Angiopoietin 1 Explained

Angiopoietin 1 is a type of angiopoietin and is encoded by the gene ANGPT1.

Angiopoietins are proteins with important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The protein encoded by this gene is a secreted glycoprotein that activates the receptor by inducing its tyrosine phosphorylation. It plays a critical role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme. The protein also contributes to blood vessel maturation and stability, and may be involved in early development of the heart.^[1] During pregnancy, angiopoietins act complementary to the VEGF system and contribute to endothelial cell survival and the remodeling of vessels. Few studies have examined the role of angiopoietins in human pregnancy complications like preeclampsia and intrauterine growth restriction (IUGR).

A knockout model of ANGPT1 was introduced in mice embryos. Results showed that embryos began to appear abnormal by day 11 and were dead by day 12.5 of pregnancy. The embryos showed prominent defects in endocardial and myocardial development as well as a less complex vascular network.

^{[2] [3]}

Interactions

Angiopoietin 1 has been shown to interact with TEK tyrosine kinase.^{[4] [5] [6] [7]}

Placental Malaria

Recently, studies in malaria-endemic areas suggest that placental malaria (PM) may be associated with a dysregulation in angiopoietins. Increased levels of angiopoietin-1 appear to be associated with a decrease in placental weight and placental barrier thickness in women infected with Plasmodium (the causative agent of malaria).^[8] In a mouse model of PM, Plasmodium infection of pregnant mice led to decreased angiopoietin-1, increased angiopoietin-2, and an elevated ratio of angiopoietin-2/angiopoietin-1 in the placenta.^[9] This suggests that angiopoietin levels could be clinically significant biomarkers to identify mothers infected with PM.

See also

• Angiopoietin

Further reading

• Nakajima D, Okazaki N, Yamakawa H . Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones . DNA Res. . 9 . 3 . 99–106 . 2003 . 12168954 . 10.1093/dnares/9.3.99 . free .
• Metheny-Barlow LJ, Li LY . The enigmatic role of angiopoietin-1 in tumor angiogenesis . Cell Res. . 13 . 5 . 309–17 . 2004 . 14672554 . 10.1038/sj.cr.7290176 . free .
• Makinde T, Murphy RF, Agrawal DK . Immunomodulatory role of vascular endothelial growth factor and angiopoietin-1 in airway remodeling . Curr. Mol. Med. . 6 . 8 . 831–41 . 2007 . 17168735 . 10.2174/156652406779010795 .
• Nomura N, Miyajima N, Sazuka T . Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1 . DNA Res. . 1 . 1 . 27–35 . 1995 . 7584026 . 10.1093/dnares/1.1.27 . free .
• Nomura N, Miyajima N, Sazuka T . Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1 (supplement) . DNA Res. . 1 . 1 . 47–56 . 1995 . 7584028 . 10.1093/dnares/1.1.47 . free .
• Rüegg C, Pytela R . Sequence of a human transcript expressed in T-lymphocytes and encoding a fibrinogen-like protein . Gene . 160 . 2 . 257–62 . 1995 . 7642106 . 10.1016/0378-1119(95)00240-7 .
• Davis S, Aldrich TH, Jones PF . Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning . Cell . 87 . 7 . 1161–9 . 1997 . 8980223 . 10.1016/S0092-8674(00)81812-7 . 17197564 . free .
• Suri C, Jones PF, Patan S . Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis . Cell . 87 . 7 . 1171–80 . 1997 . 8980224 . 10.1016/S0092-8674(00)81813-9 . 15926708 . free .
• Maisonpierre PC, Suri C, Jones PF . Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis . Science . 277 . 5322 . 55–60 . 1997 . 9204896 . 10.1126/science.277.5322.55 .
• Ristimäki A, Narko K, Enholm B . Proinflammatory cytokines regulate expression of the lymphatic endothelial mitogen vascular endothelial growth factor-C . J. Biol. Chem. . 273 . 14 . 8413–8 . 1998 . 9525952 . 10.1074/jbc.273.14.8413 . free .
• Cheung AH, Stewart RJ, Marsden PA . Endothelial Tie2/Tek ligands angiopoietin-1 (ANGPT1) and angiopoietin-2 (ANGPT2): regional localization of the human genes to 8q22.3-q23 and 8p23 . Genomics . 48 . 3 . 389–91 . 1998 . 9545648 . 10.1006/geno.1997.5207 .
• Witzenbichler B, Maisonpierre PC, Jones P . Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial-specific receptor tyrosine kinase Tie2 . J. Biol. Chem. . 273 . 29 . 18514–21 . 1998 . 9660821 . 10.1074/jbc.273.29.18514 . free .
• Sato A, Iwama A, Takakura N . Characterization of TEK receptor tyrosine kinase and its ligands, Angiopoietins, in human hematopoietic progenitor cells . Int. Immunol. . 10 . 8 . 1217–27 . 1998 . 9723709 . 10.1093/intimm/10.8.1217 . free .
• Valenzuela DM, Griffiths JA, Rojas J . Angiopoietins 3 and 4: diverging gene counterparts in mice and humans . Proc. Natl. Acad. Sci. U.S.A. . 96 . 5 . 1904–9 . 1999 . 10051567 . 10.1073/pnas.96.5.1904 . 26709 . 1999PNAS...96.1904V . free .
• Grosios K, Leek JP, Markham AF . Assignment of ANGPT4, ANGPT1, and ANGPT2 encoding angiopoietins 4, 1 and 2 to human chromosome bands 20p13, 8q22.3→q23 and 8p23.1, respectively, by in situ hybridization and radiation hybrid mapping . Cytogenet. Cell Genet. . 84 . 1–2 . 118–20 . 1999 . 10343124 . 10.1159/000015235 . 40232421 .
• Procopio WN, Pelavin PI, Lee WM, Yielding NM . Angiopoietin-1 and -2 coiled coil domains mediate distinct homo-oligomerization patterns, but fibrinogen-like domains mediate ligand activity . J. Biol. Chem. . 274 . 42 . 30196–201 . 1999 . 10514510 . 10.1074/jbc.274.42.30196 . free .
• Huang YQ, Li JJ, Karpatkin S . Identification of a family of alternatively spliced mRNA species of angiopoietin-1 . Blood . 95 . 6 . 1993–9 . 2000 . 10706866 . 10.1182/blood.V95.6.1993. 34946654 .
• Kim I, Kim JH, Ryu YS . Characterization and expression of a novel alternatively spliced human angiopoietin-2 . J. Biol. Chem. . 275 . 24 . 18550–6 . 2000 . 10766762 . 10.1074/jbc.M910084199 . free .
• Dunk C, Shams M, Nijjar S . Angiopoietin-1 and angiopoietin-2 activate trophoblast Tie-2 to promote growth and migration during placental development . Am. J. Pathol. . 156 . 6 . 2185–99 . 2000 . 10854239 . 10.1016/S0002-9440(10)65089-4. 1850068 .
• Krikun G, Schatz F, Finlay T . Expression of angiopoietin-2 by human endometrial endothelial cells: regulation by hypoxia and inflammation . Biochem. Biophys. Res. Commun. . 275 . 1 . 159–63 . 2000 . 10944458 . 10.1006/bbrc.2000.3277 . free .

Notes and References

1. Web site: Entrez Gene: ANGPT1 angiopoietin 1.
2. 10.1016/S0092-8674(00)81813-9. 8980224. Requisite Role of Angiopoietin-1, a Ligand for the TIE2 Receptor, during Embryonic Angiogenesis. Cell. 87. 7. 1171–80. 1996. Suri. Chitra. Jones. Pamela F. Patan. Sybill. Bartunkova. Sona. Maisonpierre. Peter C. Davis. Samuel. Sato. Thomas N. Yancopoulos. George D. 15926708. free.
3. Kappou D, Sifakis S, Konstantinidou A, et al. Role of angiopoietin/Tie system in pregnancy.Experimental and Therapeutic Medicine. 2015; 9(4): 1091-1096.
4. Fiedler . Ulrike . Krissl . Tanja . Koidl . Stefanie . Weiss . Cornelia . Koblizek . Thomas . Deutsch . Urban . Martiny-Baron . Georg . Marmé . Dieter . Augustin . Hellmut G . Jan 2003 . Angiopoietin-1 and angiopoietin-2 share the same binding domains in the Tie-2 receptor involving the first Ig-like loop and the epidermal growth factor-like repeats . J. Biol. Chem. . 278 . 3 . 1721–7 . United States. 0021-9258. 12427764 . 10.1074/jbc.M208550200 . free .
5. 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 . Dec 1996 . Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning . Cell . 87 . 7 . 1161–9 . United States. 0092-8674. 8980223 . 10.1016/S0092-8674(00)81812-7 . 17197564 . free .
6. Sato . A . Iwama A . Takakura N . Nishio H . Yancopoulos G D . Suda T . Aug 1998 . Characterization of TEK receptor tyrosine kinase and its ligands, Angiopoietins, in human hematopoietic progenitor cells . Int. Immunol. . 10 . 8 . 1217–27 . ENGLAND. 0953-8178. 9723709 . 10.1093/intimm/10.8.1217 . free .
7. Maisonpierre . P C . Suri . C . Jones . P F . Bartunkova . S . Wiegand . S J . Radziejewski . C . Compton . D . McClain . J . Aldrich . T H . Papadopoulos . N . Daly . T J . Davis . S . Sato . T N . Yancopoulos . G D . Jul 1997 . Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis . . 277 . 5322 . 55–60 . UNITED STATES. 0036-8075. 9204896 . 10.1126/science.277.5322.55 .
8. Ataíde. Ricardo. Murillo. Oscar. Dombrowski. Jamille G.. Souza. Rodrigo M.. Lima. Flávia A.. Lima. Giselle F. M. C.. Hristov. Angélica D.. Valle. Suiane C. N.. Santi. Silvia M. Di. 2015-06-19. Malaria in Pregnancy Interacts with and Alters the Angiogenic Profiles of the Placenta. PLOS Neglected Tropical Diseases. 9. 6. e0003824. 10.1371/journal.pntd.0003824. 1935-2735. 4475015. 26090803 . free .
9. Silver. Karlee L.. Zhong. Kathleen. Leke. Rose G. F.. Taylor. Diane Wallace. Kain. Kevin C.. 2010-03-01. Dysregulation of angiopoietins is associated with placental malaria and low birth weight. PLOS ONE. 5. 3. e9481. 10.1371/journal.pone.0009481. 1932-6203. 2830425. 20208992. 2010PLoSO...5.9481S. free.