Kamat, Chandrashekhar D., Thorpe, Jessica E, Shenoy, Satyendra S, Ceriello, Antonio, Green, Dixy E., Warnke, Linda A. and Ihnat, Michael A.. (2007) A long-term "memory" of HIF induction in response to chronic mild decreased oxygen after oxygen normalization. BMC Cardiovascular Disorders, Vol.7 (No.4). ISSN 1471-2261

Preview

PDF WRAP_Ceriello_Long_Term_Memory.pdf - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader Download (716Kb)

Abstract

Background Endothelial dysfunction (ED) is functionally characterized by decreased vasorelaxation, increased thrombosis, increased inflammation, and altered angiogenic potential, has been intimately associated with the progression and severity of cardiovascular disease. Patients with compromised cardiac function oftentimes have a state of chronic mild decreased oxygen at the level of the vasculature and organs, which has been shown to exacerbate ED. Hypoxia inducible factor (HIF) is a transcription factor complex shown to be the master regulator of the cellular response to decreased oxygen levels and many HIF target genes have been shown to be associated with ED. Methods Human endothelial and aortic smooth muscle cells were exposed either to A) normoxia (21% O2) for three weeks, or to B) mild decreased oxygen (15% O2) for three weeks to mimic blood oxygen levels in patients with heart failure, or to C) mild decreased oxygen for two weeks followed by one week of normoxia ("memory" treatment). Levels of HIF signaling genes (HIF-1α, HIF-2α, VEGF, BNIP3, GLUT-1, PAI-1 and iNOS) were measured both at the protein and mRNA levels. Results It was found that chronic exposure to mild decreased oxygen resulted in significantly increased HIF signaling. There was also a "memory" of HIF-1α and HIF target gene induction when oxygen levels were normalized for one week, and this "memory" could be interrupted by adding a small molecule HIF inhibitor to the last week of normalized oxygen. Finally, levels of ubiquitylated HIF-1α were reduced in response to chronic mild decreased oxygen and were not full restored after oxygen normalization. Conclusion These data suggest that HIF signaling may be contributing to the pathogenesis of endothelial dysfunction and that normalization of oxygen levels may not be enough to reduce vascular stress.

Item Type:	Journal Article
Subjects:	R Medicine > R Medicine (General)
Divisions:	Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Endothelium, Cardiovascular system -- Diseases, Anoxemia
Journal or Publication Title:	BMC Cardiovascular Disorders
Publisher:	BioMed Central Ltd.
ISSN:	1471-2261
Date:	18 January 2007
Volume:	Vol.7
Number:	No.4
Identification Number:	10.1186/1471-2261-7-4
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	National Center for Research Resources (U.S.) (NCRR)
Grant number:	1P20RR017703-01
References:	1. Landmesser U, Hornig B, Drexler H: Endothelial function: a critical determinant in atherosclerosis? Circulation 2004, 109(21 Suppl 1):II27-33. 2. Aronson D, Rayfield EJ, Chesebro JH: Mechanisms determining course and outcome of diabetic patients who have had acute myocardial infarction. Ann Intern Med 1997, 126(4):296-306. 3. Bugiardini R, Manfrini O, Pizzi C, Fontana F, Morgagni G: Endothelial function predicts future development of coronary artery disease: a study of women with chest pain and normal coronary angiograms. Circulation 2004, 109(21):2518-2523. 4. Britland ST, Young RJ, Sharma AK, Clarke BF: Relationship of endoneurial capillary abnormalities to type and severity of diabetic polyneuropathy. Diabetes 1990, 39(8):909-913. 5. Farhangkhoee H, Khan ZA, Kaur H, Xin X, Chen S, Chakrabarti S: Vascular endothelial dysfunction in diabetic cardiomyopathy: Pathogenesis and potential treatment targets. Pharmacol Ther 2005. 6. Guay AT: Relation of endothelial cell function to erectile dysfunction: implications for treatment. Am J Cardiol 2005, 96(12B):52M-56M. 7. Szocs K: Endothelial dysfunction and reactive oxygen species production in ischemia/reperfusion and nitrate tolerance. Gen Physiol Biophys 2004, 23(3):265-295. 8. Meraji S, Jayakody L, Senaratne MP, Thomson AB, Kappagoda T: Endothelium-dependent relaxation in aorta of BB rat. Diabetes 1987, 36(8):978-981. 9. Schmetterer L, Findl O, Fasching P, Ferber W, Strenn K, Breiteneder H, Adam H, Eichler HG, Wolzt M: Nitric oxide and ocular blood flow in patients with IDDM. Diabetes 1997, 46(4):653-658. 10. Soriano FG, Virag L, Szabo C: Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species production and poly(ADP-ribose) polymerase activation. J Mol Med 2001, 79(8):437-448. 11. Felmeden DC, Lip GY: Endothelial function and its assessment. Expert Opin Investig Drugs 2005, 14(11):1319-1336. 12. Catrina SB, Okamoto K, Pereira T, Brismar K, Poellinger L: Hyperglycemia regulates hypoxia-inducible factor-1alpha protein stability and function. Diabetes 2004, 53(12):3226-3232. 13. Higashi Y, Nishioka K, Umemura T, Chayama K, Yoshizumi M: Oxidative stress, endothelial function and angiogenesis induced by cell therapy and gene therapy. Curr Pharm Biotechnol 2006, 7(2):109-116. 14. Dery MA, Michaud MD, Richard DE: Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators. Int J Biochem Cell Biol 2005, 37(3):535-540. 15. Wang GL, Jiang BH, Rue EA, Semenza GL: Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A 1995, 92(12):5510-5514. 16. Yu F, White SB, Zhao Q, Lee FS: HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proc Natl Acad Sci U S A 2001, 98(17):9630-9635. 17. Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER, Ratcliffe PJ: The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 1999, 399(6733):271-275. 18. Hara S, Hamada J, Kobayashi C, Kondo Y, Imura N: Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: suppression of HIF-mediated gene expression by HIF-3alpha. Biochem Biophys Res Commun 2001, 287(4):808-813. 19. Semenza GL: Angiogenesis in ischemic and neoplastic disorders. Annu Rev Med 2003, 54:17-28. 20. Haddad JJ, Olver RE, Land SC: Antioxidant/pro-oxidant equilibrium regulates HIF-1alpha and NF-kappa B redox sensitivity. Evidence for inhibition by glutathione oxidation in alveolar epithelial cells. J Biol Chem 2000, 275(28):21130-21139. 21. Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM, Schumacker PT: Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem 2000, 275(33):25130-25138. 22. Hagen T, Taylor CT, Lam F, Moncada S: Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1alpha. Science 2003, 302(5652):1975-1978. 23. Duyndam MC, Hulscher TM, Fontijn D, Pinedo HM, Boven E: Induction of vascular endothelial growth factor expression and hypoxia-inducible factor 1alpha protein by the oxidative stressor arsenite. J Biol Chem 2001, 276(51):48066-48076. 24. Salnikow K, Blagosklonny MV, Ryan H, Johnson R, Costa M: Carcinogenic nickel induces genes involved with hypoxic stress. Cancer Res 2000, 60(1):38-41. 25. Hellwig-Burgel T, Rutkowski K, Metzen E, Fandrey J, Jelkmann W: Interleukin-1beta and tumor necrosis factor-alpha stimulate DNA binding of hypoxia-inducible factor-1. Blood 1999, 94(5):1561-1567. 26. Jiang BH, Jiang G, Zheng JZ, Lu Z, Hunter T, Vogt PK: Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1. Cell Growth Differ 2001, 12(7):363-369. 27. Richard DE, Berra E, Gothie E, Roux D, Pouyssegur J: p42/p44 mitogen-activated protein kinases phosphorylate hypoxiainducible factor 1alpha (HIF-1alpha) and enhance the transcriptional activity of HIF-1. J Biol Chem 1999, 274(46):32631-32637. 28. Roy S, Sala R, Cagliero E, Lorenzi M: Overexpression of fibronectin induced by diabetes or high glucose: phenomenon with a memory. Proc Natl Acad Sci U S A 1990, 87(1):404-408. 29. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. Jama 2002, 287(19):2563-2569. 30. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. Jama 2003, 290(16):2159-2167. 31. Dilsizian V, Bateman TM, Bergmann SR, Des Prez R, Magram MY, Goodbody AE, Babich JW, Udelson JE: Metabolic imaging with beta-methyl-p-[(123)I]-iodophenyl-pentadecanoic acid identifies ischemic memory after demand ischemia. Circulation 2005, 112(14):2169-2174. 32. Strandberg TE, Pyorala K, Cook TJ, Wilhelmsen L, Faergeman O, Thorgeirsson G, Pedersen TR, Kjekshus J: Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S). Lancet 2004, 364(9436):771-777. 33. Bosch J, Lonn E, Pogue J, Arnold JM, Dagenais GR, Yusuf S: Longterm effects of ramipril on cardiovascular events and on diabetes: results of the HOPE study extension. Circulation 2005, 112(9):1339-1346. 34. Ades EW, Candal FJ, Swerlick RA, George VG, Summers S, Bosse DC, Lawley TJ: HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J Invest Dermatol 1992, 99(6):683-690. 35. Wang GL, Semenza GL: Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia. J Biol Chem 1993, 268(29):21513-21518. 36. Wang GL, Semenza GL: Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNAbinding activity: implications for models of hypoxia signal transduction. Blood 1993, 82(12):3610-3615. 37. Bierhaus A, Chevion S, Chevion M, Hofmann M, Quehenberger P, Illmer T, Luther T, Berentshtein E, Tritschler H, Muller M, Wahl P, Ziegler R, Nawroth PP: Advanced glycation end productinduced activation of NF-kappaB is suppressed by alphalipoic acid in cultured endothelial cells. Diabetes 1997, 46(9):1481-1490. 38. Barchowsky A, Klei LR, Dudek EJ, Swartz HM, James PE: Stimulation of reactive oxygen, but not reactive nitrogen species, in vascular endothelial cells exposed to low levels of arsenite. Free Radic Biol Med 1999, 27(11-12):1405-1412. 39. Zou MH, Klein T, Pasquet JP, Ullrich V: Interleukin 1beta decreases prostacyclin synthase activity in rat mesangial cells via endogenous peroxynitrite formation. Biochem J 1998, 336 ( Pt 2):507-512. 40. Yeo EJ, Chun YS, Cho YS, Kim J, Lee JC, Kim MS, Park JW: YC-1: a potential anticancer drug targeting hypoxia-inducible factor 1. J Natl Cancer Inst 2003, 95(7):516-525. 41. Zou MH, Kirkpatrick SS, Davis BJ, Nelson JS, Wiles WG, Schlattner U, Neumann D, Brownlee M, Freeman MB, Goldman MH: Activation of the AMP-activated protein kinase by the anti-diabetic drug metformin in vivo. Role of mitochondrial reactive nitrogen species. J Biol Chem 2004, 279(42):43940-43951. 42. Jiang M, Wang B, Wang C, He B, Fan H, Guo TB, Shao Q, Gao L, Liu Y: Inhibition of hypoxia-inducible factor-1alpha and endothelial progenitor cell differentiation by adenoviral transfer of small interfering RNA in vitro. J Vasc Res 2006, 43(6):511-521. 43. Pore N, Liu S, Shu HK, Li B, Haas-Kogan D, Stokoe D, Milanini-Mongiat J, Pages G, O'Rourke DM, Bernhard E, Maity A: Sp1 is involved in Akt-mediated induction of VEGF expression through an HIF-1-independent mechanism. Mol Biol Cell 2004, 15(11):4841-4853. 44. Zhang X, Kon T, Wang H, Li F, Huang Q, Rabbani ZN, Kirkpatrick JP, Vujaskovic Z, Dewhirst MW, Li CY: Enhancement of hypoxiainduced tumor cell death in vitro and radiation therapy in vivo by use of small interfering RNA targeted to hypoxiainducible factor-1alpha. Cancer Res 2004, 64(22):8139-8142. 45. Hurst RE, Kamat CD, Kyker KD, Green DE, Ihnat MA: A novel multidrug resistance phenotype of bladder tumor cells grown on Matrigel or SIS gel. Cancer Lett 2005, 217(2):171-180. 46. Timms RM, Kvale PA, Anthonisen NR, Boylen CT, Cugell DW, Petty TL, Williams GW: Selection of patients with chronic obstructive pulmonary disease for long-term oxygen therapy. In JAMA Volume 245. Issue 24 UNITED STATES ; 1981:2514-2515. 47. Young IH, Woolcock AJ: Arterial blood gas tension changes at the start of exercise in chronic obstructive pulmonary disease. In Am Rev Respir Dis Volume 119. Issue 2 UNITED STATES ; 1979:213-221. 48. Shepard JW: Gas exchange and hemodynamics during sleep. In Med Clin North Am Volume 69. Issue 6 UNITED STATES ; 1985:1243-1264. 49. Strickland RA, Hill TR, Zaloga GP: Bedside analysis of arterial blood gases and electrolytes during and after cardiac surgery. J Clin Anesth 1989, 1(4):248-252. 50. Gleadle JM, Ratcliffe PJ: Induction of hypoxia-inducible factor-1, erythropoietin, vascular endothelial growth factor, and glucose transporter-1 by hypoxia: evidence against a regulatory role for Src kinase. Blood 1997, 89(2):503-509. 51. Bruick RK: Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci U S A 2000, 97(16):9082-9087. 52. Kietzmann T, Roth U, Jungermann K: Induction of the plasminogen activator inhibitor-1 gene expression by mild hypoxia via a hypoxia response element binding the hypoxia-inducible factor-1 in rat hepatocytes. Blood 1999, 94(12):4177-4185. 53. Melillo G, Taylor LS, Brooks A, Musso T, Cox GW, Varesio L: Functional requirement of the hypoxia-responsive element in the activation of the inducible nitric oxide synthase promoter by the iron chelator desferrioxamine. J Biol Chem 1997, 272(18):12236-12243. 54. Liu Y, Cox SR, Morita T, Kourembanas S: Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5' enhancer. Circ Res 1995, 77(3):638-643. 55. Kietzmann T, Gorlach A: Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression. Semin Cell Dev Biol 2005, 16(4-5):474-486. 56. Kim HL, Yeo EJ, Chun YS, Park JW: A domain responsible for HIF-1alpha degradation by YC-1, a novel anticancer agent. Int J Oncol 2006, 29(1):255-260. 57. Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM: Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem 2004, 11(9):1135-1146. 58. Naseem KM: The role of nitric oxide in cardiovascular diseases. Mol Aspects Med 2005, 26(1-2):33-65. 59. Dvorak HF, Brown LF, Detmar M, Dvorak AM: Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995, 146(5):1029-1039. 60. Detmar M, Brown LF, Schon MP, Elicker BM, Velasco P, Richard L, Fukumura D, Monsky W, Claffey KP, Jain RK: Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice. J Invest Dermatol 1998, 111(1):1-6. 61. Vaughan DE: PAI-1 and atherothrombosis. J Thromb Haemost 2005, 3(8):1879-1883. 62. Kubasiak LA, Hernandez OM, Bishopric NH, Webster KA: Hypoxia and acidosis activate cardiac myocyte death through the Bcl- 2 family protein BNIP3. Proc Natl Acad Sci U S A 2002, 99(20):12825-12830. 63. Raval RR, Lau KW, Tran MG, Sowter HM, Mandriota SJ, Li JL, Pugh CW, Maxwell PH, Harris AL, Ratcliffe PJ: Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel- Lindau-associated renal cell carcinoma. Mol Cell Biol 2005, 25(13):5675-5686. 64. Sowter HM, Raval RR, Moore JW, Ratcliffe PJ, Harris AL: Predominant role of hypoxia-inducible transcription factor (Hif)- 1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia. Cancer Res 2003, 63(19):6130-6134. 65. Wang V, Davis DA, Haque M, Huang LE, Yarchoan R: Differential gene up-regulation by hypoxia-inducible factor-1alpha and hypoxia-inducible factor-2alpha in HEK293T cells. Cancer Res 2005, 65(8):3299-3306. 66. Sowter HM, Ratcliffe PJ, Watson P, Greenberg AH, Harris AL: HIF- 1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Res 2001, 61(18):6669-6673. 67. Calvani M, Rapisarda A, Uranchimeg B, Shoemaker RH, Melillo G: Hypoxic induction of a HIF-1{alpha}- dependent bFGF autocrine loop drives angiogenesis in human endothelial cells. Blood 2005. 68. Carroll VA, Ashcroft M: Role of hypoxia-inducible factor (HIF)- 1alpha versus HIF-2alpha in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-I, or loss of von Hippel-Lindau function: implications for targeting the HIF pathway. Cancer Res 2006, 66(12):6264-6270. 69. Kelley EE, Hock T, Khoo NK, Richardson GR, Johnson KK, Powell PC, Giles GI, Agarwal A, Lancaster JRJ, Tarpey MM: Moderate hypoxia induces xanthine oxidoreductase activity in arterial endothelial cells. Free Radic Biol Med 2006, 40(6):952-959. 70. Radi R: Nitric oxide, oxidants, and protein tyrosine nitration. Proc Natl Acad Sci U S A 2004, 101(12):4003-4008. 71. Appelhoff RJ, Tian YM, Raval RR, Turley H, Harris AL, Pugh CW, Ratcliffe PJ, Gleadle JM: Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxiainducible factor. J Biol Chem 2004, 279(37):38458-38465. 72. Callapina M, Zhou J, Schmid T, Kohl R, Brune B: NO restores HIF- 1alpha hydroxylation during hypoxia: role of reactive oxygen species. Free Radic Biol Med 2005, 39(7):925-936.
URI:	http://wrap.warwick.ac.uk/id/eprint/561

Request changes to a record

Actions (login required)

View Item