol inhibits angiotensin II- and epidermal growth factor-mediated Akt activation: role of Gab1 and Shp2. Haider, U.G., Roos, T.U., Kontaridis, M.I., Neel, B.G., Sorescu, D., Griendling, K.K., Vollmar, A.M., Dirsch, V.M. Mol. Pharmacol. (2005) [Pubmed]
  12. Angiotensin II directly induces muscle protein catabolism through the ubiquitin-proteasome proteolytic pathway and may play a role in cancer cachexia. Sanders, P.M., Russell, S.T., Tisdale, M.J. Br. J. Cancer (2005) [Pubmed]
  13. Antisense angiopoietin-1 inhibits tumorigenesis and angiogenesis of gastric cancer. Wang, J., Wu, K.C., Zhang, D.X., Fan, D.M. World J. Gastroenterol. (2006) [Pubmed]
  14. Hepatocyte growth factor mediates angiopoietin-induced smooth muscle cell recruitment. Kobayashi, H., DeBusk, L.M., Babichev, Y.O., Dumont, D.J., Lin, P.C. Blood (2006) [Pubmed]
  15. Angiopoietin 2 stimulates migration and tube-like structure formation of murine brain capillary endothelial cells through c-Fes and c-Fyn. Mochizuki, Y., Nakamura, T., Kanetake, H., Kanda, S. J. Cell. Sci. (2002) [Pubmed]
  16. The mouse angiogenin gene family: structures of an angiogenin-related protein gene and two pseudogenes. Brown, W.E., Nobile, V., Subramanian, V., Shapiro, R. Genomics (1995) [Pubmed]
  17. The mouse RNase 4 and RNase 5/ang 1 locus utilizes dual promoters for tissue-specific expression. Dyer, K.D., Rosenberg, H.F. Nucleic Acids Res. (2005) [Pubmed]
  18. Expression and regulation of murine macrophage angiopoietin-2. Hubbard, N.E., Lim, D., Mukutmoni, M., Cai, A., Erickson, K.L. Cell. Immunol. (2005) [Pubmed]
  19. Abnormal recruitment of periendothelial cells to lymphatic capillaries in digestive organs of angiopoietin-2-deficient mice. Shimoda, H., Bernas, M.J., Witte, M.H., Gale, N.W., Yancopoulos, G.D., Kato, S. Cell Tissue Res. (2007) [Pubmed]
  20. Expressional regulation of the angiopoietin-1 and -2 and the endothelial-specific receptor tyrosine kinase Tie2 in adrenal atrophy: a study of adrenocorticotropin-induced repair. Féraud, O., Mallet, C., Vilgrain, I. Endocrinology (2003) [Pubmed]
  21. Expression of angiogenic factors and their receptors in postnatal mouse developing lung. Tsao, P.N., Li, H., Wei, S.C., Ko, M.L., Chou, H.C., Hsieh, W.S., Hsieh, F.J. J. Formos. Med. Assoc. (2004) [Pubmed]
  22. Hydrogen peroxide produced by angiopoietin-1 mediates angiogenesis. Kim, Y.M., Kim, K.E., Koh, G.Y., Ho, Y.S., Lee, K.J. Cancer Res. (2006) [Pubmed]
  23. Renoprotective effect of COMP-angiopoietin-1 in db/db mice with type 2 diabetes. Lee, S., Kim, W., Moon, S.O., Sung, M.J., Kim, D.H., Kang, K.P., Jang, K.Y., Lee, S.Y., Park, B.H., Koh, G.Y., Park, S.K. Nephrol. Dial. Transplant. (2007) [Pubmed]
  24. Angiopoietin-1 and -2 mRNA and protein expression in mouse preimplantation embryos and uteri suggests a role in angiogenesis during implantation. Hess, A.P., Hirchenhain, J., Schanz, A., Talbi, S., Hamilton, A.E., Giudice, L.C., Krüssel, J.S. Reprod. Fertil. Dev. (2006) [Pubmed]
  25. Characterization of mouse angiogenin-related protein: implications for functional studies on angiogenin. Nobile, V., Vallee, B.L., Shapiro, R. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  26. The ribonuclease A superfamily of mammals and birds: identifying new members and tracing evolutionary histories. Cho, S., Beintema, J.J., Zhang, J. Genomics (2005) [Pubmed]
  27. Antitransferrin receptor antibody-RNase fusion protein expressed in the mammary gland of transgenic mice. Newton, D.L., Pollock, D., DiTullio, P., Echelard, Y., Harvey, M., Wilburn, B., Williams, J., Hoogenboom, H.R., Raus, J.C., Meade, H.M., Rybak, S.M. J. Immunol. Methods (1999) [Pubmed]
  28. Direct chemotactic action of angiopoietin-1 on mesenchymal cells in the presence of VEGF. Metheny-Barlow, L.J., Tian, S., Hayes, A.J., Li, L.Y. Microvasc. Res. (2004) [Pubmed]
  29. Complementary actions of VEGF and angiopoietin-1 on blood vessel growth and leakage. Thurston, G. J. Anat. (2002) [Pubmed]
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