Journal of Surgical Research
Volume 146, Issue 2 , Pages 202-210 , 15 May 2008

Lowering Homocysteine Decreases Levels and Expression of VEGF165 and Endostatin

  • Hussein M. Atta, M.D., Ph.D.

      Affiliations

    • Department of Surgery, Faculty of Medicine, Minia University, El-Minia, Egypt
    • Corresponding Author InformationTo whom correspondence and reprint requests should be addressed at Department of Surgery, Faculty of Medicine, Minia University, El-Minia 61111, Egypt.
    • ,
  • Mahmoud A. El-Rehani, Ph.D.

      Affiliations

    • Department of Biochemistry, Faculty of Medicine, Minia University, El-Minia, Egypt
    • ,
  • Salama Abdel Raheim, M.D., Ph.D.

      Affiliations

    • Department of Biochemistry, Faculty of Medicine, Minia University, El-Minia, Egypt
    • ,
  • Abdel Moneim F. Galal, Ph.D.

      Affiliations

    • Department of Biochemistry, Faculty of Medicine, Minia University, El-Minia, Egypt

Received 15 February 2007

References 

  1. Simmons M. Angiogenesis (Where do we stand now?). Circulation. 2005;111:1556
  2. Losordo DW, Dimmeler S. Therapeutic angiogenesis and vasculogenesis for ischemic disease part I: Angiogenic cytokines. Circulation. 2004;109:2487
  3. Felmeden DC, Blann AD, Lip GYH. Angiogenesis: Basic pathophysiology and implications for disease. Eur Heart J. 2003;24:586
  4. Seko Y, Fukuda S, Nagai R. Serum levels of endostatin, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in patients with acute myocardial infarction undergoing early reperfusion therapy. Clin Sci (Lond). 2004;106:439
  5. Taylor LM, Moneta GL, Sexton GJ, et al. Prospective blinded study of the relationship between plasma homocysteine and progression of symptomatic peripheral arterial disease. J Vasc Surg. 1999;29:8
  6. van Guldener C, Stehouwer CDA. Hyperhomocysteinemia and vascular disease-a role for DNA hypomethylation?. Lancet. 2003;361:1668
  7. Lee R, Frenkel EP. Hyperhomocysteinemia and thrombosis. Hematol Oncol Clin N Am. 2003;17:85
  8. The homocysteine studies collaboration. Homocysteine and risk of ischemic heart disease and stroke: A meta-analysis. JAMA. 2002;288:2015
  9. Bostom AG, Rosenberg IH, Silbershatz H, et al. Nonfasting plasma total homocysteine levels and stroke incidence in elderly persons: The Framingham Study. Ann Intern Med. 1999;131:352
  10. Malinow MR, Bostom AG, Krauss RM. Homocyst(e)ine, diet, and cardiovascular diseases: A statement for healthcare professionals from the nutrition committee, American Heart Association. Circulation. 1999;99:178
  11. Chambers JC, Ueland PM, Wright M, et al. Investigation of relationship between reduced, oxidized, and protein-bound homocysteine and vascular endothelial function in healthy human subjects. Circ Res. 2001;89:187
  12. Chambers JC, Obeid OA, Kooner JS. Physiological increments in plasma homocysteine induce vascular endothelial dysfunction in normal human subjects. Arterioscler Thromb Vasc Biol. 1999;19:2922
  13. Bellamy MF, McDowell IFW, Ramsey MW, et al. Hyperhomocysteinemia after an oral methionine load acutely impairs endothelial function in healthy adults. Circulation. 1998;98:1848
  14. Bellamy MF, McDowell IF, Ramsey MW, et al. Oral folate enhances endothelial function in hyperhomocysteinaemic subjects. Eur J Clin Invest. 1999;29:659
  15. Chambers JC, Ueland PM, Obeid OA, Wrigley J, Refsum H, Kooner JS. Improved Vascular Endothelial Function After Oral B Vitamins An Effect Mediated Through Reduced Concentrations of Free Plasma Homocysteine. Circulation. 2000;102:2479
  16. Woo KS, Chook P, Lolin YI, et al. Folic acid improves arterial endothelial function in adults with hyperhomocystinemia. J Am Coll Cardiol. 1999;34:2002
  17. Duan J, Murohara T, Ikeda H, et al. Hyperhomocysteinemia impairs angiogenesis in response to hindlimb ischemia. Arterioscler Thromb Vasc Biol. 2000;20:2579
  18. Makin AJ, Chung NAY, Silverman SH, et al. Vascular endothelial growth factor and tissue factor in patients with established peripheral artery disease: A link between angiogenesis and thrombogenesis?. Clin Sci. 2003;104:397
  19. Roybal CN, Yang S, Sun CW, et al. Homocysteine increases the expression of vascular endothelial growth factor by a mechanism involving endoplasmic reticulum stress and transcription factor ATF4. J Biol Chem. 2004;279:14844
  20. Noma H, Funatsu H, Yamashita H, et al. Regulation of angiogenesis in diabetic retinopathy: Possible balance between vascular endothelial growth factor and endostatin. Arch Ophthalmol. 2002;120:1075
  21. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997;18:4
  22. Gaudry M, Bregerie O, Andrieu V, et al. Intracellular pool of vascular endothelial growth factor in human neutrophils. Blood. 1997;90:4153
  23. Khurana R, Simons M, Martin JF, et al. Role of angiogenesis in cardiovascular disease: A critical appraisal. Circulation. 2005;112:1813
  24. Cucina A, Borrelli V, Randone B, et al. Vascular endothelial growth factor increases the migration and proliferation of smooth muscle cells through the mediation of growth factors released by endothelial cells. J Surg Res. 2003;109:16
  25. Inoue M, Itoh H, Ueda M, et al. Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions: Possible pathophysiological significance of VEGF in progression of atherosclerosis. Circulation. 1998;98:2108
  26. Matsui K, Yoshioka T, Murakami Y, et al. Serum concentrations of vascular endothelial growth factor and monocyte-colony stimulating factor in peripheral arterial disease. Circ J. 2003;67:660
  27. Roller RE, Renner W, Dorr A, et al. Oxidative stress and increase of vascular endothelial growth factor in plasma of patients with peripheral arterial occlusive disease. Thromb Haemostasis. 2001;85:368
  28. Nakajima K, Tabata S, Yamashita T, et al. Plasma vascular endothelial growth factor level is elevated in patients with multivessel coronary artery disease. Clin Cardiol. 2004;27:281
  29. Lim HS, Lip GY, Blann AD. Angiopoietin-1 and angiopoietin-2 in diabetes mellitus: Relationship to VEGF, glycemic control, endothelial damage/dysfunction and atherosclerosis. Atherosclerosis. 2005;180:113
  30. O'Reilly MS, Boehm T, Shing Y, et al. Endostatin: Endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997;88:277
  31. Moulton KS, Heller E, Konerding MA, et al. Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation. 1999;99:1726
  32. Marneros AG, Olsen BR. Physiological role of collagen XVIII and endostatin. FASEB J. 2005;19:716
  33. Ferreras M, Felbor U, Lenhard T, et al. Generation and degradation of human endostatin proteins by various proteinases. FEBS Lett. 2000;486:247
  34. Dixelius J, Larsson H, Sasaki T, et al. Endostatin induced tyrosine kinase signaling through the Shb adaptor protein regulates endothelial cell apoptosis. Blood. 2000;95:3403
  35. Yamaguchi N, Anand-Apte B, Lee M, et al. Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding. EMBO J. 1999;18:4414
  36. Buysschaert M, Dramais A-S, Wallemacq PE, et al. Hyperhomocysteinemia in Type 2 Diabetes (Relationship to macroangiopathy, nephropathy, and insulin resistance). Diabetes Care. 2000;23:1816
  37. Quinlivan EP, McPartlin J, McNulty H, et al. Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease. Lancet. 2002;359:227
  38. Jelkmann W. Pitfalls in the measurement of circulating vascular endothelial growth factor. Clin Chem. 2001;47:617
  39. Funatsu H, Yamashita H, Noma H, et al. Outcome of vitreous surgery and the balance between vascular endothelial growth factor and endostatin. Invest Ophthalmol Vis Sci. 2003;44:1042
  40. Feldman AL, Alexander HR, Bartlett DL, et al. A prospective analysis of plasma endostatin levels in colorectal cancer patients with liver metastases. Ann Surg Oncol. 2001;8:741
  41. Feldman AL, Tamarkin L, Paciotti GF, et al. Serum endostatin levels are elevated and correlate with serum vascular endothelial growth factor levels in patients with stage IV clear cell renal cancer. Clin Cancer Res. 2000;6:4628
  42. Koehne P, Willam C, Strauss E, et al. Lack of hypoxic stimulation of VEGF secretion from neutrophils and platelets. Am J Physiol Heart Circ Physiol. 2000;279:H817
  43. Kohkichi H, Ritsuto F, Kohji M. Expression of the endostatin gene in epithelial ovarian cancer. Clin Cancer Res. 2001;7:2405
  44. Taylor LM, DeFrang RD, Harris EJ, et al. The association of elevated plasma homocyst(e)ine with progression of symptomatic peripheral arterial disease. J Vasc Surg. 1991;13:128
  45. Darius H, Pittrow D, Haberl R, et al. Are elevated homocysteine plasma levels related to peripheral arterial disease? (Results from a cross-sectional study of 6880 primary care patients). Eur J Clin Invest. 2003;33:751
  46. Malinow MR, Kang SS, Taylor LM, et al. Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease. Circulation. 1989;79:1180
  47. Chambers JC, Kooners JS. Homocysteine-an innocent bystander in vascular disease?. Eur Heart J. 2001;22:717
  48. Ciccarone E, Di Castelnuovo A, Assanelli D, et al. Homocysteine levels are associated with the severity of peripheral arterial disease in type 2 diabetic patients. J Thromb Haemost. 2003;1:2540
  49. Huang EJ, Kuo WW, Chen YJ, et al. Homocysteine and other biochemical parameters in type 2 diabetes mellitus with different diabetic duration or diabetic retinopathy. Clin Chim Acta. 2006;366:293
  50. Weiss N, Zhang Y-Y, Heydrick S, et al. Overexpression of cellular glutathione peroxidase rescues homocyst(e)ine-induced endothelial dysfunction. Proc Natl Acad Sci USA. 2001;98:12503
  51. Tawakol A, Omland T, Gerhard M, et al. Hyperhomocyst(e) inemia is associated with impaired endothelium-dependent vasodilation in humans. Circulation. 1997;95:1119
  52. Loscalzo J. The oxidant stress of hyperhomocyst(e)inemia. J Clin Invest. 1996;98:5
  53. Au-Yeung KK, Woo CW, Sung FL, et al. Hyperhomocysteinemia activates nuclear factor-κB in endothelial cells via oxidative stress. Circ Res. 2004;94:28
  54. Zhang C, Cai Y, Adachi MT, et al. Homocysteine induces programmed cell death in human vascular endothelial cells through activation of the unfolded protein response. J Biol Chem. 2001;276:35867
  55. Hossain GS, van Thienen JV, Werstuck GH, et al. TDAG51 Is induced by homocysteine, promotes detachmentmediated programmed cell death, and contributes to the development of atherosclerosis in hyperhomocysteinemia. J Biol Chem. 2003;278:30317
  56. Lee SJ, Kim KM, Namkoong S, et al. Nitric oxide inhibition of homocysteine-induced human endothelial cell apoptosis by down-regulation of p53-dependent Noxa expression through the formation of S-nitrosohomocysteine. J Biol Chem. 2005;280:5781
  57. Maeda M, Yamamoto I, Fujio Y, et al. Homocysteine induces vascular endothelial growth factor expression in differentiated THP-1 macrophages. Biochim Biophys Acta. 2003;1623:41
  58. Holven KB, Holm T, Aukrust P, et al. Effect of folic acid treatment on endothelium-dependent vasodilatation and nitric oxide-derived end products in hyperhomocysteinemic subjects. Am J Med. 2001;110:536
  59. Mangoni AA, Sherwood RA, Asonganyi B, et al. Short-term oral acid folic supplementation enhances endothelial function in patients with type 2 diabetes. Am J Hypertens. 2005;18:220
  60. Panchal VR, Rehman J, Nguyen AT, et al. Reduced pericardial levels of endostatin correlate with collateral development in patients with ischemic heart disease. J Am Coll Cardiol. 2004;43:1383
  61. Smulders YM, Rakic M, Slaats EH, et al. Fasting and post-methionine homocysteine levels in NIDDM determinants and correlations with retinopathy, albuminuria, and cardiovascular disease. Diabetes Care. 1999;22:125
  62. Aiello LP, Wong JS. Role of vascular endothelial growth factor in diabetic vascular complications. Kidney Int Suppl. 2000;77:S113
  63. Shams N, Ianchulev T. Role of vascular endothelial growth factor in ocular angiogenesis. Ophthalmol Clin N Am. 2006;19:335
  64. Looker HC, Fagot-Campagna A, Gunter EW, et al. Homocysteine as a risk factor for nephropathy and retinopathy in type 2 diabetes. Diabetologia. 2003;46:766
  65. Noma H, Funatsu H, Yamashita H, et al. Regulation of angiogenesis in diabetic retinopathy: Possible balance between vascular endothelial growth factor and endostatin. Arch Ophthalmol. 2002;120:1075
  66. Liou JY, Shyu KG, Lu MJ, et al. Pericardial fluid and serum levels of vascular endothelial growth factor and endostatin in patients with or without coronary artery disease. J Formos Med Assoc. 2006;105:377
  67. Nagashima M, Asano G, Yoshino S. Imbalance in production between vascular endothelial growth factor and endostatin in patients with rheumatoid arthritis. J Rheumatol. 2000;27:2339
  68. Kanazawa H, Hirata K, Yoshikawa J. Imbalance between vascular endothelial growth factor and endostatin in emphysema. Eur Respir J. 2003;22:609
  69. Takeshita S, Kawamura Y, Takabayashi H, et al. Imbalance in the production between vascular endothelial growth factor and endostatin in Kawasaki disease. Clin Exp Immunol. 2005;139:575
  70. Sandor Z, Deng XM, Khomenko T, et al. Altered angiogenic balance in ulcerative colitis: A key to impaired healing?. Biochem Biophys Res Commun. 2006;350:147
  71. Gruszka A, Kunert-Radek J, Pawlikowski M, et al. Serum endostatin levels are elevated and correlate with serum vascular endothelial growth factor levels in patients with pituitary adenomas. Pituitary. 2005;8:163
  72. Zhao J, Yan F, Ju H, et al. Correlation between serum vascular endothelial growth factor and endostatin levels in patients with breast cancer. Cancer Lett. 2004;204:87
  73. Uematsu S, Higashi T, Nouso K, et al. Altered expression of vascular endothelial growth factor, fibroblast growth factor-2 and endostatin in patients with hepatocellular carcinoma. J Gastroenterol Hepatol. 2005;20:583
  74. Miyashita M, Tajiri T, Yanagi K, et al. Serum levels of vascular endothelial growth factor, basic fibroblast growth factor and endostatin in human metastatic liver tumors. Hepatogastroenterology. 2003;50:308

PII: S0022-4804(07)00330-7

doi: 10.1016/j.jss.2007.04.038

Journal of Surgical Research
Volume 146, Issue 2 , Pages 202-210 , 15 May 2008

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