The role of hypoxia in vascular injury and repair

Annual Review of Pathology: Mechanisms of Disease

Volumn 3, Issue , 2008, Pages 615-643

  Walshe, Tony E ^a   D'Amore, Patricia A ^a  

^a SCHEPENS EYE RESEARCH INSTITUTE   (United States)

Author keywords

Angiogenesis; Conditioning; Erythropoiesis; Hypoxia inducible factor; Ischemia; Reperfusion

Indexed keywords

ERYTHROPOIETIN; HYPOXIA INDUCIBLE FACTOR 1; TRANSCRIPTION FACTOR; VASCULOTROPIN;

ACUTE DISEASE; BLOOD VESSEL INJURY; CELL DEATH; CHRONIC DISEASE; EYE DISEASE; GENE EXPRESSION; HEART MUSCLE ISCHEMIA; HUMAN; HYPOXEMIA; HYPOXIA; INFLAMMATION; ISCHEMIA; NONHUMAN; NUTRIENT SUPPLY; PATHOGENESIS; PRIORITY JOURNAL; REPERFUSION INJURY; REVIEW; TISSUE PERFUSION; TISSUE REPAIR; TUMOR GROWTH;

ANIMALS; ANOXIA; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CELLS, CULTURED; DISEASE MODELS, ANIMAL; ERYTHROPOIESIS; GENE EXPRESSION REGULATION; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1; MICE; NEOVASCULARIZATION, PHYSIOLOGIC; RECOVERY OF FUNCTION; REPERFUSION; REPERFUSION INJURY;

EID: 41749083716     PISSN: 15534006     EISSN: 15534014     Source Type: Book Series    
DOI: 10.1146/annurev.pathmechdis.3.121806.151501     Document Type: Review

References (152)

1. Braun RD, Lanzen JL, Snyder SA, Dewhirst MW. 2001. Comparison of tumor and normal tissue oxygen tension measurements using OxyLite or microelectrodes in rodents. Am. J. Physiol. Heart Circ. Physiol. 280:H2533-44
2. Ryan JM, Leonardi GP, Gordon AS. 1983. Renal and extrarenal production of erythropoietin following exchange transfusion with plasma or a perfluorocarbon-polyol. Exp. Hematol. 11:891-98
3. Mu D, Chang YS, Vexler ZS, Ferriero DM. 2005. Hypoxia-inducible factor 1α and erythropoietin upregulation with deferoxamine salvage after neonatal stroke. Exp. Neurol. 195:407-15
4. Prass K, Scharff A, Ruscher K, Lowl D, Muselmann C, et al. 2003. Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin. Stroke 34:1981-86
5. Althaus J, Bernaudin M, Petit E, Toutain J, Touzani O, Rami A. 2006. Expression of the gene encoding the proapoptotic BNIP3 protein and stimulation of hypoxia-inducible factor-1α (HIF-1α) protein following focal cerebral ischemia in rats. Neurochem. Int. 48:687-95
6. Maynard MA, Evans AJ, Hosomi T, Hara S, Jewett MA, Ohh M. 2005. Human HIF-3α4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinoma. FASEB J 19:1396-406
7. Heidbreder M, Frohlich F, Johren O, Dendorfer A, Qadri F, Dominiak P. 2003. Hypoxia rapidly activates HIF-3α mRNA expression. FASEB J. 17:1541-43
8. Ding K, Scortegagna M, Seaman R, Birch DG, Garcia JA. 2005. Retinal disease in mice lacking hypoxia-inducible transcription factor-2α. Invest. Ophthalmol. Vis. Sci. 46:1010-16
9. Gordeuk VR, Sergueeva AI, Miasnikova GY, Okhotin D, Voloshin Y, et al. 2004. Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors. Blood 103:3924-32
10. Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, et al. 2001. Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292:468-72
11. Bruick RK, McKnight SL. 2001. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294:1337-40
12. Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, et al. 2001. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107:43-54
13. Nakayama K, Frew IJ, Hagensen M, Skals M, Habelhah H, et al. 2004. Siah2 regulates stability of prolyl-hydroxylases, controls HIF1α abundance, and modulates physiological responses to hypoxia. Cell 117:941-52
14. Jeong JW, Bae MK, Ahn MY, Kim SH, Sohn TK, et al. 2002. Regulation and destabilization of HIF-1α by ARD1-mediated acetylation. Cell 111:709-20
15. Chang CC, Lin MT, Lin BR, Jeng YM, Chen ST, et al. 2006. Effect of connective tissue growth factor on hypoxia-inducible factor 1α degradation and tumor angiogenesis. J. Natl. Cancer Inst. 98:984-95
16. Bilton R, Mazure N, Trottier E, Hattab M, Dery MA, et al. 2005. Arrest-defective-1 protein, an acetyltransferase, does not alter stability of hypoxia-inducible factor (HIF)-1α and is not induced by hypoxia or HIF. J. Biol. Chem. 280:31132-40
17. Makino Y, Kanopka A, Wilson WJ, Tanaka H, Poellinger L. 2002. Inhibitory PAS domain protein (IPAS) is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3α locus. J. Biol. Chem. 277:32405-8
18. Makino Y, Cao R, Svensson K, Bertilsson G, Asman M, et al. 2001. Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Nature 414:550-54
19. Schluter KD, Jakob G, Ruiz-Meana M, Garcia-Dorado D, Piper HM. 1996. Protection of reoxygenated cardiomyocytes against osmotic fragility by nitric oxide donors. Am. J. Physiol. Heart Circ. Physiol. 271:H428-34
20. Chang TC, Huang CJ, Tam K, Chen SF, Tan KT, et al. 2005. Stabilization of hypoxia-inducible factor-1α by prostacyclin under prolonged hypoxia via reducing reactive oxygen species level in endothelial cells. J. Biol. Chem. 280:36567-74
21. -/- mice. Nat. Genet. 35:331-40
22. Oktay Y, Dioum E, Matsuzaki S, Ding K, Yan LJ, et al. 2007. Hypoxia inducible factor 2α regulates expression of the mitochondrial aconitase chaperone protein frataxin. J. Biol. Chem. 282:11750-56
23. El-Remessy AB, Al-Shabrawey M, Platt DH, Bartoli M, Behzadian MA, et al. 2007. Peroxynitrite mediates VEGF's angiogenic signal and function via a nitration-independent mechanism in endothelial cells. FASEB J. 21:2528-39
24. Whitlock NA, Agarwal N, Ma JX, Crosson CE. 2005. Hsp27 upregulation by HIF-1 signaling offers protection against retinal ischemia in rats. Invest. Ophthalmol. Vis. Sci. 46:1092-98
25. Zhou J, Schmid T, Frank R, Brune B. 2004. PI3K/Akt is required for heat shock proteins to protect hypoxia-inducible factor 1α from pVHL-independent degradation. J. Biol. Chem. 279:13506-13
26. Mestril R, Chi SH, Sayen MR, O'Reilly K, Dillmann WH. 1994. Expression of inducible stress protein 70 in rat heart myogenic cells confers protection against simulated ischemia-induced injury. J. Clin. Invest. 93:759-67
27. Dachs GU, Patterson AV, Firth JD, Ratcliffe PJ, Townsend KM, et al. 1997. Targeting gene expression to hypoxic tumor cells. Nat. Med. 3:515-20
28. Serganova I, Doubrovin M, Vider J, Ponomarev V, Soghomonyan S, et al. 2004. Molecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice. Cancer Res. 64:6101-8
29. Talks KL, Turley H, Gatter KC, Maxwell PH, Pugh CW, et al. 2000. The expression and distribution of the hypoxia-inducible factors HIF-1α and HIF-2α in normal human tissues, cancers, and tumor-associated macrophages. Am. J. Pathol. 157:411-21
30. Beasley NJ, Leek R, Alam M, Turley H, Cox GJ, et al. 2002. Hypoxia-inducible factors HIF-1α and HIF-2α in head and neck cancer: relationship to tumor biology and treatment outcome in surgically resected patients. Cancer Res. 62:2493-97
31. Teicher BA. 1995. Physiologic mechanisms of therapeutic resistance. Blood flow and hypoxia. Hematol. Oncol. Clin. N. Am. 9:475-506
32. Rofstad EK, Galappathi K, Mathiesen B, Ruud EB. 2007. Fluctuating and diffusion-limited hypoxia in hypoxia-induced metastasis. Clin. Cancer Res. 13:1971-78
33. Sowter HM, Ratcliffe PJ, Watson P, Greenberg AH, Harris AL. 2001. HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Res. 61:6669-73
34. Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, et al. 2004. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 6:553-63
35. Singh Jaggi J, Henke E, Seshan SV, Kappel BJ, Chattopadhyay D, et al. 2007. Selective α-particle mediated depletion of tumor vasculature with vascular normalization. PLoS ONE 2:e267
36. Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, et al. 2004. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat. Med. 10:145-47
37. Fukumura D, Jain RK. 2007. Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization. Microvasc. Res. In press
38. Villanueva A, Garcia C, Paules AB, Vicente M, Megias M, et al. 1998. Disruption of the antiproliferative TGF-β signaling pathways in human pancreatic cancer cells. Oncogene 17:1969-78
39. Lehmann K, Janda E, Pierreux CE, Rytomaa M, Schulze A, et al. 2000. Raf induces TGFβ production while blocking its apoptotic but not invasive responses: a mechanism leading to increased malignancy in epithelial cells. Genes Dev. 14:2610-22
40. Thomas DA, Massague J. 2005. TGF-β directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell 8:369-80
41. Chen YF, Feng JA, Li P, Xing D, Zhang Y, et al. 2006. Dominant negative mutation of the TGF-β receptor blocks hypoxia-induced pulmonary vascular remodeling. J. Appl. Physiol. 100:564-71
42. Orlidge A, D'Amore PA. 1987. Inhibition of capillary endothelial cell growth by pericytes and smooth muscle cells. J. Cell Biol. 105:1455-62
43. Sato Y, Rifkin DB. 1989. Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-β 1-like molecule by plasmin during coculture. J. Cell Biol. 109:309-15
44. Hirschi KK, Rohovsky SA, D'Amore PA. 1998. PDGF, TGF-β, and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate J. Cell Biol. 141:805-14
45. Darland DC, Massingham LJ, Smith SR, Piek E, Saint-Geniez M, D'Amore PA. 2003. Pericyte production of cell-associated VEGF is differentiation-dependent and is associated with endothelial survival. Dev. Biol. 264:275-88
46. Sanchez-Eisner T, Botella LM, Velasco B, Corbi A, Attisano L, Bernabeu C. 2001. Synergistic cooperation between hypoxia and transforming growth factor-β pathways on human vascular endothelial growth factor gene expression. J. Biol. Chem. 276:38527-35
47. Sanchez-Eisner T, Botella LM, Velasco B, Langa C, Bernabeu C. 2002. Endoglin expression is regulated by transcriptional cooperation between the hypoxia and transforming growth factor-β pathways. J. Biol. Chem. 277:43799-808
48. Bernhardt WM, Wiesener MS, Weidemann A, Schmitt R, Weichert W, et al. 2007. Involvement of hypoxia-inducible transcription factors in polycystic kidney disease. Am. J. Pathol. 170:830-42
49. Düwel A, Eleno N, Jerkic M, Arevalo M, Bolaños JP, et al. 2007. Reduced tumor growth and angiogenesis in endoglin-haploinsufficient mice. Tumour Biol. 28:1-8
50. Li C, Guo B, Wilson PB, Stewart A, Byrne G, et al. 2000. Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer. Int. J. Cancer 89:122-26
51. Lee SH, Mizutani N, Mizutani M, Luo Y, Zhou H, et al. 2006. Endoglin (CD105) is a target for an oral DNA vaccine against breast cancer. Cancer Immunol. Immunother. 55:1565-74
52. Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, et al. 1999. Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases. Cancer Res. 59:5830-35
53. Bos R, Zhong H, Hanrahan CF, Mommers EC, Semenza GL, et al. 2001. Levels of hypoxia-inducible factor-1 α during breast carcinogenesis. J. Natl. Cancer Inst. 93:309-14
54. Ryan HE, Lo J, Johnson RS. 1998. HIF-1α is required for solid tumor formation and embryonic vascularization. EMBO J. 17:3005-15
55. Jung CR, Hwang KS, Yoo J, Cho WK, Kim JM, et al. 2006. E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis. Nat. Med. 12:809-16
56. Krieg M, Haas R, Brauch H, Acker T, Flamme I, Plate KH. 2000. Up-regulation of hypoxia-inducible factors HIF-1α and HIF-2α under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function. Oncogene 19:5435-43
57. Calzada MJ, Esteban MA, Feijoo-Cuaresma M, Castellanos MC, Naranjo-Suárez S, et al. 2006. von Hippel-Lindau tumor suppressor protein regulates the assembly of intercellular junctions in renal cancer cells through hypoxia-inducible factor-independent mechanisms. Cancer Res. 66:1553-60
58. Krishnamachary B, Zagzag D, Nagasawa H, Rainey K, Okuyama H, et al. 2006. Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor-null renal cell carcinoma mediated by TCF3, ZFHX1A, and ZFHX1B. Cancer Res. 66:2725-31
59. Ohh M, Yauch RL, Lonergan KM, Whaley JM, Stemmer-Rachamimov AO, et al. 1998. The von Hippel-Lindau tumor suppressor protein is required for proper assembly of an extracellular fibroneetin matrix. Mol. Cell 1:959-68
60. Grosfeld A, Stolze IP, Cockman ME, Pugh CW, Edelmann M, et al. 2007. Interaction of hydroxylated collagen IV with the von Hippel-Lindau tumor suppressor. J. Biol. Chem. 282:13264-69
61. Moeller BJ, Cao Y, Li CY, Dewhirst MW. 2004. Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules. Cancer Cell 5:429-41
62. Martinive P, Defresne F, Bouzin C, Saliez J, Lair F, et al. 2006. Preconditioning of the tumor vasculature and tumor cells by intermittent hypoxia: implications for anticancer therapies. Cancer Res. 66:11736-44
63. Tang N, Wang L, Esko J, Giordano FJ, Huang Y, et al. 2004. Loss of HIF-1α in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis. Cancer Cell 6:485-95
64. Blouw B, Song H, Tihan T, Bosze J, Ferrara N, et al. 2003. The hypoxic response of tumors is dependent on their microenvironment. Cancer Cell 4:133-46
65. Moeller BJ, Dreher MR, Rabbani ZN, Schroeder T, Cao Y, et al. 2005. Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity. Cancer Cell 8:99-110
66. Galvez AS, Brunskill EW, Marreez Y, Benner BJ, Regula KM, et al. 2006. Distinct pathways regulate proapoptotic Nix and BNip3 in cardiac stress. J. Biol. Chem. 281:1442-48
67. Fei P, Wang W, Kim SH, Wang S, Burns TF, et al. 2004. Bnip3L is induced by p53 under hypoxia, and its knockdown promotes tumor growth. Cancer Cell 6:597-609
68. Kamat CD, Green DE, Warnke L, Thorpe JE, Ceriello A, Ihnat MA. 2006. Mutant p53 facilitates proangiogenic, hyperproliferative phenotype in response to chronic relative hypoxia. Cancer Lett. 249:209-19
69. Roe JS, Kim H, Lee SM, Kim ST, Cho EJ, Youn HD. 2006. p53 stabilization and transactivation by a von Hippel-Lindau protein. Mol. Cell 22:395-405
70. Bruick RK. 2000. Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc. Natl. Acad. Sci. USA 97:9082-87
71. Carmeliet P, Dor Y, Herbert JM, Fukumura D, Brusselmans K, et al. 1998. Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394:485-90
72. Covello KL, Simon MC, Keith B. 2005. Targeted replacement of hypoxia-inducible factor-1α by a hypoxia-inducible factor-2α knock-in allele promotes tumor growth. Cancer Res. 65:2277-86
73. Onita T, Ji PG, Xuan JW, Sakai H, Kanetake H, et al. 2002. Hypoxia-induced, perinecrotic expression of endothelial Per-ARNT-Sim domain protein-1/hypoxia-inducible factor-2α correlates with tumor progression, vascularization, and focal macrophage infiltration in bladder cancer. Clin. Cancer Res. 8:471-80
74. Giatromanolaki A, Sivridis E, Fiska A, Koukourakis MI. 2006. Hypoxia-inducible factor-2α (HIF-2α) induces angiogenesis in breast carcinomas. Appl. Immunohistochem. Mol. Morphol. 14:78-82
75. Acs G, Zhang PJ, McGrath CM, Acs P, McBroom J, et al. 2003. Hypoxia-inducible erythropoietin signaling in squamous dysplasia and squamous cell carcinoma of the uterine cervix and its potential role in cervical carcinogenesis and tumor progression. Am. J. Pathol. 162:1789-806
76. Acs G, Xu X, Chu C, Acs P, Verma A. 2004. Prognostic significance of erythropoietin expression in human endometrial carcinoma. Cancer 100:2376-86
77. Gong K, Zhang N, Zhang Z, Na Y. 2006. Coexpression of erythopoietin and erythopoietin receptor in sporadic clear cell renal cell carcinoma. Cancer Biol. Ther. 5:582-85
78. Acs G, Zhang PJ, Rebbeck TR, Acs P, Verma A. 2002. Immunohistochemical expression of erythropoietin and erythropoietin receptor in breast carcinoma. Cancer 95:969-81
79. Tendler DS, Bao C, Wang T, Huang EL, Ratovitski EA, et al. 2001. Intersection of interferon and hypoxia signal transduction pathways in nitric oxide-induced tumor apoptosis. Cancer Res. 61:3682-88
80. Burke B, Tang N, Corke KP, Tazzyman D, Ameri K, et al. 2002. Expression of HIF-1α by human macrophages: implications for the use of macrophages in hypoxia-regulated cancer gene therapy. J. Pathol. 196:204-12
81. Leek RD, Talks KL, Pezzella F, Turley H, Campo L, et al. 2002. Relation of hypoxia-inducible factor-2α (HIF-2α) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in human breast cancer. Cancer Res. 62:1326-29
82. Grimshaw MJ, Balkwill FR. 2001. Inhibition of monocyte and macrophage chemotaxis by hypoxia and inflammation: a potential mechanism. Eur. J. Immunol. 31:480-89
83. Schmeisser A, Marquetant R, Illmer T, Graffy C, Garlichs CD, et al. 2005. The expression of macrophage migration inhibitory factor 1α (MIF 1α) in human atherosclerotic plaques is induced by different proatherogenic stimuli and associated with plaque instability. Atherosclerosis 178:83-94
84. Compeau CG, Ma J, DeCampos KN, Waddell TK, Brisseau GF, et al. 1994. In situ ischemia and hypoxia enhance alveolar macrophage tissue factor expression. Am. J. Respir. Cell Mol. Biol. 11:446-55
85. Kojima H, Sitkovsky MV, Cascalho M. 2003. HIF-1α deficiency perturbs T and B cell functions. Curr. Pharm. Des. 9:1827-32
86. Hellstrom I, Hellstrom KE, Pierce GE, Yang JP. 1968. Cellular and humoral immunity to different types of human neoplasms. Nature 220:1352-54
87. Ohta A, Sitkovsky M. 2001. Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature 414:916-20
88. Thanyasiri P, Celermajer DS, Adams MR. 2005. Endothelial dysfunction occurs in peripheral circulation patients with acute and stable coronary artery disease. Am. J. Physiol. Heart Circ. Physiol. 289:H513-17
89. Kang PM, Haunstetter A, Aoki H, Usheva A, Izumo S. 2000. Apoptosis during hypoxia and reoxygenation: morphological and molecular characterization of adult cardiomyocyte. Circ. Res. 87:118-25
90. Meyrick B, Reid L. 1980. Hypoxia-induced structural changes in the media and adventitia of the rat hilar pulmonary artery and their regression. Am. J. Pathol. 100:151-78
91. Salvaterra CG, Goldman WF. 1993. Acute hypoxia increases cytosolic calcium in cultured pulmonary arterial myocytes. Am. J. Physiol. Lung Cell Mol. Physiol. 264:L323-28
92. Hool LC. 2000. Hypoxia increases the sensitivity of the L-type Ca(2+) current to β-adrenergic receptor stimulation via a C2 region-containing protein kinase C isoform. Circ. Res. 87:1164-71
93. Chen SJ, Bradley ME, Lee TC. 1998. Chemical hypoxia triggers apoptosis of cultured neonatal rat cardiac myocytes: modulation by calcium-regulated proteases and protein kinases. Mol. Cell Biochem. 178:141-49
94. Meynier A, Razik H, Cordelet C, Gregoire S, Demaison L. 2003. Involvement of oxygen free radicals in the respiratory uncoupling induced by free calcium and ADP-magnesium in isolated cardiac mitochondria: comparing reoxygenation in cultured cardiomyocytes. Mol. Cell Biochem. 243:55-64
95. +-independent PLA2 in hypoxic ventricular myocytes. Am. J. Physiol. Cell Physiol. 274:C1727-37
96. Frank JS, Beydler S, Kreman M, Rau EE. 1980. Structure of the freeze-fractured sarcolemma in the normal and anoxic rabbit myocardium. Circ. Res. 47:131-43
97. + activities under hypoxia, acidosis, and no glucose in dog hearts. Am. J. Physiol. Heart Circ. Physiol. 249:H1078-85
98. Sano M, Minamino T, Toko H, Miyauchi H, Orimo M, et al. 2007. p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload. Nature 446:444-48
99. Johnson TM, Hammond EM, Giaccia A, Attardi LD. 2005. The p53QS transactivation-deficient mutant shows stress-specific apoptotic activity and induces embryonic lethality. Nat. Genet. 37:145-52
100. Toth A, Jeffers JR, Nickson P, Min JY, Morgan JP, et al. 2006. Targeted deletion of Puma attenuates cardiomyocyte death and improves cardiac function during ischemia-reperfusion. Am. J. Physiol. Heart Circ. Physiol. 291:H52-60
101. Webster KA, Discher DJ, Kaiser S, Hernandez O, Sato B, Bishopric NH. 1999. Hypoxia-activated apoptosis of cardiac myocytes requires reoxygenation or a pH shift and is independent of p53. J. Clin. Invest. 104:239-52
102. Graham RM, Frazier DP, Thompson JW, Haliko S, Li H, et al. 2004. A unique pathway of cardiac myocyte death caused by hypoxia-acidosis. J. Exp. Biol. 207:3189-200
103. Kirshenbaum LA, Singal PK. 1992. Changes in antioxidant enzymes in isolated cardiac myocytes subjected to hypoxia-reoxygenation. Lab. Invest. 67:796-803
104. Kokura S, Wolf RE, Yoshikawa T, Granger DN, Aw TY. 2000. T-lymphocyte-derived tumor necrosis factor exacerbates anoxia-reoxygenation- induced neutrophil-endothelial cell adhesion. Circ. Res. 86:205-13
105. Vanden Hoek T, Becker LB, Shao ZH, Li CQ, Schumacker PT. 2000. Preconditioning in cardiomyocytes protects by attenuating oxidant stress at reperfusion. Circ. Res. 86:541-48
106. Vanden Hoek TL, Becker LB, Shao Z, Li C, Schumacker PT. 1998. Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes. J. Biol. Chem. 273:18092-98
107. Calvillo L, Latini R, Kajstura J, Leri A, Anversa P, et al. 2003. Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc. Natl. Acad. Sci. USA 100:4802-6
108. Sharples EJ, Patel N, Brown P, Stewart K, Mota-Philipe H, et al. 2004. Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion. J. Am. Soc. Nephrol. 15:2115-24
109. Chong ZZ, Maiese K. 2007. Erythropoietin involves the phosphatidylinositol 3-kinase pathway, 14-3-3 protein and FOXO3a nuclear trafficking to preserve endothelial cell integrity. Br. J. Pharmacol. 150:839-50
110. Cai Z, Manalo DJ, Wei G, Rodriguez ER, Fox-Talbot K, et al. 2003. Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injury. Circulation 108:79-85
111. Warnecke C, Zaborowska Z, Kurreck J, Erdmann VA, Frei U, et al. 2004. Differentiating the functional role of hypoxia-inducible factor (HIF)-1α and HIF-2α (EPAS-1) by the use of RNA interference: erythropoietin is a HIF-2α target gene in Hep3B and Kelly cells. FASEB J 18:1462-64
112. Scortegagna M, Morris MA, Oktay Y, Bennett M, Garcia JA. 2003. The HIF family member EPAS1/HIF-2α is required for normal hematopoiesis in mice. Blood 102:1634-40
113. Scortegagna M, Ding K, Zhang Q, Oktay Y, Bennett MJ, et al. 2005. HIF-2α regulates murine hematopoietic development in an erythropoietin-dependent manner. Blood 105:3133-40
114. Morita M, Ohneda O, Yamashita T, Takahashi S, Suzuki N, et al. 2003. HLF/HIF-2α is a key factor in retinopathy of prematurity in association with erythropoietin. EMBO J. 22:1134-46
115. Garhofer G, Huemer KH, Zawinka C, Schmetterer L, Dorner GT. 2002. Influence of diffuse luminance flicker on choroidal and optic nerve head blood flow. Curr. Eye Res. 24:109-13
116. Garhofer G, Resch H, Weigert G, Lung S, Simader C, Schmetterer L. 2005. Short-term increase of intraocular pressure does not alter the response of retinal and optic nerve head blood flow to flicker stimulation. Invest. Ophthalmol. Vis. Sci. 46:1721-25
117. Jean-Louis S, Lovasik JV, Kergoat H. 2005. Systemic hyperoxia and retinal vasomotor responses. Invest. Ophthalmol. Vis. Sci. 46:1714-20
118. Cai J, Boulton M. 2002. The pathogenesis of diabetic retinopathy: old concepts and new questions. Eye 16:242-60
119. Ibrahim MA, Kanzaki T, Yamagata SI, Satoh N, Ueda S. 2005. Effect of diabetes on aortic nitric oxide synthesis in spontaneously hypertensive rats; does captopril modulate this effect? Life Sci. 77:1003-14
120. Connell P, Walshe T, Ferguson G, Gao W, O'Brien C, Cahill PA. 2007. Elevated glucose attenuates agonist- and flow-stimulated endothelial nitric oxide synthase activity in microvascular retinal endothelial cells. Endothelium 14:17-24
121. Riva CE, Logean E, Falsini B. 2004. Temporal dynamics and magnitude of the blood flow response at the optic disk in normal subjects during functional retinal flicker-stimulation. Neurosci. Lett. 356:75-78
122. Patel V, Rassam SM, Chen HC, Kohner EM. 1994. Oxygen reactivity in diabetes mellitus: effect of hypertension and hyperglycaemia. Clin. Sci. 86:689-95
123. Rassam SM, Patel V, Kohner EM. 1995. The effect of experimental hypertension on retinal vascular autoregulation in humans: a mechanism for the progression of diabetic retinopathy. Exp. Physiol. 80:53-68
124. Grunwald JE, Riva CE, Petrig BL, Sinclair SH, Brucker AJ. 1984. Effect of pure O2-breathing on retinal blood flow in normals and in patients with background diabetic retinopathy. Curr. Eye Res. 3:239-41
125. Evans DW, Harris A, Danis RP, Arend O, Martin BJ. 1997. Altered retrobulbar vascular reactivity in early diabetic retinopathy. Br. J. Ophthalmol. 81:279-82
126. Ben-Nun J, Alder VA, Constable IJ, Roberts CE. 1990. The patency of the retinal vasculature to erythrocytes in retinal vascular disease. Invest. Ophthalmol. Vis. Sci. 31:464-70
127. Le Devehat C, Khodabandehlou T, Vimeux M. 1994. Relationship between hemorheological and microcirculatory abnormalities in diabetes mellitus. Diabete Metab. 20:401-4
128. Behzadian MA, Wang XL, Al-Shabrawey M, Caldwell RB. 1998. Effects of hypoxia on glial cell expression of angiogenesis-regulating factors VEGF and TGF-β. Glia 24:216-25
129. Spranger J, Meyer-Schwickerath R, Klein M, Schatz H, Pfeiffer A. 1999. Deficient activation and different expression of transforming growdi factor-β isoforms in active proliferative diabetic retinopathy and neovascular eye disease. Exp. Clin. Endocrinol. Diab. 107:21-28
130. Pfeiffer A, Spranger J, Meyer-Schwickerath R, Schatz H. 1997. Growth factor alterations in advanced diabetic retinopathy: a possible role of blood retina barrier breakdown. Diabetes 46(Suppl. 2):S26-30
131. Cogan DG, Toussaint D, Kuwabara T. 1961. Retinal vascular patterns. IV. Diabetic retinopathy. Arch. Ophthalmol. 66:366-78
132. Gao W, Ferguson G, Connell P, Walshe T, Murphy R, et al. 2007. High glucose concentrations alter hypoxia-induced control of vascular smooth muscle cell growth via a HIF-1α-dependent pathway. J. Mol. Cell Cardiol. 42:609-19
133. Hammes HP, Lin J, Renner O, Shani M, Lundqvist A, et al. 2002. Pericytes and the pathogenesis of diabetic retinopathy. Diabetes 51:3107-12
134. Linsenmeier RA, Braun RD, McRipley MA, Padnick LB, Ahmed J, et al. 1998. Retinal hypoxia in long-term diabetic cats. Invest. Ophthalmol. Vis. Sci. 39:1647-57
135. Kondo T, Vicent D, Suzuma K, Yanagisawa M, King GL, et al. 2003. Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization. J. Clin. Invest. 111:1835-42
136. Ruberte J, Ayuso E, Navarro M, Carretero A, Nacher V, et al. 2004. Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye disease. J. Clin. Invest. 113:1149-57
137. Takagi H, Koyama S, Seike H, Oh H, Otani A, et al. 2003. Potential role of the angiopoietin/tie2 system in ischemia-induced retinal neovascularization. Invest. Ophthalmol. Vis. Sci. 44:393-402
138. Spranger J, Osterhoff M, Reimann M, Mohlig M, Ristow M, et al. 2001. Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. Diabetes 50:2641-45
139. Zhang SX, Wang JJ, Gao G, Parke K, Ma JX. 2006. Pigment epithelium-derived factor downregulates vascular endothelial growth factor (VEGF) expression and inhibits VEGF-VEGF receptor 2 binding in diabetic retinopathy. J. Mol. Endocrinol. 37:1-12
140. Pe'er J, Folberg R, Itin A, Gnessin H, Hemo I, Keshet E. 1996. Upregulated expression of vascular endothelial growth factor in proliferative diabetic retinopathy. Br. J. Ophthalmol. 80:241-45
141. Takagi H, King GL, Aiello LP. 1996. Identification and characterization of vascular endothelial growth factor receptor (Flt) in bovine retinal pericytes. Diabetes 45:1016-23
142. Okamoto N, Nishimura Y, Goami K, Harino S. 1998. Effect of hyperbaric oxygen on ophthalmic artery blood velocity in patients with diabetic neuropathy. Jpn. J. Ophthalmol. 42:406-10
143. Takano M, Meneshian A, Sheikh E, Yamakawa Y, Wilkins KB, et al. 2002. Rapid upregulation of endothelial P-selectin expression via reactive oxygen species generation. Am. J. Physiol. Heart Circ. Physiol. 283:H2054-61
144. Mansfield KD, Guzy RD, Pan Y, Young RM, Cash TP, et al. 2005. Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-α activation. Cell Metab. 1:393-99
145. Brunelle JK, Bell EL, Quesada NM, Vercauteren K, Tiranti V, et al. 2005. Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation. Cell Metab. 1:409-14
146. Zhang H, Agardh E, Agardh CD. 1991. Hydrogen peroxide production in ischaemic retina: influence of hyperglycaemia and postischaemic oxygen tension. Diabetes Res. 16:29-35
147. Lu M, Kuroki M, Amano S, Tolentino M, Keough K, et al. 1998. Advanced glycation end products increase retinal vascular endothelial growth factor expression. J. Clin. Invest. 101:1219-24
148. de Gooyer TE, Stevenson KA, Humphries P, Simpson DA, Gardiner TA, Stitt AW. 2006. Retinopathy is reduced during experimental diabetes in a mouse model of outer retinal degeneration. Invest. Ophthalmol. Vis. Sci. 47:5561-68
149. Drasdo N, Chiti Z, Owens DR, North RV. 2002. Effect of darkness on inner retinal hypoxia in diabetes. Lancet 359:2251-53
150. Dore-Duffy P, Balabanov R, Beaumont T, Katar M. 2005. The CNS pericyte response to low oxygen: early synthesis of cyclopentenone prostaglandins of the J-series. Microvasc. Res. 69:79-88
151. Catrina SB, Okamoto K, Pereira T, Brismar K, Poellinger L. 2004. Hyperglycemia regulates hypoxia-inducible factor-1α protein stability and function. Diabetes 53:3226-32
152. Fadini GP, Sartore S, Schiavon M, Albiero M, Baessol, et al. 2006. Diabetes impairs progenitor cell mobilisation after hindlimb ischaemia-reperfusion injury in rats. Diabetologia 49:3075-84