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Gene Review

ANGPT1  -  angiopoietin 1

Homo sapiens

Synonyms: AGP1, AGPT, ANG-1, ANG1, Ang1, ...
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Disease relevance of ANGPT1

  • Depending on the cell type, expression of ANGPT1 and ANGPT2 was either activated or repressed in response to hypoxia or AdCA5 [1].
  • Angiopoietin-1 promotes lymphatic sprouting and hyperplasia [2].
  • Our results reinforce the concept that Ang1 therapy may be useful in settings of tissue edema [2].
  • We examined the RNA content of the gene encoding angiopoietin (Ang)-2, a modifier of angiogenesis, in hepatic metastases of colorectal cancer (CRC) to explore the role of this protein in neovascularization of metastatic foci [3].
  • In conclusion, consistent with the immature phenotype of the cystic epithelium, expression of VEGF, VEGFRs, Ang-1 and Tie-2 is strongly upregulated in cholangiocytes from polycystic liver diseases [4].

High impact information on ANGPT1

  • However, its expression in close proximity with developing blood vessels implicates Angiopoietin-1 in endothelial developmental processes [5].
  • The structure of Angiopoietin-1 differs from that of known angiogenic factors or other ligands for receptor tyrosine kinases [5].
  • Although Angiopoietin-1 binds and induces the tyrosine phosphorylation of TIE2, it does not directly promote the growth of cultured endothelial cells [5].
  • We report the identification of a secreted ligand for TIE2, termed Angiopoietin-1, using a novel expression cloning technique that involves intracellular trapping and detection of the ligand in COS cells [5].
  • Angiopoietin-1 seems to play a crucial role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme [6].

Chemical compound and disease context of ANGPT1


Biological context of ANGPT1


Anatomical context of ANGPT1

  • Expression of mRNA for ANGPT1 in luteal pericytes was not affected by the NO treatment [14].
  • Modulation of Tie2 receptor activity by its angiopoietin ligands is crucial for angiogenesis, blood vessel maturation, and vascular endothelium integrity [15].
  • We found that Ang1 activated lymphatic vessel endothelial proliferation, vessel enlargement, and generation of long endothelial cell filopodia that eventually fused, leading to new sprouts and vessel development [2].
  • In this study we have demonstrated that myeloma cells express several proangiogenic factors, and, in particular, we found that angiopoietin-1 (Ang-1), but not its antagonist Ang-2, was expressed by several human myeloma cell lines (HMCLs) at the mRNA and the protein levels [16].
  • In order to characterize the effects of the angiopoietins on lymphatic vessels, we employed viral vectors for overexpression of Ang1 in adult mouse tissues [2].

Associations of ANGPT1 with chemical compounds

  • We also examined the effect of physiological levels of estrogen on Ang expression [7].
  • Furthermore, angiopoietin-mediated PAF synthesis is partly driven by a relocalization of endogenous VEGF to the cell surface membrane [17].
  • The mechanism of regulation angiopoietin mRNAs level was determined by explant culture in ambient and reduced oxygen, and in the presence of actinomycin D [18].
  • These data suggest a dynamic expression of vascular-specific growth factors in a gonadotrophin-dependent, steroid-independent (VEGF) or steroid-dependent (Ang-1) manner in granulosa cells of peri-ovulatory follicles of primates [19].
  • The increase of flk-1 and flt-1 (VEGF receptors) and tie-2 (Ang1 receptor) induced by ang II was significantly suppressed by PD123319 [20].
  • Ang-1 induced proMMP-3 secretion from synovial cells, which resulted in direct degradation of the cartilaginous matrix [21].

Physical interactions of ANGPT1


Regulatory relationships of ANGPT1


Other interactions of ANGPT1


Analytical, diagnostic and therapeutic context of ANGPT1


  1. Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1. Kelly, B.D., Hackett, S.F., Hirota, K., Oshima, Y., Cai, Z., Berg-Dixon, S., Rowan, A., Yan, Z., Campochiaro, P.A., Semenza, G.L. Circ. Res. (2003) [Pubmed]
  2. Angiopoietin-1 promotes lymphatic sprouting and hyperplasia. Tammela, T., Saaristo, A., Lohela, M., Morisada, T., Tornberg, J., Norrmén, C., Oike, Y., Pajusola, K., Thurston, G., Suda, T., Yla-Herttuala, S., Alitalo, K. Blood (2005) [Pubmed]
  3. Hepatic expression of ANG2 RNA in metastatic colorectal cancer. Ogawa, M., Yamamoto, H., Nagano, H., Miyake, Y., Sugita, Y., Hata, T., Kim, B.N., Ngan, C.Y., Damdinsuren, B., Ikenaga, M., Ikeda, M., Ohue, M., Nakamori, S., Sekimoto, M., Sakon, M., Matsuura, N., Monden, M. Hepatology (2004) [Pubmed]
  4. Effects of angiogenic factor overexpression by human and rodent cholangiocytes in polycystic liver diseases. Fabris, L., Cadamuro, M., Fiorotto, R., Roskams, T., Spirlì, C., Melero, S., Sonzogni, A., Joplin, R.E., Okolicsanyi, L., Strazzabosco, M. Hepatology (2006) [Pubmed]
  5. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Davis, S., Aldrich, T.H., Jones, P.F., Acheson, A., Compton, D.L., Jain, V., Ryan, T.E., Bruno, J., Radziejewski, C., Maisonpierre, P.C., Yancopoulos, G.D. Cell (1996) [Pubmed]
  6. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Suri, C., Jones, P.F., Patan, S., Bartunkova, S., Maisonpierre, P.C., Davis, S., Sato, T.N., Yancopoulos, G.D. Cell (1996) [Pubmed]
  7. Angiopoietin-1 is inversely related to thymidine phosphorylase expression in human breast cancer, indicating a role in vascular remodeling. Currie, M.J., Gunningham, S.P., Han, C., Scott, P.A., Robinson, B.A., Harris, A.L., Fox, S.B. Clin. Cancer Res. (2001) [Pubmed]
  8. Role of angiopoietin-1 in experimental and human pulmonary arterial hypertension. Kugathasan, L., Dutly, A.E., Zhao, Y.D., Deng, Y., Robb, M.J., Keshavjee, S., Stewart, D.J. Chest (2005) [Pubmed]
  9. Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis. Lu, Y.H., Deng, A.G., Li, N., Song, M.N., Yang, X., Liu, J.S. Acta Pharmacol. Sin. (2006) [Pubmed]
  10. Abnormal uterine bleeding during progestin-only contraception may result from free radical-induced alterations in angiopoietin expression. Krikun, G., Critchley, H., Schatz, F., Wan, L., Caze, R., Baergen, R.N., Lockwood, C.J. Am. J. Pathol. (2002) [Pubmed]
  11. Activation of the tie2 receptor by angiopoietin-1 enhances tumor vessel maturation and impairs squamous cell carcinoma growth. Hawighorst, T., Skobe, M., Streit, M., Hong, Y.K., Velasco, P., Brown, L.F., Riccardi, L., Lange-Asschenfeldt, B., Detmar, M. Am. J. Pathol. (2002) [Pubmed]
  12. Cell type-specific expression of angiopoietin-1 and angiopoietin-2 suggests a role in glioblastoma angiogenesis. Stratmann, A., Risau, W., Plate, K.H. Am. J. Pathol. (1998) [Pubmed]
  13. Down-regulation of angiopoietin-1 expression in menorrhagia. Hewett, P., Nijjar, S., Shams, M., Morgan, S., Gupta, J., Ahmed, A. Am. J. Pathol. (2002) [Pubmed]
  14. Isolation and characterization of ovine luteal pericytes and effects of nitric oxide on pericyte expression of angiogenic factors. Beckman, J.D., Grazul-Bilska, A.T., Johnson, M.L., Reynolds, L.P., Redmer, D.A. Endocrine (2006) [Pubmed]
  15. 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]
  16. Proangiogenic properties of human myeloma cells: production of angiopoietin-1 and its potential relationship to myeloma-induced angiogenesis. Giuliani, N., Colla, S., Lazzaretti, M., Sala, R., Roti, G., Mancini, C., Bonomini, S., Lunghi, P., Hojden, M., Genestreti, G., Svaldi, M., Coser, P., Fattori, P.P., Sammarelli, G., Gazzola, G.C., Bataille, R., Almici, C., Caramatti, C., Mangoni, L., Rizzoli, V. Blood (2003) [Pubmed]
  17. Angiopoietins-1 and -2 are both capable of mediating endothelial PAF synthesis: Intracellular signalling pathways. Maliba, R., Lapointe, S., Neagoe, P.E., Brkovic, A., Sirois, M.G. Cell. Signal. (2006) [Pubmed]
  18. The regulation and localization of angiopoietin-1, -2, and their receptor Tie2 in normal and pathologic human placentae. Zhang, E.G., Smith, S.K., Baker, P.N., Charnock-Jones, D.S. Mol. Med. (2001) [Pubmed]
  19. Vascular endothelial growth factor (VEGF) and angiopoietin regulation by gonadotrophin and steroids in macaque granulosa cells during the peri-ovulatory interval. Hazzard, T.M., Molskness, T.A., Chaffin, C.L., Stouffer, R.L. Mol. Hum. Reprod. (1999) [Pubmed]
  20. Regulation of angiogenic factors in angiotensin II infusion model in association with tubulointerstitial injuries. Kitayama, H., Maeshima, Y., Takazawa, Y., Yamamoto, Y., Wu, Y., Ichinose, K., Hirokoshi, K., Sugiyama, H., Yamasaki, Y., Makino, H. Am. J. Hypertens. (2006) [Pubmed]
  21. Angiopoietin 1 directly induces destruction of the rheumatoid joint by cooperative, but independent, signaling via ERK/MAPK and phosphatidylinositol 3-kinase/Akt. Hashiramoto, A., Sakai, C., Yoshida, K., Tsumiyama, K., Miura, Y., Shiozawa, K., Nose, M., Komai, K., Shiozawa, S. Arthritis Rheum. (2007) [Pubmed]
  22. Angiopoietin concentrations in diabetic retinopathy. Patel, J.I., Hykin, P.G., Gregor, Z.J., Boulton, M., Cree, I.A. The British journal of ophthalmology. (2005) [Pubmed]
  23. Comparative integromics on Angiopoietin family members. Katoh, Y., Katoh, M. Int. J. Mol. Med. (2006) [Pubmed]
  24. ESE-1 is a novel transcriptional mediator of angiopoietin-1 expression in the setting of inflammation. Brown, C., Gaspar, J., Pettit, A., Lee, R., Gu, X., Wang, H., Manning, C., Voland, C., Goldring, S.R., Goldring, M.B., Libermann, T.A., Gravallese, E.M., Oettgen, P. J. Biol. Chem. (2004) [Pubmed]
  25. Angiopoietin-1 inhibits endothelial permeability, neutrophil adherence and IL-8 production. Pizurki, L., Zhou, Z., Glynos, K., Roussos, C., Papapetropoulos, A. Br. J. Pharmacol. (2003) [Pubmed]
  26. Effects of protein and gene transfer of the angiopoietin-1 fibrinogen-like receptor-binding domain on endothelial and vessel organization. Weber, C.C., Cai, H., Ehrbar, M., Kubota, H., Martiny-Baron, G., Weber, W., Djonov, V., Weber, E., Mallik, A.S., Fussenegger, M., Frei, K., Hubbell, J.A., Zisch, A.H. J. Biol. Chem. (2005) [Pubmed]
  27. Angiopoietin-1 upregulation by vascular endothelial growth factor in human retinal pigment epithelial cells. Hangai, M., Murata, T., Miyawaki, N., Spee, C., Lim, J.I., He, S., Hinton, D.R., Ryan, S.J. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
  28. Differential regulation of ANG2 and VEGF-A in human granulosa lutein cells by choriogonadotropin. Pietrowski, D., Keck, C. Exp. Clin. Endocrinol. Diabetes (2004) [Pubmed]
  29. Angiopoietin switching regulates angiogenesis and progression of human hepatocellular carcinoma. Sugimachi, K., Tanaka, S., Taguchi, K., Aishima, S., Shimada, M., Tsuneyoshi, M. J. Clin. Pathol. (2003) [Pubmed]
  30. Opposing effect of angiopoietin-1 on VEGF-mediated disruption of endothelial cell-cell interactions requires activation of PKC beta. Wang, Y., Pampou, S., Fujikawa, K., Varticovski, L. J. Cell. Physiol. (2004) [Pubmed]
  31. NERF2, a member of the Ets family of transcription factors, is increased in response to hypoxia and angiopoietin-1: a potential mechanism for Tie2 regulation during hypoxia. Christensen, R.A., Fujikawa, K., Madore, R., Oettgen, P., Varticovski, L. J. Cell. Biochem. (2002) [Pubmed]
  32. Analysis of concerted expression of angiogenic growth factors in acute myeloid leukemia: expression of angiopoietin-2 represents an independent prognostic factor for overall survival. Loges, S., Heil, G., Bruweleit, M., Schoder, V., Butzal, M., Fischer, U., Gehling, U.M., Schuch, G., Hossfeld, D.K., Fiedler, W. J. Clin. Oncol. (2005) [Pubmed]
  33. Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial-specific receptor tyrosine kinase Tie2. Witzenbichler, B., Maisonpierre, P.C., Jones, P., Yancopoulos, G.D., Isner, J.M. J. Biol. Chem. (1998) [Pubmed]
  34. Increased Tie2 expression, enhanced response to angiopoietin-1, and dysregulated angiopoietin-2 expression in hemangioma-derived endothelial cells. Yu, Y., Varughese, J., Brown, L.F., Mulliken, J.B., Bischoff, J. Am. J. Pathol. (2001) [Pubmed]
  35. Hypoxia-inducible factor-1 mediates activation of cultured vascular endothelial cells by inducing multiple angiogenic factors. Yamakawa, M., Liu, L.X., Date, T., Belanger, A.J., Vincent, K.A., Akita, G.Y., Kuriyama, T., Cheng, S.H., Gregory, R.J., Jiang, C. Circ. Res. (2003) [Pubmed]
  36. Expression of angiopoietins, Tie2 and vascular endothelial growth factor in angiogenesis and progression of hepatocellular carcinoma. Zhang, Z.L., Liu, Z.S., Sun, Q. World J. Gastroenterol. (2006) [Pubmed]
  37. Human podocytes express angiopoietin 1, a potential regulator of glomerular vascular endothelial growth factor. Satchell, S.C., Harper, S.J., Tooke, J.E., Kerjaschki, D., Saleem, M.A., Mathieson, P.W. J. Am. Soc. Nephrol. (2002) [Pubmed]
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