angiopoietin 2


Gene Symbol: angiopoietin 2
Description: angiopoietin 2
Alias: AGPT2, ANG2, angiopoietin-2, ANG-2, Tie2-ligand, angiopoietin-2B, angiopoietin-2a
Species: human
Products:     angiopoietin 2

Top Publications

  1. Feng Y, Vom Hagen F, Pfister F, Djokic S, Hoffmann S, Back W, et al. Impaired pericyte recruitment and abnormal retinal angiogenesis as a result of angiopoietin-2 overexpression. Thromb Haemost. 2007;97:99-108 pubmed
    Angiopoietin-2 (Ang2) is among the relevant growth factors induced by hypoxia and plays an important role in the initiation of retinal neovascularizations...
  2. Harfouche R, Hussain S. Signaling and regulation of endothelial cell survival by angiopoietin-2. Am J Physiol Heart Circ Physiol. 2006;291:H1635-45 pubmed
    ..We also conclude that the nature of interactions in terms of ERK1/2 activation between Ang-2 and VEGF is different from that of Ang-1 and VEGF. ..
  3. Maisonpierre P, Suri C, Jones P, Bartunkova S, Wiegand S, Radziejewski C, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997;277:55-60 pubmed
    ..An Ang1 relative, termed angiopoietin-2 (Ang2), was identified by homology screening and shown to be a naturally occurring antagonist for Ang1 and Tie2...
  4. Yuan H, Khankin E, Karumanchi S, Parikh S. Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium. Mol Cell Biol. 2009;29:2011-22 pubmed publisher
    b>Angiopoietin 2 (Ang2) was originally shown to be a competitive antagonist for Ang1 of the receptor tyrosine kinase Tie2 in endothelial cells (ECs). Since then, reports have conflicted on whether Ang2 is an agonist or antagonist of Tie2...
  5. Volkova E, Willis J, Wells J, Robinson B, Dachs G, Currie M. Association of angiopoietin-2, C-reactive protein and markers of obesity and insulin resistance with survival outcome in colorectal cancer. Br J Cancer. 2011;104:51-9 pubmed publisher
    ..The study confirms serum Ang-2 as a predictive marker for outcome of colorectal cancer. ..
  6. David S, Kümpers P, Lukasz A, Fliser D, Martens Lobenhoffer J, Bode Boger S, et al. Circulating angiopoietin-2 levels increase with progress of chronic kidney disease. Nephrol Dial Transplant. 2010;25:2571-6 pubmed publisher
    ..The correlation between Ang-2 and ADMA points towards the hypothesis that the ADMA-driven NO deficiency might trigger Ang-2 release and account for the Ang-2 increase in CKD patients. ..
  7. Tsutsui S, Inoue H, Yasuda K, Suzuki K, Takeuchi H, Nishizaki T, et al. Angiopoietin 2 expression in invasive ductal carcinoma of the breast: its relationship to the VEGF expression and microvessel density. Breast Cancer Res Treat. 2006;98:261-6 pubmed
    ..The survival analysis demonstrated a high MVD, which was induced by a high expression of both VEGF and Ang-2, to therefore have a strong prognostic significance in breast cancer. ..
  8. Srirajaskanthan R, Dancey G, Hackshaw A, Luong T, Caplin M, Meyer T. Circulating angiopoietin-2 is elevated in patients with neuroendocrine tumours and correlates with disease burden and prognosis. Endocr Relat Cancer. 2009;16:967-76 pubmed publisher
    ..04). Serum Ang-2 but not Ang-1 is elevated in NET patients. Ang-2 may be a useful serum marker for monitoring and assessment of prognosis in patients with NETs. ..
  9. Kim K, Choi H, Steinmetz M, Maco B, Kammerer R, Ahn S, et al. Oligomerization and multimerization are critical for angiopoietin-1 to bind and phosphorylate Tie2. J Biol Chem. 2005;280:20126-31 pubmed
    ..In this study, we generated several Ang1 and angiopoietin-2 (Ang2) variants to define the role of the superclustering and oligomerization domains of the Ang1 protein...

More Information


  1. Shroff R, Price K, Kolatsi Joannou M, Todd A, Wells D, Deanfield J, et al. Circulating angiopoietin-2 is a marker for early cardiovascular disease in children on chronic dialysis. PLoS ONE. 2013;8:e56273 pubmed publisher
    ..The possibility that the release of angiopoietin-2 from endothelia is mediated by urate should be explored further. ..
  2. Park J, Park K, Kim Y, Sheen S, Lee K, Lee H, et al. Serum angiopoietin-2 as a clinical marker for lung cancer. Chest. 2007;132:200-6 pubmed
    ..Our study suggests that serum angiopoietin-2 is a useful clinical marker for detecting NSCLC with distant metastasis and is of potential prognostic value. ..
  3. Kümpers P, Koenecke C, Hecker H, Hellpap J, Horn R, Verhagen W, et al. Angiopoietin-2 predicts disease-free survival after allogeneic stem cell transplantation in patients with high-risk myeloid malignancies. Blood. 2008;112:2139-48 pubmed publisher
  4. Moon W, Park H, Yu K, Jang K, Kang M, Park H, et al. Expression of angiopoietin 1, 2 and their common receptor Tie2 in human gastric carcinoma: implication for angiogenesis. J Korean Med Sci. 2006;21:272-8 pubmed
    ..These findings indicate that the expression of Ang-1 and Ang-2 is important for tumor angiogenesis, and suggest a possible role of autocrine/paracrine function of angiopoietin/Tie2 system in gastric cancer progression. ..
  5. Schliemann C, Bieker R, Padro T, Kessler T, Hintelmann H, Buchner T, et al. Expression of angiopoietins and their receptor Tie2 in the bone marrow of patients with acute myeloid leukemia. Haematologica. 2006;91:1203-11 pubmed
    ..Furthermore, high pre-therapeutic levels of Ang-2 in the bone marrow indicate a favorable prognosis in AML patients treated with polychemotherapy, although the mechanism is not yet known. ..
  6. Mofarrahi M, Nouh T, Qureshi S, Guillot L, Mayaki D, Hussain S. Regulation of angiopoietin expression by bacterial lipopolysaccharide. Am J Physiol Lung Cell Mol Physiol. 2008;294:L955-63 pubmed publisher
  7. Schiessl B, Innes B, Bulmer J, Otun H, Chadwick T, Robson S, et al. Localization of angiogenic growth factors and their receptors in the human placental bed throughout normal human pregnancy. Placenta. 2009;30:79-87 pubmed publisher
    ..These findings suggest that the Ang and VEGF families may play a role in the process of spiral artery remodelling in normal pregnancy. ..
  8. Giuliano J, Lahni P, Bigham M, Manning P, Nelson D, Wong H, et al. Plasma angiopoietin-2 levels increase in children following cardiopulmonary bypass. Intensive Care Med. 2008;34:1851-7 pubmed publisher
    ..Angpt-2 appears to be an important biomarker of adverse outcome following CPB in children. ..
  9. Lieb W, Zachariah J, Xanthakis V, Safa R, Chen M, Sullivan L, et al. Clinical and genetic correlates of circulating angiopoietin-2 and soluble Tie-2 in the community. Circ Cardiovasc Genet. 2010;3:300-6 pubmed publisher
    ..These observations are consistent with the notion that angiogenesis and vascular remodeling are determined in part by genetic influences and associated with metabolic risk factors. ..
  10. Iribarren C, Phelps B, Darbinian J, McCluskey E, Quesenberry C, Hytopoulos E, et al. Circulating angiopoietins-1 and -2, angiopoietin receptor Tie-2 and vascular endothelial growth factor-A as biomarkers of acute myocardial infarction: a prospective nested case-control study. BMC Cardiovasc Disord. 2011;11:31 pubmed publisher
    ..63-fold (95 percent confidence interval, 1.09 to 2.45) increased odds of AMI. Our data support a role of Ang-2 as a biomarker of incident AMI independent of traditional risk factors. ..
  11. Takanami I. Overexpression of Ang-2 mRNA in non-small cell lung cancer: association with angiogenesis and poor prognosis. Oncol Rep. 2004;12:849-53 pubmed
    ..0028). These data indicate that Ang-2 may contribute to tumor angiogenesis and progression and that Ang-2 gene expression can serve as a useful prognostic marker in NSCLC. ..
  12. Torimura T, Ueno T, Kin M, Harada R, Taniguchi E, Nakamura T, et al. Overexpression of angiopoietin-1 and angiopoietin-2 in hepatocellular carcinoma. J Hepatol. 2004;40:799-807 pubmed
    ..Our findings indicate that the increased expression of Angiopoietin-1 and Angiopoietin-2 play a critical role in the process of vascular development in HCC. ..
  13. Siner J, Bhandari V, Engle K, Elias J, Siegel M. Elevated serum angiopoietin 2 levels are associated with increased mortality in sepsis. Shock. 2009;31:348-53 pubmed publisher
    The vascular growth factor angiopoietin 2 (Ang-2) is known to promote inflammation and endothelial dysfunction, but its prognostic capacity and relationship to outcomes in human sepsis are unknown...
  14. Helfrich I, Edler L, Sucker A, Thomas M, Christian S, Schadendorf D, et al. Angiopoietin-2 levels are associated with disease progression in metastatic malignant melanoma. Clin Cancer Res. 2009;15:1384-92 pubmed publisher
    The blood vessel-destabilizing Tie2 ligand angiopoietin-2 (Ang-2) acts in concert with the vascular endothelial growth factor/vascular endothelial growth factor receptor system to control vessel assembly during tumor progression...
  15. Kranidioti H, Orfanos S, Vaki I, Kotanidou A, Raftogiannis M, Dimopoulou I, et al. Angiopoietin-2 is increased in septic shock: evidence for the existence of a circulating factor stimulating its release from human monocytes. Immunol Lett. 2009;125:65-71 pubmed publisher
    ..It seems that a circulating factor may exist in the serum of patients with septic shock that stimulates gene expression and subsequent release of Ang-2 from monocytes. TLR4 and TNFalpha modulate release of Ang-2. ..
  16. Anuradha S, Mohan V, Gokulakrishnan K, Dixit M. Angiopoietin-2 levels in glucose intolerance, hypertension, and metabolic syndrome in Asian Indians (Chennai Urban Rural Epidemiology Study-74). Metabolism. 2010;59:774-9 pubmed publisher
    ..001). This study demonstrates that increased levels of Ang-2 are seen in Asian Indian subjects with IGT, T2DM, and hypertension and in subjects with MS even in the absence of fasting hyperglycemia. ..
  17. Daly C, Pasnikowski E, Burova E, Wong V, Aldrich T, Griffiths J, et al. Angiopoietin-2 functions as an autocrine protective factor in stressed endothelial cells. Proc Natl Acad Sci U S A. 2006;103:15491-6 pubmed
    ..Our data suggests a model in which Ang-2 expression is induced in stressed endothelial cells, where it acts as an autocrine Tie2 agonist and protective factor. ..
  18. Thomas M, Felcht M, Kruse K, Kretschmer S, Deppermann C, Biesdorf A, et al. Angiopoietin-2 stimulation of endothelial cells induces alphavbeta3 integrin internalization and degradation. J Biol Chem. 2010;285:23842-9 pubmed publisher
    ..Taken together, the experiments define Tie2/alphavbeta3 integrin association-induced integrin internalization and degradation as mechanistic consequences of endothelial Ang-2 stimulation. ..
  19. Andersen S, Donnem T, Al Shibli K, Al Saad S, Stenvold H, Busund L, et al. Prognostic impacts of angiopoietins in NSCLC tumor cells and stroma: VEGF-A impact is strongly associated with Ang-2. PLoS ONE. 2011;6:e19773 pubmed publisher
    ..In tumor stroma, Ang-4 and Ang-2 are independently associated with survival. The prognostic impact of tumor cell VEGF-A in NSCLC appears strongly associated with a concomitantly high tumor cell expression of Ang-2. ..
  20. Michels M, van der Ven A, Djamiatun K, Fijnheer R, de Groot P, Griffioen A, et al. Imbalance of angiopoietin-1 and angiopoetin-2 in severe dengue and relationship with thrombocytopenia, endothelial activation, and vascular stability. Am J Trop Med Hyg. 2012;87:943-6 pubmed publisher
    ..Dengue-associated thrombocytopenia and endothelial activation are associated with an imbalance in angiopoietin-2: angiopoietin-1 plasma levels. This imbalance may contribute to the transient plasma leakage in DHF/DSS. ..
  21. Witzenbichler B, Maisonpierre P, Jones P, Yancopoulos G, Isner J. Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial-specific receptor tyrosine kinase Tie2. J Biol Chem. 1998;273:18514-21 pubmed
  22. Lemieux C, Maliba R, Favier J, Théorêt J, Merhi Y, Sirois M. Angiopoietins can directly activate endothelial cells and neutrophils to promote proinflammatory responses. Blood. 2005;105:1523-30 pubmed
    Angiopoietin-1 (Ang1) and -2 (Ang2) are endothelial growth factors that bind to the tyrosine kinase receptor Tie2 and contribute to orchestrate blood vessel formation during angiogenesis...
  23. Zhang L, Yang N, Park J, Katsaros D, Fracchioli S, Cao G, et al. Tumor-derived vascular endothelial growth factor up-regulates angiopoietin-2 in host endothelium and destabilizes host vasculature, supporting angiogenesis in ovarian cancer. Cancer Res. 2003;63:3403-12 pubmed
  24. Pichiule P, Chavez J, Lamanna J. Hypoxic regulation of angiopoietin-2 expression in endothelial cells. J Biol Chem. 2004;279:12171-80 pubmed
    Exposure of endothelial cells to hypoxia-induced angiopoietin-2 (Ang2) expression. The increase in Ang2 mRNA levels occurred by transcriptional regulation and by post-transcriptional increase in mRNA stability...
  25. Hirokoshi K, Maeshima Y, Kobayashi K, Matsuura E, Sugiyama H, Yamasaki Y, et al. Increase of serum angiopoietin-2 during pregnancy is suppressed in women with preeclampsia. Am J Hypertens. 2005;18:1181-8 pubmed
  26. Falcon B, Hashizume H, Koumoutsakos P, Chou J, Bready J, Coxon A, et al. Contrasting actions of selective inhibitors of angiopoietin-1 and angiopoietin-2 on the normalization of tumor blood vessels. Am J Pathol. 2009;175:2159-70 pubmed publisher
    Angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) have complex actions in angiogenesis and vascular remodeling due to their effects on Tie2 receptor signaling...
  27. Li C, Sun C, Fan J, Geng N, Li C, Liao J, et al. Angiopoietin-2 expression is correlated with angiogenesis and overall survival in oral squamous cell carcinoma. Med Oncol. 2013;30:571 pubmed publisher
    ..Expression of Ang-2 was associated with angiogenesis and vessel maturation in OSCC. Further studies will evaluate the prognostic value of determining Ang-2 expression in OSCC. ..
  28. Ochiumi T, Tanaka S, Oka S, Hiyama T, Ito M, Kitadai Y, et al. Clinical significance of angiopoietin-2 expression at the deepest invasive tumor site of advanced colorectal carcinoma. Int J Oncol. 2004;24:539-47 pubmed
  29. Schulz P, Fischer C, Detjen K, Rieke S, Hilfenhaus G, Von Marschall Z, et al. Angiopoietin-2 drives lymphatic metastasis of pancreatic cancer. FASEB J. 2011;25:3325-35 pubmed publisher
    ..0005). These findings indicate that Ang-2 participates in the control of lymphatic metastasis, constitutes a noninvasive prognostic biomarker, and may provide an accessible therapeutic target in PDAC. ..
  30. Sallinen H, Heikura T, Laidinen S, Kosma V, Heinonen S, Yla Herttuala S, et al. Preoperative angiopoietin-2 serum levels: a marker of malignant potential in ovarian neoplasms and poor prognosis in epithelial ovarian cancer. Int J Gynecol Cancer. 2010;20:1498-505 pubmed publisher
    ..These results also suggest that Ang-2 may serve as an angiogenic marker of decreased patient survival in ovarian cancer. ..
  31. Fiedler U, Scharpfenecker M, Koidl S, Hegen A, Grunow V, Schmidt J, et al. The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. Blood. 2004;103:4150-6 pubmed
  32. Hegen A, Koidl S, Weindel K, Marme D, Augustin H, Fiedler U. Expression of angiopoietin-2 in endothelial cells is controlled by positive and negative regulatory promoter elements. Arterioscler Thromb Vasc Biol. 2004;24:1803-9 pubmed
  33. Seval Y, Sati L, Celik Ozenci C, Taskin O, Demir R. The distribution of angiopoietin-1, angiopoietin-2 and their receptors tie-1 and tie-2 in the very early human placenta. Placenta. 2008;29:809-15 pubmed publisher
  34. Giamarellos Bourboulis E, Kanellakopoulou K, Pelekanou A, Tsaganos T, Kotzampassi K. Kinetics of angiopoietin-2 in serum of multi-trauma patients: correlation with patient severity. Cytokine. 2008;44:310-3 pubmed publisher
    ..00 (p=0.037). Serum levels of Ang-2 in multi-trauma patients are increased upon advent of septic complications and they are connected with bad prognosis. Its exact role in the process of multiple trauma remains to be defined. ..
  35. Hata K, Udagawa J, Fujiwaki R, Nakayama K, Otani H, Miyazaki K. Expression of angiopoietin-1, angiopoietin-2, and Tie2 genes in normal ovary with corpus luteum and in ovarian cancer. Oncology. 2002;62:340-8 pubmed
    The recent discovery of angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) has provided novel and important insights into the molecular mechanisms of blood vessel formation...
  36. Murdoch C, Tazzyman S, Webster S, Lewis C. Expression of Tie-2 by human monocytes and their responses to angiopoietin-2. J Immunol. 2007;178:7405-11 pubmed
    ..In sum, our data indicate that Ang-2 may recruit Tie-2(+) monocytes to tumors and sites of inflammation, modulate their release of important cytokines and stimulate them to express a proangiogenic phenotype. ..
  37. Koh Y, Kim H, Hwang S, Lee J, Oh N, Jung K, et al. Double antiangiogenic protein, DAAP, targeting VEGF-A and angiopoietins in tumor angiogenesis, metastasis, and vascular leakage. Cancer Cell. 2010;18:171-84 pubmed publisher
    ..Thus, simultaneous blockade of VEGF-A and angiopoietins with DAAP is an effective therapeutic strategy for blocking tumor angiogenesis, metastasis, and vascular leakage. ..
  38. Lee H, Cho C, Hwang S, Choi H, Kim K, Ahn S, et al. Biological characterization of angiopoietin-3 and angiopoietin-4. FASEB J. 2004;18:1200-8 pubmed
    The angiopoietin (Ang) family of growth factors includes Ang1, Ang2, Ang3, and Ang4, all of which bind to the endothelial receptor tyrosine kinase Tie2. Ang3 (mouse) and Ang4 (human) are interspecies orthologs...
  39. Meyer N, Li M, Feng R, Bradfield J, Gallop R, Bellamy S, et al. ANGPT2 genetic variant is associated with trauma-associated acute lung injury and altered plasma angiopoietin-2 isoform ratio. Am J Respir Crit Care Med. 2011;183:1344-53 pubmed publisher
    ..sites in linkage disequilibrium with rs1868554, and immunoblots showed higher proportion of variant angiopoietin-2 (ANG2) isoform associated with rs1868554T (0.81 vs. 0.48; P = 0.038)...
  40. Huang Y, Li J, Hu L, Lee M, Karpatkin S. Thrombin induces increased expression and secretion of angiopoietin-2 from human umbilical vein endothelial cells. Blood. 2002;99:1646-50 pubmed
    ..Thus, thrombin-induced tumorigenesis and metastasis is associated with enhanced Ang-2 protein synthesis and secretion via enhanced transcription of Ang-2. This could help explain how thrombin promotes angiogenesis. ..
  41. Lim H, Blann A, Chong A, Freestone B, Lip G. Plasma vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in diabetes: implications for cardiovascular risk and effects of multifactorial intervention. Diabetes Care. 2004;27:2918-24 pubmed
    ..Intensive multifactorial intervention is associated with reductions in plasma VEGF, vWf, and (in patients without CVD) Ang-2 levels, possibly reflecting an improved vascular profile with treatment. ..
  42. Rennel E, Regula J, Harper S, Thomas M, Klein C, Bates D. A human neutralizing antibody specific to Ang-2 inhibits ocular angiogenesis. Microcirculation. 2011;18:598-607 pubmed publisher
    ..contributor to ocular as well as neoplastic diseases, is stimulated by endothelial production of angiopoietin-2 (Ang2). Our objective was to determine the requirement of ocular angiogenesis for Ang2 in animal models of disease...
  43. Nakayama T, Inaba M, Naito S, Mihara Y, Miura S, Taba M, et al. Expression of angiopoietin-1, 2 and 4 and Tie-1 and 2 in gastrointestinal stromal tumor, leiomyoma and schwannoma. World J Gastroenterol. 2007;13:4473-9 pubmed
    ..Our results suggest that the angiopoietin pathway plays an important role in the differentiation of GISTs, leiomyomas and schwannomas. ..
  44. Barton W, Tzvetkova D, Nikolov D. Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition. Structure. 2005;13:825-32 pubmed
    ..4 A crystal structure of the Angiopoietin-2 (Ang2) receptor binding region. The structure reveals a fibrinogen fold with a unique C-terminal P domain...
  45. Parikh S, Mammoto T, Schultz A, Yuan H, Christiani D, Karumanchi S, et al. Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans. PLoS Med. 2006;3:e46 pubmed
    ..Last, we show that excess systemic Ang-2 provokes pulmonary leak and congestion in otherwise healthy adult mice. Our results identify a critical role for Ang-2 in disrupting normal pulmonary endothelial function. ..
  46. Imanishi Y, Hu B, Xiao G, Yao X, Cheng S. Angiopoietin-2, an angiogenic regulator, promotes initial growth and survival of breast cancer metastases to the lung through the integrin-linked kinase (ILK)-AKT-B cell lymphoma 2 (Bcl-2) pathway. J Biol Chem. 2011;286:29249-60 pubmed publisher
    ..We previously reported that angiopoietin-2 (Ang2), an angiogenic regulator stimulates MCF-7 breast tumor metastasis from their orthotopic sites to distant organs ..
  47. Leow C, Coffman K, Inigo I, Breen S, Czapiga M, Soukharev S, et al. MEDI3617, a human anti-angiopoietin 2 monoclonal antibody, inhibits angiogenesis and tumor growth in human tumor xenograft models. Int J Oncol. 2012;40:1321-30 pubmed publisher
    b>Angiopoietin 2 (Ang2) is an important regulator of angiogenesis, blood vessel maturation and integrity of the vascular endothelium...
  48. Silver K, Zhong K, Leke R, Taylor D, Kain K. Dysregulation of angiopoietins is associated with placental malaria and low birth weight. PLoS ONE. 2010;5:e9481 pubmed publisher
    ..falciparum-infected mothers at risk of LBW deliveries. ..
  49. Naumnik W, Naumnik B, Niewiarowska K, Ossolinska M, Chyczewska E. Angiogenic axis angiopoietin-1 and angiopoietin-2/Tie-2 in non-small cell lung cancer: a bronchoalveolar lavage and serum study. Adv Exp Med Biol. 2013;788:341-8 pubmed publisher
    ..We conclude that the angiogenic axis Ang-1 and Ang-2/Tie-2 may play an important role in lung cancer development and their concentrations may be a useful marker at the time of initial diagnosis of lung cancer. ..
  50. Hu B, Jarzynka M, Guo P, Imanishi Y, Schlaepfer D, Cheng S. Angiopoietin 2 induces glioma cell invasion by stimulating matrix metalloprotease 2 expression through the alphavbeta1 integrin and focal adhesion kinase signaling pathway. Cancer Res. 2006;66:775-83 pubmed
    Accumulating evidence reveals a significant correlation between angiopoietin 2 (Ang2) expression and tumor invasion and metastasis in various human cancers, but the major focus of recent studies has been on the angiogenic effects of Ang2...
  51. Hou H, Chou W, Lin L, Tang J, Tseng M, Huang C, et al. Expression of angiopoietins and vascular endothelial growth factors and their clinical significance in acute myeloid leukemia. Leuk Res. 2008;32:904-12 pubmed
    ..Subgroup analysis showed that Ang-2 expression had prognostic impact on patients with low (but not high) Ang-1 or Tie2 levels, and on patients with high (but not low) VEGF-A or VEGF-C levels. ..
  52. Giuliano J, Lahni P, Harmon K, Wong H, Doughty L, Carcillo J, et al. Admission angiopoietin levels in children with septic shock. Shock. 2007;28:650-654 pubmed
    ..Given the contrasting effects of angpt-2 and angpt-1 on the vascular endothelium, these two factors may play an important role in the pathophysiology of septic shock in children, and further studies are warranted. ..
  53. Detjen K, Rieke S, Deters A, Schulz P, Rexin A, Vollmer S, et al. Angiopoietin-2 promotes disease progression of neuroendocrine tumors. Clin Cancer Res. 2010;16:420-9 pubmed publisher
    ..0003). Induction of Ang-2 in neuroendocrine tumors represents a clinically relevant pathomechanism of disease progression and constitutes an adverse prognostic marker. ..
  54. Oliner J, Min H, Leal J, Yu D, Rao S, You E, et al. Suppression of angiogenesis and tumor growth by selective inhibition of angiopoietin-2. Cancer Cell. 2004;6:507-16 pubmed
    Angiopoietin-2 (Ang2) exhibits broad expression in the remodeling vasculature of human tumors but very limited expression in normal tissues, making it an attractive candidate target for antiangiogenic cancer therapy...
  55. Davis J, Yeo T, Piera K, Woodberry T, Celermajer D, Stephens D, et al. Angiopoietin-2 is increased in sepsis and inversely associated with nitric oxide-dependent microvascular reactivity. Crit Care. 2010;14:R89 pubmed publisher
    ..Agents that increase endothelial NO bioavailability or inhibit WPB exocytosis and/or Ang-2 activity may have therapeutic potential in sepsis. ..
  56. Fiedler U, Krissl T, Koidl S, Weiss C, Koblizek T, Deutsch U, et al. 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. 2003;278:1721-7 pubmed
  57. Sie M, Wagemakers M, Molema G, Mooij J, de Bont E, den Dunnen W. The angiopoietin 1/angiopoietin 2 balance as a prognostic marker in primary glioblastoma multiforme. J Neurosurg. 2009;110:147-55 pubmed publisher
    ..The authors' findings support the need for further studies of the feasibility of antiangiogenic therapy in primary GBMs, with a special focus on the normalization of tumor vasculature. ..
  58. Coffelt S, Chen Y, Muthana M, Welford A, Tal A, Scholz A, et al. Angiopoietin 2 stimulates TIE2-expressing monocytes to suppress T cell activation and to promote regulatory T cell expansion. J Immunol. 2011;186:4183-90 pubmed publisher
    b>Angiopoietin 2 (ANGPT2) is a proangiogenic cytokine whose expression is often upregulated by endothelial cells in tumors...
  59. Yeo T, Lampah D, Gitawati R, Tjitra E, Kenangalem E, Piera K, et al. Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria. Proc Natl Acad Sci U S A. 2008;105:17097-102 pubmed publisher
    ..Agents that improve endothelial NO, reduce WPB exocytosis, and/or antagonize Ang-2 may have therapeutic roles in SM. ..
  60. Lukasz A, Hellpap J, Horn R, Kielstein J, David S, Haller H, et al. Circulating angiopoietin-1 and angiopoietin-2 in critically ill patients: development and clinical application of two new immunoassays. Crit Care. 2008;12:R94 pubmed publisher
    ..According to preclinical and clinical validation, circulating Ang-1 and Ang-2 can be reliably assessed by novel immunoassays in the intensive care unit setting. ..
  61. Gerald D, Chintharlapalli S, Augustin H, Benjamin L. Angiopoietin-2: an attractive target for improved antiangiogenic tumor therapy. Cancer Res. 2013;73:1649-57 pubmed publisher
    ..Angiopoietin-2 (Ang2) appears to be a particularly attractive therapeutic target...
  62. Procopio W, Pelavin P, Lee W, Yeilding N. Angiopoietin-1 and -2 coiled coil domains mediate distinct homo-oligomerization patterns, but fibrinogen-like domains mediate ligand activity. J Biol Chem. 1999;274:30196-201 pubmed
  63. Patel J, Lim H, Varughese G, Hughes E, Lip G. Angiopoietin-2 levels as a biomarker of cardiovascular risk in patients with hypertension. Ann Med. 2008;40:215-22 pubmed publisher
    ..Among patients with hypertension, raised levels of Ang-2 were predictive of MI, and further study is warranted to evaluate the use of this biomarker in CVD management, risk stratification, and prevention. ..
  64. Geva E, Ginzinger D, Zaloudek C, Moore D, Byrne A, Jaffe R. 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. 2002;87:4213-24 pubmed
    ..5 (not significant) and 2.8%/wk (P = 0.034), respectively, whereas Ang2 decreased logarithmically by 3.5%/wk (P = 0.0003)...
  65. Zhou Y, Bellingard V, Feng K, McMaster M, Fisher S. Human cytotrophoblasts promote endothelial survival and vascular remodeling through secretion of Ang2, PlGF, and VEGF-C. Dev Biol. 2003;263:114-25 pubmed
    ..The data show that cytotrophoblasts predominantly expressed Ang2. We also studied the paracrine functions of Ang2 and the VEGFs by culturing uterine microvascular endothelial cells ..
  66. Lovegrove F, Tangpukdee N, Opoka R, Lafferty E, Rajwans N, Hawkes M, et al. Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children. PLoS ONE. 2009;4:e4912 pubmed publisher
    ..027). ANG-1 and the ANG-2/1 ratio are promising clinically informative biomarkers for CM. Additional studies should address their utility as prognostic biomarkers and potential therapeutic targets in severe malaria. ..
  67. van der Heijden M, Pickkers P, van Nieuw Amerongen G, van Hinsbergh V, Bouw M, Van Der Hoeven J, et al. Circulating angiopoietin-2 levels in the course of septic shock: relation with fluid balance, pulmonary dysfunction and mortality. Intensive Care Med. 2009;35:1567-74 pubmed publisher
    ..In contrast to VWF, plasma angiopoietin-2 positively relates to fluid balance, pulmonary dysfunction and mortality throughout the course of septic shock, in line with a suggested mediator role of the protein. ..
  68. Lim H, Lip G, Blann A. Angiopoietin-1 and angiopoietin-2 in diabetes mellitus: relationship to VEGF, glycaemic control, endothelial damage/dysfunction and atherosclerosis. Atherosclerosis. 2005;180:113-8 pubmed
    ..VEGF is likely to have a more prominent role in diabetes than Ang-2. ..
  69. Felcht M, Luck R, Schering A, Seidel P, Srivastava K, Hu J, et al. Angiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling. J Clin Invest. 2012;122:1991-2005 pubmed publisher
    ..The results of this study have immediate translational implications for the therapeutic exploitation of angiopoietin signaling. ..
  70. Daly C, Eichten A, Castanaro C, Pasnikowski E, Adler A, Lalani A, et al. Angiopoietin-2 functions as a Tie2 agonist in tumor models, where it limits the effects of VEGF inhibition. Cancer Res. 2013;73:108-18 pubmed publisher
    The angiopoietins Ang1 (ANGPT1) and Ang2 (ANGPT2) are secreted factors that bind to the endothelial cell-specific receptor tyrosine kinase Tie2 (TEK) and regulate angiogenesis...
  71. Eleuteri E, Di Stefano A, Tarro Genta F, Vicari C, Gnemmi I, Colombo M, et al. Stepwise increase of angiopoietin-2 serum levels is related to haemodynamic and functional impairment in stable chronic heart failure. Eur J Cardiovasc Prev Rehabil. 2011;18:607-14 pubmed publisher
    ..94 (95% CI 0.88-0.99; p?<?0.001). These data demonstrate that angiopoietin-2 and selected serum markers of angiogenesis progressively increase with haemodynamic and functional decline in CHF. ..
  72. Krausz S, Garcia S, Ambarus C, de Launay D, Foster M, Naiman B, et al. Angiopoietin-2 promotes inflammatory activation of human macrophages and is essential for murine experimental arthritis. Ann Rheum Dis. 2012;71:1402-10 pubmed publisher
    ..Ang-2 makes requisite contributions to pathology in CIA, indicating that targeting Ang-2 may be of therapeutic benefit in the treatment of RA. ..
  73. Tanaka S, Mori M, Sakamoto Y, Makuuchi M, Sugimachi K, Wands J. Biologic significance of angiopoietin-2 expression in human hepatocellular carcinoma. J Clin Invest. 1999;103:341-5 pubmed
    ..The full coding sequence of a variant angiopoietin-2 (Ang2) cDNA was obtained from HCC specimens, and the biologic consequences of overexpression on tumor formation and ..
  74. Mitsuhashi N, Shimizu H, Ohtsuka M, Wakabayashi Y, Ito H, Kimura F, et al. Angiopoietins and Tie-2 expression in angiogenesis and proliferation of human hepatocellular carcinoma. Hepatology. 2003;37:1105-13 pubmed
    ..In conclusion, an increased expression of Ang-2/1 in the presence of VEGF may play a critical role in promoting tumor angiogenesis and progression in human HCC. ..