Skip to main content
Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;6(1):13–24. doi: 10.1111/j.1582-4934.2002.tb00308.x

Potentiation of angiogenic response by ischemic and hypoxic reconditioning of the heart

Nilanjana Maulik 1,, D K Das 1
PMCID: PMC6740104  PMID: 12003666

Abstract

This review is intended to discuss the newly discovered role of preconditioning which should make it an attractive therapeutic stimulus for repairing the injured myocardium. We recently found that apart from rendering the myocardium tolerant to ischemic reperfusion injury, preconditioning also potentiates angiogenesis. Our study demonstrated for the first time that both ischemic and hypoxic preconditioning triggered myocardial angiogenesis at the capillary and arteriolar levels which nicely corroborated with the improved myocardial contractile function.Hypoxic preconditioning resulted in the stimulation of VEGF, the most potent angiogenic factor known to date. In concert, endothelial cell specific tyrosine kinase receptors, Tie 1, Tie 2 and Flt‐1 and Flk‐1 were also significantly enhanced in the preconditioned myocardium. The redox‐regulated transcription factor NFkB was found to play an essential role in the preconditioning regulation of angiogenesis

Keywords: ischemic preconditioning ‐ hypoxic preconditioning, angiogenesis, redox signaling, VEGF, NFκB

References

  • 1. Shizukuda Y., Iwamoto T., Mallet R.T., Downey H.F., Hypoxic preconditioning attenuates stunning caused by repeated coronary artery occlusions in dog heart, Cardiovasc. Res., 27: 559–564, 1993. [DOI] [PubMed] [Google Scholar]
  • 2. Lasley R.D., Anderson G.M., Mentzer R.M., Ischemic and hypoxic preconditioning enhance postischemic recovery of function in the rat heart, Cardiovasc. Res., 27: 565–570, 1993. [DOI] [PubMed] [Google Scholar]
  • 3. Zhai X., Lawson C.S., Cave A.C., Hearse D.J., Preconditioning and postischemic contractile dysfunction:the role of impaired oxygen delivery vs, extracellular metabolite accumulation, J. Mol. Cell. Cardiol., 25: 847–857, 1993. [DOI] [PubMed] [Google Scholar]
  • 4. Ashraf M., Suleiman J., Ahmad M., Ca2+ preconditioning elicits a unique protection against the Ca2+ paradox injury in rat heart, Circ. Res., 74: 360–367, 1994. [DOI] [PubMed] [Google Scholar]
  • 5. Thornton J.D., Liu G.S., Olsson R.A., Downey J.M., Intravenous pretreatment with A1‐selective adenosine analogues protects the heart against infarction, Circulation., 85: 659–665, 1992. [DOI] [PubMed] [Google Scholar]
  • 6. Banerjee A., Locke‐Winter C., Rogers K.B., Mitchell M.B., Brew E.C., Cairns C.B., Bensard D.D., Harken A.H., Preconditioning against myocardial dysfunction after ischemia and reperfusion by an A1‐adrenergic mechanism, Circ. Res., 73: 656–670, 1993. [DOI] [PubMed] [Google Scholar]
  • 7. Thornton J.D., Downey J.M., Pretreatment with pertussis toxin blocks the protective effects of preconditioning: evidence for a Gi‐protein mechanism, J. Mol. Cell. Cardiol., 25: 311–320, 1993. [DOI] [PubMed] [Google Scholar]
  • 8. Ovize M., Kloner R.A., Przyklenk K., Stretch preconditions canine myocardium, Am. J. Physiol., 266: H137–H146, 1994. [DOI] [PubMed] [Google Scholar]
  • 9. Neely J.R., Grotyohann L.W., Role of glycolytic products in damage to ischemic myocardium, Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts, Circ. Res., 55: 816–824, 1984. [DOI] [PubMed] [Google Scholar]
  • 10. Engelman D.T., Watanabe M., Engelman R.M., Rousou J.A., Kisin E., Kagan V.E., Maulik N., Das D.K., Hypoxic preconditioning preserves antioxidant reserve in the working rat heart, Cardiovas Res., 29: 133–140, 1995. [PubMed] [Google Scholar]
  • 11. Maulik N., Watanabe M., Zu Y‐L., Huang C–K., Cordis G.A., Schely J.A., Das D.K., Ischemic preconditioning triggers the activation of MAP kinases and MAPKAP kinase 2 in rat hearts, FEBS Lett., 396: 233–237, 396. [DOI] [PubMed] [Google Scholar]
  • 12. Maulik N., Yoshida T., Zu Y‐L., Sato M., Banerjee A, Das D.K., Ischemic preconditioning triggers tyrosine kinase signaling: a potential role for MAPKAP kinase 2, Am. J. Physiol., 275: H1857–H1864, 1998. [DOI] [PubMed] [Google Scholar]
  • 13. Maulik N., Sato M., Brenden D. P., Das D.K., An essenetial role of NF‐αB in tyrosine kinase signaling of p38 MAP kinase regulation of myocardial adaptation to ischemia, FEBS Lett., 429: 365–369, 1998. [DOI] [PubMed] [Google Scholar]
  • 14. Das D.K., Maulik N., Moraru I.I., Gene expression in acute myocardial stress, Induction by hypoxia, ischemia, reperfusion, hyperthermia and oxidative stress, J. Mol. Cell. Cardiol., 27: 181–193, 1995. [DOI] [PubMed] [Google Scholar]
  • 15. Maulik N., Watanabe M., You‐Li Zhu, Huang C.K., Cordis G.A., Schley J.A., Das D.K., FEBS Lett., 396: 233–237, 1996. [DOI] [PubMed] [Google Scholar]
  • 16. Liu T.N., Nian G.M., Chen S.E., Cheung W.M., Chang C., Lin W. C., Hsu C.Y., Induction of Tie‐1 and Tie‐2 receptor protein expression after cerebral ischemia‐reperfusion, J. Cereb. Blood Flow Metab., 21: 690–701, 2001. [DOI] [PubMed] [Google Scholar]
  • 17. Brand T., Sharma H.S., Fleischmann K.E., Duncker D.J., McFalls E.O., Verdue P.D., Schaper W., Proto‐oncogene expression in porcine myocardium subjected to ischemia and reperfusion, Circ. Res., 71: 1351–1360, 1992. [DOI] [PubMed] [Google Scholar]
  • 18. Ely S.W., Berne R.M., Protective effects of adenosine in myocardial ischemia, Circulation, 85: 893–904, 1992. [DOI] [PubMed] [Google Scholar]
  • 19. Fukuda S., Li Zhu, Engelman R.M., Das D.K., Maulik N., Ischemic preconditioning (PC) triggers myocardial angiogenesis by upregulating vascular endothelial growth factor (VEGF), Surgical Forum, LII: 65–67, 2001. [Google Scholar]
  • 20. Senger D.R., Connolly D.T., van de W. L, Feder J., Dvorak H.F., Purification and NH2‐terminal amino acid sequence of guinea pig tumor‐secreted vascular permeability factor, Cancer Res. 50: 1774–1778, 1990. [PubMed] [Google Scholar]
  • 21. Fong G‐H., Rossant J., Gerstenstein M., Breitman M.L., Role of the Flt‐1 receptor tyrosine kinase in regulating the assambly of vascular endothelium, Nature, 376: 66–70, 1995. [DOI] [PubMed] [Google Scholar]
  • 22. Takeshita S., Zheng L.P., Brogi E., Kearney M., Pu L.Q., Therapeutic angiogenesis, A single intra arterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model, J. Clin. Invest., 93: 662–670, 1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Asahara T., Chen D., Takahashi T., Fujikawa K., Kearney M., Magner M., Yancopoulos G. D., Isner J.M., Tie‐2 receptor ligands, angiopoietin‐1 and angiopoietin‐2, modulate VEGF‐induced postnatal neovascularization, Circ. Res., 83: 342–343, 1998. [DOI] [PubMed] [Google Scholar]
  • 24. Isner J.M., Pieczek A., Schainfed R., Blair R., Haley L., Asahara T., Rosenfield K., Razvi S., Walsh K., Symes J., Clinical evidence of angiogenesis is after arterial gene transfer of ph VEGF165 in patient with ischemic limb, Lancet, 348: 370–374, 1996. [DOI] [PubMed] [Google Scholar]
  • 25. Banai S., Jaklitsch M.T., Shou M., Lazarous D.F., Scheinowitz M., Biro S., Epstein S.E., Unger E.F., Angiogenic‐induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs, Circulation, 89: 2183–2189, 1994. [DOI] [PubMed] [Google Scholar]
  • 26. Pearlman J.D., Hibberd M.G., Chuang M.L., Harada K., Lopez J.J., Gladstone S.R., Friedman M., Sellke F.W., Simons M., Magnetic resonance mapping demonstrates benefits of VEGF‐induced myocardial angiogenesis, Nat. Med., 1: 1085–1089, 1995. [DOI] [PubMed] [Google Scholar]
  • 27. Maruyama K., Mori Y., Murasawa S., Masaki H., Takahashi N., Tsutusmi Y., Moriguchi Y., Shibazaki Y., Tanaka Y., Shibuya M., Inada M., Matsubara H., Iwasaka T., Interleukin‐1 beta upregulates cardiac expression of vascular endothelial growth factor and its receptor KDA/FLK‐1 via activation of protein tyrosine kinases, J. Mol. Cell. Cardiol., 31: 607–617, 1999. [DOI] [PubMed] [Google Scholar]
  • 28. Rousseau S., Houle F., Landry J., Hout J., p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells, Oncogene, 15: 2169–2177, 1997. [DOI] [PubMed] [Google Scholar]
  • 29. Tomanek R.J., Ratajska A., Kitten G.T., Yue X., Sandra A., Vascular endothelial growth factor expression coincides with coronary vasculogenesis and angiogenesis, Dev. Dyn., 215: 54–61, 1999. [DOI] [PubMed] [Google Scholar]
  • 30. Wong A.L., Haroon Z.A., Werner S., Dewhirst M.W., Greenberg C.S., Tie‐2 expression and phosphorylation in angiogenic and quiescent adult tissues Dev. Dyn., 81: 567–574, 1997. [DOI] [PubMed] [Google Scholar]
  • 31. Mustonen T., Alitalo K., Endothelial receptor tyrosine kinases involved in angiogenesis, J. Cell. Biol., 129: 895, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Sato T.N., Qin Y., Kozak C.A., Audus K.L., Tie‐1 and Tie‐2 define another class of putative receptor tyrosine kinase genes expressed in early embryonic vascular system, Proc. Natl. Acad. Sci. USA, 90: 9355–9358, 1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. Kaipainen A., Vlaykova T., Hatva E., Bohling T., Jekunen A., Pyrhonen S., Alitalo K., Enhanced expression of the Tie‐receptor tyrosine kinase mesenger RNA in the vascular endothelium of metastatic melanomas, Cancer Res., 54: 6571–6577, 1994. [PubMed] [Google Scholar]
  • 34. Schnurch H. and Risau W., Expression of Tie‐2, a member of a novel family of receptor tyrosine kinases, in the endothelial cell lineage, Development, 119: 957–968, 1993. [DOI] [PubMed] [Google Scholar]
  • 35. Ziegler S.F., Schneringer J.A., Schooley K.A., Baum P.R., Molecular cloning and characterization of a novel receptor protein tyrosine kinase from human placenta, Oncogene, 8: 663–670, 1993. [PubMed] [Google Scholar]
  • 36. Partanen J., Armstrong E., Makela T.P., Korhonen J., Sandberg M., Renkonen R., Knuutila S., Huebner K., Alitalo K., A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains, Mol. Cell. Biol., 12: 1698–1707, 1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. Takakura N., Huang X.L., Naruse T., Hamaguchi I., Dumont D.J., Yancopoulos G.D., Suda T., Critical role of the Tie‐2 endothelial cell receptor in the development of definitive hematopoiesis, Immunity, 9: 677, 1998. [DOI] [PubMed] [Google Scholar]
  • 38. Suri C., Jones P.F., Patan S., Bartunkova S., Maisonpierre P.C., Davis S., Sato T.N., Yancopoulos G.D., Cell, 87: 1153–1155, 1996. [DOI] [PubMed] [Google Scholar]
  • 39. 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., Isolation of angiopoietin‐1, a ligand for the Tie‐2 receptor, by secretion‐trap expression cloning, Cell, 87: 1161–1169, 1996. [DOI] [PubMed] [Google Scholar]
  • 40. Maisonpierre P., Suri C., Jones P., Bartunkova S., Wiegand S.J., Radziejewski C., Compton D., McClain J., Aldrich T.H., Papadopoulos N, Daly T.J., Davis S., Sato T., Yancopoulos G., Angiopoietin‐2, a natural antagonist for Tie‐2 that disrupts in vivo angiogenesis, Science, 277: 55–60, 1997. [DOI] [PubMed] [Google Scholar]
  • 41. Dumont D.J., Fong G.H., Puri M.C., Gradwohl G., Alitalo K., Breitman M.L., Vascularization of the mouse embryo: a study of Flk‐1, tek, tie, and vascular endothelial growth factor expression during development, Dev Dyn, 203: 80–92, 1995. [DOI] [PubMed] [Google Scholar]
  • 42. Meng X., Brown J.M., Ao L., Shames B.D., Banerjee A., Harken A.H., Reduction of infarct size in the rat heart by LPS preconditioning is associated with expression of angiogenic growth factors and increased capillary density, Shock, 12: 25–31, 1999. [DOI] [PubMed] [Google Scholar]
  • 43. Hashimoto E., Ogita T., Nakaoka T., Matsuoka R., Takao A., Kira Y., Rapid induction of vascular endothelial growth factor expression by transient ischemia in rat heart, Am. J. Physiol., 267: H1948–H1954, 1994. [DOI] [PubMed] [Google Scholar]
  • 44. Ladoux A., Frelin C., Hypoxia is a strong inducer of vascular endothelial growth factor mRNA expression in the heart, Biochem Biophys. Res. Commun. 195: 1005–1010, 1993. [DOI] [PubMed] [Google Scholar]
  • 45. Villaschi S., Nicosia R.F., Angiogenic role of endogenous basic fibroblast growth factor released by rat aorta after injury, Am. J. Pathol., 143: 181–190, 1993. [PMC free article] [PubMed] [Google Scholar]
  • 46. Kapadia S., Lee J., Torre‐Amione G., Birdsall H.H., Ma T.S., Mann D.L., Tumor necrosis factor‐α gene and protein expression in adult expression in adult feline myocardium after endotoxin administration, J. Clin. Invest. 96: 1042–1052, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47. Leibovich S.J., Polverini P.J., Shepard H.M., Wiseman D.M., Shively V., Nuseir N., Macrophage‐induced angiogenesis is mediated by tumor necrosis factor‐?, Nature, 329: 630–632, 1987. [DOI] [PubMed] [Google Scholar]
  • 48. Frater‐Schroder M., Risau W., Hallmann R, Gautschi P., Bohlen P., Tumor necrosis factor type a, α potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo , Proc. Natl. Acad. Sci. USA, 84: 5277–5281, 1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49. Yoshida S., Ono M., Shono T., Izumi H., Ishibashi T., Suzuki H., Kuwano M., Involvement of interleukin ‐8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha‐dependent angiogenesis, Mol. Cell. Biol., 4015–4023, 1997. [DOI] [PMC free article] [PubMed]
  • 50. Yanagisawa‐Miwa A., Uchida Y., Nakamura F., Tomaru T., Kido H., Kamijo T., Sugimoto T., Kaji K., Utsuyama M., Kurashima C., Ito H., Salvage of infarcted myocardium by angiogenic action of basic growth factor, Science, 257: 1401–1403, 1992. [DOI] [PubMed] [Google Scholar]
  • 51. Harada K., Friedman M., Lopez J.J., Wang S.Y., Li J., Prasad P.V., Pearlman J.D., Edelman E.R., Selke F. W, Simons M., Vascular endothelial growth factor administration in chronic myocardial ischemia, Am. J. Physiol., 270: H1791–H1802, 1996. [DOI] [PubMed] [Google Scholar]
  • 52. Pepper M.S., Ferrara N., Orci L., Montesano R., Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro , Biochem. Biophys. Res. Commun., 189: 824–831, 1992. [DOI] [PubMed] [Google Scholar]
  • 53. Lou Z., Diaco M., Murohara T., Ferrara N., Isner J.M., Symes J.F., Vascular endothelial growth factor attenuates myocardial ischemiareperfusion injury, Ann. Thorac. Surg., 64: 993–998, 1997. [DOI] [PubMed] [Google Scholar]
  • 54. Hudlicka O., Brown M., Egginton S., Angiogenesis in skeletal and cardiac muscle, Physiol. Rev., 72: 369–417, 1992. [DOI] [PubMed] [Google Scholar]
  • 55. DeVries C., Escobedo J.A., Veno H., Houck K., Ferrara N., Williams L.T., The fms‐like tyrosine kinase, a receptor for vascular endothelial growth factor, Science, 255: 989–991, 1992. [DOI] [PubMed] [Google Scholar]
  • 56. Millauer B., Shawver L.K., Plate K.H., Risau W., Ullrich A., Glioblastoma growth inhibited in vivo by a dominant negative Flk‐1 mutant, Nature, 367: 576–579, 1994. [DOI] [PubMed] [Google Scholar]
  • 57. Ladoux A., Frelin C., Hypoxia is a strong inducer of vascular endothelial growth factor mRNA expression in the heart, Biochem. Biophys. Res. Commun. 195: 1005–1010, 1993. [DOI] [PubMed] [Google Scholar]
  • 58. Minchenko A., Bauer T., Salceda S., Caro, Hypoxia stimulation of vascular endothelial growth factor expression in vitro and in vivo , J. Lab Invest, 71: 374–379, 1994. [PubMed] [Google Scholar]
  • 59. Kuo N., Benhayon D., Przybylski R.J., Martin R.J., LaManna J.C., Prolonged hypoxia increases vascular endothelial growth factor mRNA and protein in adult mouse brain, J. Appl. Physiol., 86: 260–264, 1999. [DOI] [PubMed] [Google Scholar]
  • 60. Tuder R.M., Voelkel N.F., Flook B.E., Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide, J. Clin. Invest., 95: 1798–1807, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61. Banai S., Shweiki D., Pinson A., Chandra M., Lazarovici G., Keshet E., Upregulation of vascular endothelial growth factor expression induced by myocardial ischemia: implications for coronary angiogenesis, Cardiovasc Res 28: 1176–1179, 1994. [DOI] [PubMed] [Google Scholar]
  • 62. Hashimoto E., Ogita T., Nakaoka T., Matsuoka R., Takao A., Kira Y., Rapid induction of vascular endothelial growth factor expression by transient ischemia in the rat heart, Am. J. Physiol., 267: H1948–H1954, 1994. [DOI] [PubMed] [Google Scholar]
  • 63. Li J., Brown L.F., Hibberd M.G., Grossman J.D., Morgan J.P., Simons M., VEGF, flk‐1, and flt‐1 expression in a rat myocardial infarction model of angiogenesis, Am. J. Physiol., 270: H1803–H1811, 1996. [DOI] [PubMed] [Google Scholar]
  • 64. Takagi H., King G.L., Ferrara N., Aiello L.P., Hypoxia regulates vascular endothelial growth factor receptor KDR/Flk gene expression through adenosine A2 receptors in retinal capillary endothelial cells, Invest. Ophthalmol. Vis. Sci., 37: 1311–1321, 1996. [PubMed] [Google Scholar]
  • 65. Brogi E., Schatteman G., Wu T., Kim E.A., Varticovski L., Keyt B., Isner J.M., Hypoxiainduced paracrine regulation of vascular endothelial growth factor receptor expression, J. Clin. Invest., 97: 469–476, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66. Ikeda E., Achen M.G., Breier G., Risau W., Hypoxia‐induced transcriptional activation and increased mRNA stability of vascular endothelial growth factor in C6 glioma cells, J. Biol. Chem., 270: 1961–1976, 1995. [DOI] [PubMed] [Google Scholar]
  • 67. Rastinejad F., Bouck N., Oncogenes and tumor suppressor genes in the regulation of angiogenesis In: Tumor Angiogenesis (Ferrara N., ed.), Oxford University Press, New York , pp. 101–110, 1997. [Google Scholar]
  • 68. Wood K.W., Sarnecki C., Roberts T.M., Blenis J., RAS mediates nerve growth factor receptor modulation of three signal transducing protein kinases: MAP kinases, Raf‐1, and RSK, Cell, 68: 1041–1050, 1992. [DOI] [PubMed] [Google Scholar]
  • 69. Pages G., Lenormand P., L'Allemain G., Chambard J‐C., Meloche S., Pouyssegur J., Mitogen‐activated protein kinases p42mapk and p44mapk are required for fibroblast proliferation, Proc. Natl. Acad. Sci. USA, 90: 8319–8322, 1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70. Seetharam L., Gotoh N., Maru Y., Neufeld G., Yamaguchi S., Shibuya M., A unique signal transduction from Flt‐tyrosine kinase, a receptor for vascular endothelial growth factor VEGF, Oncogene, 10: 135–147, 1995. [PubMed] [Google Scholar]
  • 71. Mandriota J., Pepper M.S., Regulation of Angiopoietin ‐2 mRNA levels in bovine microvascular endothelial cells by cytokines and hypoxia, Circ. Res., 83: 852–859, 1998. [DOI] [PubMed] [Google Scholar]
  • 72. Puceat M., Hilal‐Dandan R., Strulovici B., Brunton L., Heller Brown.J., Differential regulation of protein kinase C isoforms in isolated neonatal and adult rat crdiomyocytes, J. Biol. Chem., 271: 24962–24966, 1996. [PubMed] [Google Scholar]
  • 73. Johnson J.A., Gray M.O., Karliner J.S., Chen CH., Mochly‐Rosen D., An improved permeabilization protocol for the introduction of peptides into cardiac myocytes, Application to protein kinase C research, Circ. Res., 79: 1086–1099, 1996. [DOI] [PubMed] [Google Scholar]
  • 74. Maxwell P.H., Pugh C.W., Ratcliffe P.J., Inducible operation of the erythropoitin 3' enhancer in multiple cell lines: evidence for a widespread oxygen ‐sensing mechanism, Proc. Natl. Acad. Sci. USA, 90: 2423–2427, 1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 75. Bandyopadhyay R.S., Phelan M., Faller D.V., Hypoxia induces AP‐1 regulated genes and AP‐1 transcription factor binding in human endothelial and other cell types, Biochem. Biophys., 1264: 72–78, 1995. [DOI] [PubMed] [Google Scholar]
  • 76. Yao K.S., Xanthoudakis S., Curran T., O'Dwyer P.J., Involvement of NFB in the induction of NAD(P)H quinone oxidoreductase by hypoxia, oltipraz and mitomycin C, Biochem. Pharmacol., 49: 275–282, 1995. [DOI] [PubMed] [Google Scholar]
  • 77. Yoshida A., Yoshida S., Ishibashi T., Kuwano M., Inomata H., Suppression of retinal neovascularization by the NF‐B inhibitor pyrrolidine dithiocarbamate in mice, Invest. Ophthalmol. Vis. Sci., 40: 1624–1629, 1999. [PubMed] [Google Scholar]
  • 78. Lelkes P.I., Hahn K.L., Sukovich D.A., Karmiol. S. , Schmidt D.H., On the possible role of reactive oxygen species in angiogenesis, Adv. Exp. Med. Biol., 454: 295–310, 1998. [DOI] [PubMed] [Google Scholar]
  • 79. Yoshida A., Yoshida S., Khalil A.K., Ishibashi T., Inomata H., Role of NF‐B mediated interleukin‐8 expression in intraocular neovascularization, Invest. Ophthalmol. Vis. Sci., 39: 1097–1106, 1998. [PubMed] [Google Scholar]
  • 80. Smeal T., Angel P., Meek J., Karin M., Different requirements for formation of Jun‐Jun and Jun‐Fos complexes, Genes Dev., 3: 2091–2100, 1989. [DOI] [PubMed] [Google Scholar]
  • 81. Tischer E., Mitchell R., Hartman T., Silva M., Gospodarowicz D., Fiddes JC., Abraham JA., The human gene for vascular endothelial growth factor, Multiple protein forms are encoded through alternative exon slicing, J. Biol. Chem., 266: 11947–11954, 1991. [PubMed] [Google Scholar]
  • 82. Shweiki D., Itin A., Soffer D., Keshet E., Vascular endothelial growth factor induced by hypoxia may mediate hypoxia‐initiated angiogenesis, Nature, 359: 843–845, 1992. [DOI] [PubMed] [Google Scholar]
  • 83. Ryuto M., Ono M., Izumi H., Yoshida S., Weich H.A., Kohno K., Kuwano M., Induction of vascular endothelial growth factor by tumor necrosis factor α in human glioma cells, J. Biol. Chem., 271: 28220–28228, 1996. [DOI] [PubMed] [Google Scholar]
  • 84. Nor J.E., Christensen J., Mooney D.J., Polverini P.J., Vascular endothelial growth factor (VEGF)‐mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl‐2 expression, Am. J. Pathol., 154: 375–384, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 85. Sasaki H., Fukuda S., Otani H., Zhu Li, Engelman R.M., Das D.K., Maulik N., Hypoxic preconditioning triggers myocardial angiogenesis: a novel approach to enhance contractile functional reserve in rat with myocardial infarction, J. Mol. Cell. Cardiol., (In Press), 2002. [DOI] [PubMed]
  • 86. Gerber H‐P., McMurtrey A., Kowalski J., Yan M., Keyt B.A., Dixit V., Ferrara N., Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'‐ kinase/AKT signal transduction pathway, J. Biol. Chem., 273: 30336–30343, 1998. [DOI] [PubMed] [Google Scholar]
  • 87. Papapetropoulos A., Fulton D., Mahboubi K., Kalb R.G., O'Connor D.S., Li F., Altieri D.C., Sessa W.C., Angiopoietin‐1 inhibits endothelial cell apoptosis via the AKT/survivin pathway, J. Biol. Chem., 275: 9102–9105, 2000. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Cellular and Molecular Medicine are provided here courtesy of Blackwell Publishing

RESOURCES