Role of the angiopoietin/Tie system in pregnancy (Review)

Kappou,D.; Sifakis,S.; Konstantinidou,A.; Papantoniou,N.; Spandidos,D. A.

doi:10.3892/etm.2015.2280

Role of the angiopoietin/Tie system in pregnancy (Review)

Authors:
- D. Kappou
- S. Sifakis
- A. Konstantinidou
- N. Papantoniou
- D. A. Spandidos
View Affiliations

Affiliations: First Department of Obstetrics and Gynecology, University of Athens, Athens, Greece, Department of Obstetrics and Gynecology, University of Crete Medical School, Heraklion, Crete, Greece, First Department of Pathology, University of Athens Medical School, Athens, Greece, Third Department of Obstetrics and Gynecology, University of Athens, Athens, Greece, Laboratory of Clinical Virology, University of Crete Medical School, Heraklion, Crete, Greece
Published online on: February 9, 2015 https://doi.org/10.3892/etm.2015.2280
Pages: 1091-1096
Copyright: © Kappou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Angiopoietin‑1 and ‑2 are endogenous ligands for the vascular endothelium-specific receptor tyrosine kinase Tie‑2. The angiopoietin/Tie system plays a critical role in the regulation of endothelial cell survival and vascular maturation and stability. Apart from its well‑established role in vascular morphogenesis, emerging data support the involvement of angiopoietins in inflammation and various malignancies. Previous studies have underlined the significance of several angiogenic factors in normal placental development. In addition, angiogenic imbalance is observed in pregnancy complications related to impaired placentation, such as preeclampsia (PE) and intrauterine growth restriction (IUGR). However, there is only limited information available on the role of the angiopoietin/Tie system in the establishment of a competent feto‑maternal vascular system. In this review, we present the current knowledge regarding the role of angiopoietins in normal pregnancy and pregnancy complications.

View Figures

View References

1	Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ and Holash J: Vascular-specific growth factors and blood vessel formation. Nature. 407:242–248. 2000. View Article : Google Scholar : PubMed/NCBI
2	Maynard SE and Karumanchi SA: Angiogenic factors and preeclampsia. Semin Nephrol. 31:33–46. 2011. View Article : Google Scholar : PubMed/NCBI
3	Gourvas V, Dalpa E, Konstantinidou A, Vrachnis N, Spandidos DA and Sifakis S: Angiogenic factors in placentas from pregnancies complicated by fetal growth restriction (review). Mol Med Rep. 6:23–27. 2012.PubMed/NCBI
4	Chaiworapongsa T, Romero R, Korzeniewski SJ, et al: Maternal plasma concentrations of angiogenic/antiangiogenic factors in the third trimester of pregnancy to identify the patient at risk for stillbirth at or near term and severe late preeclampsia. Am J Obstet Gynecol. 208:287.e1–287.e15. 2013. View Article : Google Scholar
5	Gómez-Arriaga PI, Herraiz I, López-Jiménez EA, Escribano D, Denk B and Galindo A: Uterine artery Doppler and sFlt-1/PlGF ratio: Prognostic value in early-onset pre-eclampsia. Ultrasound Obstet Gynecol. 43:525–532. 2014. View Article : Google Scholar
6	Andraweera PH, Dekker GA and Roberts CT: The vascular endothelial growth factor family in adverse pregnancy outcomes. Hum Reprod Update. 18:436–457. 2012. View Article : Google Scholar : PubMed/NCBI
7	Charnock-Jones DS: Soluble flt-1 and the angiopoietins in the development and regulation of placental vasculature. J Anat. 200:607–615. 2002. View Article : Google Scholar : PubMed/NCBI
8	Park SW, Yun JH and Kim JH, Kim KW, Cho CH and Kim JH: Angiopoietin 2 induces pericyte apoptosis via α3β1 integrin signaling in diabetic retinopathy. Diabetes. 63:3057–3068. 2014. View Article : Google Scholar : PubMed/NCBI
9	Saharinen P, Eklund L, Pulkki K, Bono P and Alitalo K: VEGF and angiopoietin signaling in tumor angiogenesis and metastasis. Trends Mol Med. 17:347–362. 2011. View Article : Google Scholar : PubMed/NCBI
10	Mussap M, Cibecchini F, Noto A and Fanos V: In search of biomarkers for diagnosing and managing neonatal sepsis: The role of angiopoietins. J Matern Fetal Neonatal Med. 26(Suppl 2): 24–26. 2013. View Article : Google Scholar : PubMed/NCBI
11	Thurston G: Role of Angiopoietins and Tie receptor tyrosine kinases in angiogenesis and lymphangiogenesis. Cell Tissue Res. 314:61–68. 2003. View Article : Google Scholar : PubMed/NCBI
12	Thomas M and Augustin HG: The role of the Angiopoietins in vascular morphogenesis. Angiogenesis. 12:125–137. 2009. View Article : Google Scholar : PubMed/NCBI
13	Maisonpierre PC, Suri C, Jones PF, et al: Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 277:55–60. 1997. View Article : Google Scholar : PubMed/NCBI
14	Davis S, Aldrich TH, Jones PF, et al: Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell. 87:1161–1169. 1996. View Article : Google Scholar : PubMed/NCBI
15	Khan AA, Sandhya VK, Singh P, et al: Signalling network map of endothelial TEK tyrosine kinase. J Signal Transduct. 2014:1730262014. View Article : Google Scholar
16	Daly C, Wong V, Burova E, et al: Angiopoietin-1 modulates endothelial cell function and gene expression via the transcription factor FKHR (FOXO1). Genes Dev. 18:1060–1071. 2004. View Article : Google Scholar : PubMed/NCBI
17	Coffelt SB, Tal AO, Scholz A, et al: Angiopoietin-2 regulates gene expression in TIE2-expressing monocytes and augments their inherent proangiogenic functions. Cancer Res. 70:5270–5280. 2010. View Article : Google Scholar : PubMed/NCBI
18	Yuan HT, Venkatesha S, Chan B, Deutsch U, Mammoto T, Sukhatme VP, Woolf AS and Karumanchi SA: Activation of the orphan endothelial receptor Tie1 modifies Tie2-mediated intracellular signaling and cell survival. FASEB J. 21:3171–3183. 2007. View Article : Google Scholar : PubMed/NCBI
19	Augustin HG, Koh GY, Thurston G and Alitalo K: Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol. 10:165–177. 2009. View Article : Google Scholar : PubMed/NCBI
20	Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, Glazer N, Holash J, McDonald DM and Yancopoulos GD: Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med. 6:460–463. 2000. View Article : Google Scholar : PubMed/NCBI
21	Scharpfenecker M, Fiedler U, Reiss Y and Augustin HG: The Tie-2 ligand angiopoietin-2 destabilizes quiescent endothelium through an internal autocrine loop mechanism. J Cell Sci. 118:771–780. 2005. View Article : Google Scholar : PubMed/NCBI
22	Daly C, Eichten A, Castanaro C, et al: Angiopoietin-2 functions as a Tie2 agonist in tumor models, where it limits the effects of VEGF inhibition. Cancer Res. 73:108–118. 2013. View Article : Google Scholar
23	Teichert-Kuliszewska K, Maisonpierre PC, Jones N, Campbell AI, Master Z, Bendeck MP, Alitalo K, Dumont DJ, Yancopoulos GD and Stewart DJ: Biological action of angiopoietin-2 in a fibrin matrix model of angiogenesis is associated with activation of Tie2. Cardiovasc Res. 49:659–670. 2001. View Article : Google Scholar : PubMed/NCBI
24	Gale NW, Thurston G, Hackett SF, Renard R, Wang Q, McClain J, Martin C, Witte C, Witte MH and Jackson D: Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1. Dev Cell. 3:411–423. 2002. View Article : Google Scholar : PubMed/NCBI
25	Felcht M, Luck R, Schering A, et al: Angiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling. J Clin Invest. 122:1991–2005. 2012. View Article : Google Scholar : PubMed/NCBI
26	Fiedler U, Reiss Y, Scharpfenecker M, et al: Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med. 12:235–239. 2006. View Article : Google Scholar : PubMed/NCBI
27	Dunk C, Shams M, Nijjar S, Rhaman M, Qiu Y, Bussolati B and Ahmed A: Angiopoietin-1 and angiopoietin-2 activate trophoblast Tie-2 to promote growth and migration during placental development. Am J Pathol. 156:2185–2199. 2000. View Article : Google Scholar : PubMed/NCBI
28	Shim WS, Ho IA and Wong PE: Angiopoietin: A TIE(d) balance in tumor angiogenesis. Mol Cancer Res. 5:655–665. 2007. View Article : Google Scholar : PubMed/NCBI
29	Brunckhorst MK, Xu Y, Lu R and Yu Q: Angiopoietins promote ovarian cancer progression by establishing a procancer microenvironment. Am J Pathol. 184:2285–2296. 2014. View Article : Google Scholar : PubMed/NCBI
30	Huang H, Bhat A, Woodnutt G and Lappe R: Targeting the ANGPT-TIE2 pathway in malignancy. Nat Rev Cancer. 10:575–585. 2010. View Article : Google Scholar : PubMed/NCBI
31	Biel NM and Siemann DW: Targeting the Angiopoietin-2/Tie-2 axis in conjunction with VEGF signal interference. Cancer Lett. Oct 12–2014.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
32	Mazzieri R, Pucci F, Moi D, et al: Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell. 19:512–526. 2011. View Article : Google Scholar : PubMed/NCBI
33	Goede V, Coutelle O, Neuneier J, et al: Identification of serum angiopoietin-2 as a biomarker for clinical outcome of colorectal cancer patients treated with bevacizumab-containing therapy. Br J Cancer. 103:1407–1414. 2010. View Article : Google Scholar : PubMed/NCBI
34	Helfrich I, Edler L, Sucker A, et al: Angiopoietin-2 levels are associated with disease progression in metastatic malignant melanoma. Clin Cancer Res. 15:1384–1392. 2009. View Article : Google Scholar : PubMed/NCBI
35	Geva E, Ginzinger DG, Zaloudek CJ, Moore DH, Byrne A and Jaffe RB: Human placental vascular development: Vasculogenic and angiogenic (branching and nonbranching) transformation is regulated by vascular endothelial growth factor-A, angiopoietin-1, and angiopoietin-2. J Clin Endocrinol Metab. 87:4213–4224. 2002. View Article : Google Scholar : PubMed/NCBI
36	Zhang EG, Smith SK, Baker PN and Charnock-Jones DS: The regulation and localization of angiopoietin-1, -2, and their receptor Tie2 in normal and pathologic human placentae. Mol Med. 7:624–635. 2001.
37	Leinonen E, Wathén KA, Alfthan H, Ylikorkala O, Andersson S, Stenman UH and Vuorela P: Maternal serum angiopoietin-1 and -2 and tie-2 in early pregnancy ending in preeclampsia or intrauterine growth retardation. J Clin Endocrinol Metab. 95:126–133. 2010. View Article : Google Scholar
38	Hirokoshi K, Maeshima Y, Kobayashi K, Matsuura E, Sugiyama H, Yamasaki Y, Masuyama H, Hiramatsu Y and Makino H: Elevated serum sFlt-1/Ang-2 ratio in women with preeclampsia. Nephron Clin Pract. 106:c43–c50. 2007. View Article : Google Scholar : PubMed/NCBI
39	Seval Y, Sati L, Celik-Ozenci C, Taskin O and Demir R: The distribution of angiopoietin-1, angiopoietin-2 and their receptors tie-1 and tie-2 in the very early human placenta. Placenta. 29:809–815. 2008. View Article : Google Scholar : PubMed/NCBI
40	Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN and Yancopoulos GD: Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 87:1171–1180. 1996. View Article : Google Scholar : PubMed/NCBI
41	Geva E, Ginzinger DG, Moore DH II, Ursell PC and Jaffe RB: In utero angiopoietin-2 gene delivery remodels placental blood vessel phenotype: A murine model for studying placental angiogenesis. Mol Hum Reprod. 11:253–260. 2005. View Article : Google Scholar : PubMed/NCBI
42	Sato TN, Tozawa Y, Deutsch U, Wolburg-Buchholz K, Fujiwara Y, Gendron-Maguire M, Gridley T, Wolburg H, Risau W and Qin Y: Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature. 376:70–74. 1995. View Article : Google Scholar : PubMed/NCBI
43	Wulff C, Wilson H, Dickson SE, Wiegand SJ and Fraser HM: Hemochorial placentation in the primate: Expression of vascular endothelial growth factor, angiopoietins, and their receptors throughout pregnancy. Biol Reprod. 66:802–812. 2002. View Article : Google Scholar : PubMed/NCBI
44	Steegers EA, von Dadelszen P, Duvekot JJ and Pijnenborg R: Pre-eclampsia. Lancet. 376:631–644. 2010. View Article : Google Scholar : PubMed/NCBI
45	Kleinrouweler CE, Wiegerinck MM, Ris-Stalpers C, Bossuyt PM, van der Post JA, von Dadelszen P, Mol BW and Pajkrt E; EBM CONNECT Collaboration. Accuracy of circulating placental growth factor, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1 and soluble endoglin in the prediction of pre-eclampsia: A systematic review and meta-analysis. BJOG. 119:778–787. 2012. View Article : Google Scholar : PubMed/NCBI
46	Sung JF, Fan X, Dhal S, Dwyer BK, Jafari A, El-Sayed YY, Druzin ML and Nayak NR: Decreased circulating soluble Tie2 levels in preeclampsia may result from inhibition of vascular endothelial growth factor (VEGF) signaling. J Clin Endocrinol Metab. 96:E1148–E1152. 2011. View Article : Google Scholar : PubMed/NCBI
47	Han SY, Jun JK, Lee CH, Park JS and Syn HC: Angiopoietin-2: A promising indicator for the occurrence of severe preeclampsia. Hypertens Pregnancy. 31:189–199. 2012. View Article : Google Scholar
48	Kappou D, Sifakis S, Androutsopoulos V, Konstantinidou A, Spandidos DA and Papantoniou N: Placental mRNA expression of angiopoietins (Ang)-1, Ang-2 and their receptor Tie-2 is altered in pregnancies complicated by preeclampsia. Placenta. 35:718–723. 2014. View Article : Google Scholar : PubMed/NCBI
49	Szpera-Gozdziewicz A and Breborowicz GH: Endothelial dysfunction in the pathogenesis of pre-eclampsia. Front Biosci (Landmark Ed). 19:734–746. 2014. View Article : Google Scholar
50	Oh H, Takagi H, Suzuma K, Otani A, Matsumura M and Honda Y: Hypoxia and vascular endothelial growth factor selectively up-regulate angiopoietin-2 in bovine microvascular endothelial cells. J Biol Chem. 274:15732–15739. 1999. View Article : Google Scholar : PubMed/NCBI
51	Vuorela P, Matikainen MT, Kuusela P, Ylikorkala O, Alitalo K and Halmesmäki E: Endothelial tie receptor antigen in maternal and cord blood of healthy and preeclamptic subjects. Obstet Gynecol. 92:179–183. 1998. View Article : Google Scholar : PubMed/NCBI
52	Hirokoshi K, Maeshima Y, Kobayashi K, Matsuura E, Sugiyama H, Yamasaki Y, Masuyama H, Hiramatsu Y and Makino H: Increase of serum angiopoietin-2 during pregnancy is suppressed in women with preeclampsia. Am J Hypertens. 18:1181–1188. 2005. View Article : Google Scholar : PubMed/NCBI
53	Gotsch F, Romero R, Kusanovic JP, et al: Preeclampsia and small-for-gestational age are associated with decreased concentrations of a factor involved in angiogenesis: Soluble Tie-2. J Matern Fetal Neonatal Med. 21:389–402. 2008. View Article : Google Scholar : PubMed/NCBI
54	Bolin M, Wiberg-Itzel E, Wikström AK, Goop M, Larsson A, Olovsson M and Akerud H: Angiopoietin-1/angiopoietin-2 ratio for prediction of preeclampsia. Am J Hypertens. 22:891–895. 2009. View Article : Google Scholar : PubMed/NCBI
55	Schoofs K, Grittner U, Engels T, Pape J, Denk B, Henrich W and Verlohren S: The importance of repeated measurements of the sFlt-1/PlGF ratio for the prediction of preeclampsia and intrauterine growth restriction. J Perinat Med. 42:61–68. 2014. View Article : Google Scholar
56	Vrachnis N, Kalampokas E, Sifakis S, Vitoratos N, Kalampokas T, Botsis D and Iliodromiti Z: Placental growth factor (PlGF): A key to optimizing fetal growth. J Matern Fetal Neonatal Med. 26:995–1002. 2013. View Article : Google Scholar : PubMed/NCBI
57	Wang Y, Tasevski V, Wallace EM, Gallery ED and Morris JM: Reduced maternal serum concentrations of angiopoietin-2 in the first trimester precede intrauterine growth restriction associated with placental insufficiency. BJOG. 114:1427–1431. 2007. View Article : Google Scholar : PubMed/NCBI
58	Akolekar R, Casagrandi D, Skyfta E, Ahmed AA and Nicolaides KH: Maternal serum angiopoietin-2 at 11 to 13 weeks of gestation in hypertensive disorders of pregnancy. Prenat Diagn. 29:847–851. 2009. View Article : Google Scholar : PubMed/NCBI
59	Schneuer FJ, Roberts CL, Ashton AW, Guilbert C, Tasevski V, Morris JM and Nassar N: Angiopoietin 1 and 2 serum concentrations in first trimester of pregnancy as biomarkers of adverse pregnancy outcomes. Am J Obstet Gynecol. 210:345.e1–e9. 2014. View Article : Google Scholar
60	Findley CM, Cudmore MJ, Ahmed A and Kontos CD: VEGF induces Tie2 shedding via a phosphoinositide 3-kinase/Akt dependent pathway to modulate Tie2 signaling. Arterioscler Thromb Vasc Biol. 27:2619–2626. 2007. View Article : Google Scholar : PubMed/NCBI
61	Regnault TR, Galan HL, Parker TA and Anthony RV: Placental development in normal and compromised pregnancies- a review. Placenta. 23(Suppl A): S119–S129. 2002. View Article : Google Scholar
62	Tseng JJ, Hsu SL, Ho ES, Hsieh YT, Wen MC and Chou MM: Differential expression of angiopoietin-1, angiopoietin-2, and Tie receptors in placentas from pregnancies complicated by placenta accreta. Am J Obstet Gynecol. 194:564–571. 2006. View Article : Google Scholar : PubMed/NCBI
63	Vuorela P, Carpén O, Tulppala M and Halmesmäki E: VEGF, its receptors and the tie receptors in recurrent miscarriage. Mol Hum Reprod. 6:276–282. 2000. View Article : Google Scholar : PubMed/NCBI
64	Hall M, Gourley C, McNeish I, Ledermann J, Gore M, Jayson G, Perren T, Rustin G and Kaye S: Targeted anti-vascular therapies for ovarian cancer: current evidence. Br J Cancer. 108:250–258. 2013. View Article : Google Scholar : PubMed/NCBI
65	Gerald D, Chintharlapalli S, Augustin HG and Benjamin LE: Angiopoietin-2: an attractive target for improved antiangiogenic tumor therapy. Cancer Res. 73:1649–1657. 2013. View Article : Google Scholar : PubMed/NCBI