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Gene Review

ANG  -  angiogenin, ribonuclease, RNase A family, 5

Homo sapiens

Synonyms: ALS9, Angiogenin, HEL168, RAA1, RNASE4, ...
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Disease relevance of ANG

  • Levels of soluble ANG were elevated in RA (351 +/- 25.7 ng/ml, p < 0.001), in RAEB/RAEB-t (402 +/- 17.9 ng/ml; p < 0.001), in CMML (413.8 +/- 29.5 ng/ml; p < 0.001), and in patients with AML (305.1 +/- 17.1 ng/ml; p < 0.01, controls 255.4 +/- 8.1 ng/ml) [1].
  • In this study, we examined the regulation of VEGF expression in vascular smooth muscle cells (VSMC) by hyperglycemia as well as by angiotensin II (ANG II) [2].
  • We also proved that another tumorigenic androgen receptor-positive prostate cancer cell line, 22Rv1, secretes higher levels of ANG than VEGF [3].
  • BACKGOUND: The distribution of angiogenin (ANG) in normal colorectal and colorectal cancer tissues has not been precisely elucidated, while studies on the clinical significance of ANG have been scanty at best [4].
  • ANG in RA SF was 248.7 +/- 17.4 ng/ml, which did not differ significantly from levels found in osteoarthritis (OA; 305.9 +/- 23.1 ng/ml) [5].
  • Angiogenin is related to worsening heart failure severity (NYHA classification), with the highest levels in NYHA class III [6].

Psychiatry related information on ANG


High impact information on ANG


Chemical compound and disease context of ANG


Biological context of ANG


Anatomical context of ANG

  • The mainstays of therapy, glycemic control and inhibition of ANG II, are key measures to prevent early podocyte injury and the subsequent development of diabetic nephropathy [23].
  • Persistent activation of the ANG/Tie-2 system in addition to high levels of VEGF may keep the vasculature in a destabilized condition and may account for the continuous formation of new and immature blood vessels resulting in massive plasma extravasation and repeated bleeding episodes [24].
  • Synovial lining cells, macrophages, endothelial cells, and vascular smooth muscle cells were immunopositive for bFGF and ANG; however, their expression was not up-regulated in RA ST compared to ST from OA and normal subjects [5].
  • ANG immunoreactivity was also observed in interstitial cells in the vicinity of and at the invasion front of cancer cells, as well as in normal superficial epithelial cells and in some interstitial cells [4].
  • It may be that some of these mediators, like ANG, play a role in the physiology of normal synovium [5].

Associations of ANG with chemical compounds

  • We also examined whether the 12-lipoxygenase (12-LO) product 12-hydroxyeicosatetraenoic acid (12-HETE) can alter VEGF expression, since 12-LO products of arachidonic acid have angiogenic properties, and ANG II as well as high glucose (HG, 25 mM) can increase 12-LO activity and expression in VSMC [2].
  • The RAS exerts its effects by the generation of a family of bioactive angiotensin peptides in which angiotensin II (ANG II) and the angiotensin type 1 (AT1) and angiotensin type 2 (AT2) receptors are most well characterised [25].
  • Here we have used computational docking as a guide for the identification of available NSC-65828 and C-181431 analogues that bind more tightly to ANG, and for the characterization of inhibitor binding modes [26].
  • Application of losartan intracerebroventricularly (i.c.v.) at 0.5 mg/kg suppressed central ANG II-stimulated plasma AVP release [27].
  • Central ANG II induced fetal plasma vasopressin increase was not altered by PD123319 [27].

Physical interactions of ANG

  • The augmented intrarenal ANG II coupled with sustained levels of AT1 receptors contribute to the continued ANG II dependent suppression of renal function and sodium excretion thereby maintaining the hypertension [28].
  • ANG II had no effect on the binding of EGF to the high-affinity receptor from 1 to 20 h and did not alter receptor downregulation [29].

Enzymatic interactions of ANG

  • ANG II increased (P < 0.05) phosphorylated ERK1/2 protein levels [30].

Regulatory relationships of ANG

  • Furthermore, ANG II treatment significantly induced VEGF mRNA and protein expression only in VSMC cultured in HG and not NG [2].
  • The current studies were undertaken to verify whether vascular response to ANG II is increased in adult offspring of low-protein fed dams (LP) compared with control (CTRL) and if so, to examine underlying mechanism(s) [31].
  • Tumor necrosis factor reduced ANG II- and potassium-induced aldosterone synthesis and CYP11B2 mRNA levels [32].
  • ANG II induces secretion and activation of transforming growth factor-beta (TGF-beta) by glomerular mesangial cells [33].
  • Furthermore, ANG II-induced TSP-1 production is dependent on p38 MAPK and JNK signaling [33].

Other interactions of ANG


Analytical, diagnostic and therapeutic context of ANG


  1. Blood levels of angiogenin and vascular endothelial growth factor are elevated in myelodysplastic syndromes and in acute myeloid leukemia. Brunner, B., Gunsilius, E., Schumacher, P., Zwierzina, H., Gastl, G., Stauder, R. J. Hematother. Stem Cell Res. (2002) [Pubmed]
  2. Effects of high glucose on vascular endothelial growth factor expression in vascular smooth muscle cells. Natarajan, R., Bai, W., Lanting, L., Gonzales, N., Nadler, J. Am. J. Physiol. (1997) [Pubmed]
  3. Highly tumorigenic human androgen receptor-positive prostate cancer cells overexpress angiogenin. Kawada, M., Inoue, H., Arakawa, M., Takamoto, K., Masuda, T., Ikeda, D. Cancer Sci. (2007) [Pubmed]
  4. Distribution of angiogenin and its gene message in colorectal cancer patients and their clinical relevance. Shimoyama, S., Shimizu, N., Tsuji, E., Yamasaki, K., Kawahara, M., Kaminishi, M. Anticancer Res. (2002) [Pubmed]
  5. Expression of basic fibroblast growth factor and angiogenin in arthritis. Hosaka, S., Shah, M.R., Barquin, N., Haines, G.K., Koch, A.E. Pathobiology (1995) [Pubmed]
  6. Elevated angiogenin levels in chronic heart failure. Patel, J.V., Sosin, M., Gunarathne, A., Hussain, I., Davis, R.C., Hughes, E.A., Lip, G.Y. Ann. Med. (2008) [Pubmed]
  7. Angiotensin II receptors and functional correlates. Timmermans, P.B., Benfield, P., Chiu, A.T., Herblin, W.F., Wong, P.C., Smith, R.D. Am. J. Hypertens. (1992) [Pubmed]
  8. Plasma renin system during exercise in normal men. Staessen, J., Fagard, R., Hespel, P., Lijnen, P., Vanhees, L., Amery, A. J. Appl. Physiol. (1987) [Pubmed]
  9. Post-traumatic stress disorder and the MMPI-2. Munley, P.H., Bains, D.S., Bloem, W.D., Busby, R.M. Journal of traumatic stress. (1995) [Pubmed]
  10. Control of aldosterone secretion: a model for convergence in cellular signaling pathways. Spät, A., Hunyady, L. Physiol. Rev. (2004) [Pubmed]
  11. ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. Greenway, M.J., Andersen, P.M., Russ, C., Ennis, S., Cashman, S., Donaghy, C., Patterson, V., Swingler, R., Kieran, D., Prehn, J., Morrison, K.E., Green, A., Acharya, K.R., Brown, R.H., Hardiman, O. Nat. Genet. (2006) [Pubmed]
  12. The renin-angiotensin system in nonmammalian vertebrates. Wilson, J.X. Endocr. Rev. (1984) [Pubmed]
  13. Microvascular rarefaction and decreased angiogenesis in rats with fetal programming of hypertension associated with exposure to a low-protein diet in utero. Pladys, P., Sennlaub, F., Brault, S., Checchin, D., Lahaie, I., Lê, N.L., Bibeau, K., Cambonie, G., Abran, D., Brochu, M., Thibault, G., Hardy, P., Chemtob, S., Nuyt, A.M. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2005) [Pubmed]
  14. Proinflammatory effects of oxidative stress in chronic kidney disease: role of additional angiotensin II blockade. Agarwal, R. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  15. Angiotensin II mediates LDL-induced superoxide generation in mesangial cells. Park, S.Y., Song, C.Y., Kim, B.C., Hong, H.K., Lee, H.S. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  16. Prostaglandin E2, renin and angiotensin II in renovascular hypertension. Kuylenstierna, J., Karlberg, B.E., Morales, O. J. Hypertens. (1984) [Pubmed]
  17. Coronary vasoconstrictor influence of angiotensin II is reduced in remodeled myocardium after myocardial infarction. Merkus, D., Haitsma, D.B., Sorop, O., Boomsma, F., de Beer, V.J., Lamers, J.M., Verdouw, P.D., Duncker, D.J. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  18. A novel candidate region for ALS on chromosome 14q11.2. Greenway, M.J., Alexander, M.D., Ennis, S., Traynor, B.J., Corr, B., Frost, E., Green, A., Hardiman, O. Neurology (2004) [Pubmed]
  19. The crystal structure of human angiogenin in complex with an antitumor neutralizing antibody. Chavali, G.B., Papageorgiou, A.C., Olson, K.A., Fett, J.W., Hu, G., Shapiro, R., Acharya, K.R. Structure (Camb.) (2003) [Pubmed]
  20. Soluble selectins, sICAM, sVCAM, and angiogenic proteins in different activity groups of patients with inflammatory bowel disease. Magro, F., Araujo, F., Pereira, P., Meireles, E., Diniz-Ribeiro, M., Velosom, F.T. Dig. Dis. Sci. (2004) [Pubmed]
  21. Hypoxia-induced up-regulation of angiogenin in human malignant melanoma. Hartmann, A., Kunz, M., Köstlin, S., Gillitzer, R., Toksoy, A., Bröcker, E.B., Klein, C.E. Cancer Res. (1999) [Pubmed]
  22. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Mehta, P.K., Griendling, K.K. Am. J. Physiol., Cell Physiol. (2007) [Pubmed]
  23. From the periphery of the glomerular capillary wall toward the center of disease: podocyte injury comes of age in diabetic nephropathy. Wolf, G., Chen, S., Ziyadeh, F.N. Diabetes (2005) [Pubmed]
  24. Increased mRNA expression of VEGF within the hematoma and imbalance of angiopoietin-1 and -2 mRNA within the neomembranes of chronic subdural hematoma. Hohenstein, A., Erber, R., Schilling, L., Weigel, R. J. Neurotrauma (2005) [Pubmed]
  25. Angiotensin and bradykinin: targets for the treatment of vascular and neuro-glial pathology in diabetic retinopathy. Wilkinson-Berka, J.L., Fletcher, E.L. Curr. Pharm. Des. (2004) [Pubmed]
  26. Identification of small-molecule inhibitors of human angiogenin and characterization of their binding interactions guided by computational docking. Jenkins, J.L., Shapiro, R. Biochemistry (2003) [Pubmed]
  27. Effects of i.c.v. losartan on the angiotensin II-mediated vasopressin release and hypothalamic fos expression in near-term ovine fetuses. Shi, L., Mao, C., Wu, J., Morrissey, P., Lee, J., Xu, Z. Peptides (2006) [Pubmed]
  28. Intrarenal angiotensin II augmentation in angiotensin II dependent hypertension. Navar, L.G., Harrison-Bernard, L.M. Hypertens. Res. (2000) [Pubmed]
  29. EGF-induced mitogenesis in proximal tubular cells: potentiation by angiotensin II. Norman, J., Badie-Dezfooly, B., Nord, E.P., Kurtz, I., Schlosser, J., Chaudhari, A., Fine, L.G. Am. J. Physiol. (1987) [Pubmed]
  30. Angiotensin II elevates nitric oxide synthase 3 expression and nitric oxide production via a mitogen-activated protein kinase cascade in ovine fetoplacental artery endothelial cells. Zheng, J., Wen, Y., Chen, D.B., Bird, I.M., Magness, R.R. Biol. Reprod. (2005) [Pubmed]
  31. Exaggerated vasomotor response to ANG II in rats with fetal programming of hypertension associated with exposure to a low-protein diet during gestation. Yzydorczyk, C., Gobeil, F., Cambonie, G., Lahaie, I., Lê, N.L., Samarani, S., Ahmad, A., Lavoie, J.C., Oligny, L.L., Pladys, P., Hardy, P., Nuyt, A.M. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  32. Regulation of aldosterone synthase in human vascular endothelial cells by angiotensin II and adrenocorticotropin. Takeda, Y., Miyamori, I., Yoneda, T., Hatakeyama, H., Inaba, S., Furukawa, K., Mabuchi, H., Takeda, R. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  33. Angiotensin II induces thrombospondin-1 production in human mesangial cells via p38 MAPK and JNK: a mechanism for activation of latent TGF-beta1. Naito, T., Masaki, T., Nikolic-Paterson, D.J., Tanji, C., Yorioka, N., Kohno, N. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  34. Hypoxic conditions stimulate the production of angiogenin and vascular endothelial growth factor by human renal proximal tubular epithelial cells in culture. Nakamura, M., Yamabe, H., Osawa, H., Nakamura, N., Shimada, M., Kumasaka, R., Murakami, R., Fujita, T., Osanai, T., Okumura, K. Nephrol. Dial. Transplant. (2006) [Pubmed]
  35. Selective abolition of pancreatic RNase binding to its inhibitor protein. Kumar, K., Brady, M., Shapiro, R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
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