Vascular oxidative stress in aging: A homeostatic failure due to dysregulation of NRF2-mediated antioxidant response

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 301, Issue 2, 2011, Pages

  Ungvari, Zoltan ^a   Bailey Downs, Lora ^a   Sosnowska, Danuta ^a   Gautam, Tripti ^a   Koncz, Peter ^a   Losonczy, Gyorgy ^b   Ballabh, Praveen ^c   de Cabo, Rafael ^d   Sonntag, William E ^a   Csiszar, Anna ^a  

^a UNIVERSITY OF OKLAHOMA COLLEGE OF MEDICINE   (United States)

^b SEMMELWEIS UNIVERSITY   (Hungary)

^c NEW YORK MEDICAL COLLEGE   (United States)

^d NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

Apoptosis; Oxidative stress resistance; Senescence; Vascular injury

Indexed keywords

FREE RADICAL; GLUCOSE; GLUTAMATE CYSTEINE LIGASE; HEME OXYGENASE 1; HYDROGEN PEROXIDE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 6; MESSENGER RNA; OXYGEN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE) 1; TRANSCRIPTION FACTOR NRF2; UNCLASSIFIED DRUG;

AGING; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AORTA; ARTICLE; CONTROLLED STUDY; DETOXIFICATION; DISEASE ASSOCIATION; DOWN REGULATION; HOMEOSTASIS; ISOLATED ARTERY; NONHUMAN; OXIDATIVE STRESS; OXYGEN CONSUMPTION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN INDUCTION; PROTEIN TRANSPORT; RAT; TISSUE CULTURE; UPREGULATION; VASCULAR OXIDATIVE STRESS;

AGE FACTORS; AGING; ANALYSIS OF VARIANCE; ANIMALS; AORTA; APOPTOSIS; CAROTID ARTERIES; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GLUCOSE; GLUTAMATE-CYSTEINE LIGASE; HEME OXYGENASE (DECYCLIZING); HOMEOSTASIS; HYDROGEN PEROXIDE; HYPERGLYCEMIA; INTERCELLULAR ADHESION MOLECULE-1; INTERLEUKIN-6; MALE; NAD(P)H DEHYDROGENASE (QUINONE); NF-E2-RELATED FACTOR 2; NF-KAPPA B; OXIDATIVE STRESS; RATS; RATS, INBRED BN; RATS, INBRED F344; RNA, MESSENGER; TISSUE CULTURE TECHNIQUES;

EID: 79961043903     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.01134.2010     Document Type: Article

References (67)

1. Afonyushkin T, Oskolkova OV, Philippova M, Resink TJ, Erne P, Binder BR, Bochkov VN. Oxidized phospholipids regulate expression of ATF4 and VEGF in endothelial cells via NRF2-dependent mechanism: novel point of convergence between electrophilic and unfolded protein stress pathways. Arterioscler Thromb Vasc Biol 30: 1007-1013, 2010.
2. Bloomer SA, Zhang HJ, Brown KE, Kregel KC. Differential regulation of hepatic heme oxygenase-1 protein with aging and heat stress. J Gerontol A Biol Sci Med Sci 64: 419-425, 2009.
3. Bruce DG, Davis WA, Casey GP, Starkstein SE, Clarnette RM, Almeida OP, Davis TM. Predictors of cognitive decline in older individuals with diabetes. Diabetes care 31: 2103-2107, 2008.
4. Campisi J, Vijg J. Does damage to DNA and other macromolecules play a role in aging? If so, how? J Gerontol A Biol Sci Med Sci 64: 175-178, 2009.
5. Chen CN, Brown-Borg HM, Rakoczy SG, Ferrington DA, Thompson LV. Aging impairs the expression of the catalytic subunit of glutamate cysteine ligase in soleus muscle under stress. J Gerontol A Biol Sci Med Sci 65: 129-137, 2010.
6. Chen XL, Varner SE, Rao AS, Grey JY, Thomas S, Cook CK, Wasserman MA, Medford RM, Jaiswal AK, Kunsch C. Laminar flow induction of antioxidant response element-mediated genes in endothelial cells. A novel anti-inflammatory mechanism. The Journal of biological chemistry 278: 703-711, 2003.
7. Collins AR, Lyon CJ, Xia X, Liu JZ, Tangirala RK, Yin F, Boyadjian R, Bikineyeva A, Pratico D, Harrison DG, Hsueh WA. Age-accelerated atherosclerosis correlates with failure to upregulate antioxidant genes. Circ Res 104: e42-e54, 2009.
8. Csiszar A, Labinskyy N, Jimenez R, Pinto JT, Ballabh P, Losonczy G, Pearson KJ, de Cabo R, Ungvari Z. Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1. Mech Ageing Dev, 2009.
9. Csiszar A, Labinskyy N, Orosz Z, Xiangmin Z, Buffenstein R, Ungvari Z. Vascular aging in the longest-living rodent, the naked mole-rat. Am J Physiol Heart Circ Physiol 293: H919-H927, 2007.
10. Csiszar A, Labinskyy N, Perez V, Recchia FA, Podlutsky A, Mukhopadhyay P, Losonczy G, Pacher P, Austad SN, Bartke A, Ungvari Z. Endothelial function and vascular oxidative stress in long-lived GH/IGFdeficient Ames dwarf mice. Am J Physiol Heart Circ Physiol 295: H1882-H1894, 2008.
11. Csiszar A, Labinskyy N, Smith K, Rivera A, Orosz Z, Ungvari Z. Vasculoprotective effects of anti-TNFalpha treatment in aging. The American journal of pathology 170: 388-398, 2007.
12. Csiszar A, Labinskyy N, Zhao X, Hu F, Serpillon S, Huang Z, Ballabh P, Levy RJ, Hintze TH, Wolin MS, Austad SN, Podlutsky A, Ungvari Z. Vascular superoxide and hydrogen peroxide production and oxidative stress resistance in two closely related rodent species with disparate longevity. Aging Cell 6: 783-797, 2007.
13. Csiszar A, Smith K, Labinskyy N, Orosz Z, Rivera A, Ungvari Z. Resveratrol attenuates TNF--induced activation of coronary arterial endothelial cells: role of NF-κB inhibition. Am J Physiol Heart Circ Physiol 291: H1694-H1699, 2006.
14. Csiszar A, Smith KE, Koller A, Kaley G, Edwards JG, Ungvari Z. Regulation of bone morphogenetic protein-2 expression in endothelial cells: role of nuclear factor-kappaB activation by tumor necrosis factoralpha, H2O2, and high intravascular pressure. Circulation 111: 2364-2372, 2005.
15. Csiszar A, Ungvari Z, Edwards JG, Kaminski PM, Wolin MS, Koller A, Kaley G. Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function. Circ Res 90: 1159-1166, 2002.
16. Csiszar A, Ungvari Z, Koller A, Edwards JG, Kaley G. Proinflammatory phenotype of coronary arteries promotes endothelial apoptosis in aging. Physiol Genomics 17: 21-30, 2004.
17. Csiszar A, Wang M, Lakatta EG, Ungvari ZI. Inflammation and endothelial dysfunction during aging: role of NF-κB. J Appl Physiol 105: 1333-1341, 2008.
18. Donato AJ, Eskurza I, Silver AE, Levy AS, Pierce GL, Gates PE, Seals DR. Direct evidence of endothelial oxidative stress with aging in humans: relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-kappaB. Circulation research 100: 1659-1666, 2007.
19. Eskurza I, Kahn ZD, Seals DR. Xanthine oxidase does not contribute to impaired peripheral conduit artery endothelium-dependent dilatation with ageing. The Journal of physiology 571: 661-668, 2006.
20. Eskurza I, Monahan KD, Robinson JA, Seals DR. Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing. The Journal of physiology 556: 315-324, 2004.
21. Fledderus JO, Boon RA, Volger OL, Hurttila H, Yla-Herttuala S, Pannekoek H, Levonen AL, Horrevoets AJ. KLF2 primes the antioxidant transcription factor Nrf2 for activation in endothelial cells. Arterioscler Thromb Vasc Biol 28: 1339-1346, 2008.
22. Fledderus JO, Boon RA, Volger OL, Hurttila H, Yla-Herttuala S, Pannekoek H, Levonen AL, Horrevoets AJ. KLF2 primes the antioxidant transcription factor Nrf2 for activation in endothelial cells. Arterioscler Thromb Vasc Biol 28: 1339-1346, 2008.
23. Francia P, delli Gatti C, Bachschmid M, Martin-Padura I, Savoia C, Migliaccio E, Pelicci PG, Schiavoni M, Luscher TF, Volpe M, Cosentino F. Deletion of p66shc gene protects against age-related endothelial dysfunction. Circulation 110: 2889-2895, 2004.
24. Gates PE, Boucher ML, Silver AE, Monahan KD, Seals DR. Impaired flow-mediated dilation with age is not explained by L-arginine bioavailability or endothelial asymmetric dimethylarginine protein expression. J Appl Physiol 102: 63-71, 2007.
25. Hamilton CA, Brosnan MJ, McIntyre M, Graham D, Dominiczak AF. Superoxide excess in hypertension and aging: a common cause of endothelial dysfunction. Hypertension 37: 529-534, 2001.
26. He X, Kan H, Cai L, Ma Q. Nrf2 is critical in defense against high glucose-induced oxidative damage in cardiomyocytes. J Mol Cell Cardiol 46: 47-58, 2009.
27. Jablonski KL, Seals DR, Eskurza I, Monahan KD, Donato AJ. Highdose ascorbic acid infusion abolishes chronic vasoconstriction and restores resting leg blood flow in healthy older men. J Appl Physiol 103: 1715-1721, 2007.
28. Jang YC, Perez VI, Song W, Lustgarten MS, Salmon AB, Mele J, Qi W, Liu Y, Liang H, Chaudhuri A, Ikeno Y, Epstein CJ, Van Remmen H, Richardson A. Overexpression of Mn superoxide dismutase does not increase life span in mice. J Gerontol A Biol Sci Med Sci 64: 1114-1125, 2009.
29. Jasper H. SKNy worms and long life. Cell 132: 915-916, 2008.
30. Jyrkkanen HK, Kansanen E, Inkala M, Kivela AM, Hurttila H, Heinonen SE, Goldsteins G, Jauhiainen S, Tiainen S, Makkonen H, Oskolkova O, Afonyushkin T, Koistinaho J, Yamamoto M, Bochkov VN, Yla-Herttuala S, Levonen AL. Nrf2 regulates antioxidant gene expression evoked by oxidized phospholipids in endothelial cells and murine arteries in vivo. Circ Res 103: e1-e9, 2008.
31. 2 production, and vascular oxidative stress resistance between the longest-living rodent, the naked mole rat, and mice. Am J Physiol Heart Circ Physiol 291: H2698-H2704, 2006.
32. Labinskyy N, Mukhopadhyay P, Toth J, Szalai G, Veres M, Losonczy G, Pinto JT, Pacher P, Ballabh P, Podlutsky A, Austad SN, Csiszar A, Ungvari Z. Longevity is associated with increased vascular resistance to high glucose-induced oxidative stress and inflammatory gene expression in Peromyscus leucopus. Am J Physiol Heart Circ Physiol 296: H946- H956, 2009.
33. Lewis KN, Mele J, Hayes JD, Buffenstein R. Nrf2, a guardian of healthspan and gatekeeper of species longevity. Integr Comp Biol 50: 829-843, 2010.
34. Miller RA. Cell stress and aging: new emphasis on multiplex resistance mechanisms. J Gerontol A Biol Sci Med Sci 64: 179-182, 2009.
35. Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R, Fernandez E, Flurkey K, Javors MA, Nelson JF, Orihuela CJ, Pletcher S, Sharp ZD, Sinclair D, Starnes JW, Wilkinson JE, Nadon NL, Strong R. Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci 66: 191-201, 2011.
36. Mukhopadhyay P, Rajesh M, Hasko G, Hawkins BJ, Madesh M, Pacher P. Simultaneous detection of apoptosis and mitochondrial superoxide production in live cells by flow cytometry and confocal microscopy. Nat Protoc 2: 2295-2301, 2007.
37. Okouchi M, Okayama N, Alexander JS, Aw TY. NRF2-dependent glutamate-L-cysteine ligase catalytic subunit expression mediates insulin protection against hyperglycemia-induced brain endothelial cell apoptosis. Curr Neurovasc Res 3: 249-261, 2006.
38. Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87: 315-424, 2007.
39. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 8: 157-168, 2008.
40. Pearson KJ, Lewis KN, Price NL, Chang JW, Perez E, Cascajo MV, Tamashiro KL, Poosala S, Csiszar A, Ungvari Z, Kensler TW, Yamamoto M, Egan JM, Longo DL, Ingram DK, Navas P, de Cabo R. Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction. Proc Natl Acad Sci USA 105: 2325-2330, 2008.
41. Ryan MJ, Jackson JR, Hao Y, Williamson CL, Dabkowski ER, Hollander JM, Alway SE. Suppression of oxidative stress by resveratrol after isometric contractions in gastrocnemius muscles of aged mice. J Gerontol A Biol Sci Med Sci 65: 815-831, 2010.
42. Suh JH, Shenvi SV, Dixon BM, Liu H, Jaiswal AK, Liu RM, Hagen TM. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci USA 101: 3381-3386, 2004.
43. Sun D, Huang A, Yan EH, Wu Z, Yan C, Kaminski PM, Oury TD, Wolin MS, Kaley G. Reduced release of nitric oxide to shear stress in mesenteric arteries of aged rats. Am J Physiol Heart Circ Physiol 286: H2249-H2256, 2004.
44. Sykiotis GP, Bohmann D. Keap1/Nrf2 signaling regulates oxidative stress tolerance and lifespan in Drosophila. Dev Cell 14: 76-85, 2008.
45. Szabo C, Zanchi A, Komjati K, Pacher P, Krolewski AS, Quist WC, LoGerfo FW, Horton ES, Veves A. Poly(ADP-Ribose) polymerase is activated in subjects at risk of developing type 2 diabetes and is associated with impaired vascular reactivity. Circulation 106: 2680-2686, 2002.
46. Ungvari Z, Bagi Z, Feher A, Recchia FA, Sonntag WE, Pearson K, de Cabo R, Csiszar A. Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2. Am J Physiol Heart Circ Physiol 299: H18-H24, 2010.
47. Ungvari Z, Bailey-Downs L, Gautam T, Jimenez J, Losonczy G, Zhang C, Ballabh P, Recchia FA, Wilkerson DC, Sonntag WE, Pearson K, de Cabo R, Csiszar A. Adaptive induction of NF-E2-Related Factor-2-driven antioxidant genes in endothelial cells in response to hyperglycemia. Am J Physiol Heart Circ Physiol 300: H1133-H1140, 2011.
48. Ungvari Z, Bailey-Downs L, Gautam T, Sosnowska D, Wang M, Monticone RE, Telljohann R, Pinto JT, de Cabo R, Sonntag WE, Lakatta E, Csiszar A. Age-associated vascular oxidative stress, Nrf2 dysfunction and NF-kB activation in the non-human primate Macaca mulatta. J Gerontol Biol Med Sci. 2011, doi:10.1093/gerona/glr092.
49. Ungvari Z, Buffenstein R, Austad SN, Podlutsky A, Kaley G, Csiszar A. Oxidative stress in vascular senescence: lessons from successfully aging species. Front Biosci 13: 5056-5070, 2008.
50. Ungvari Z, Csiszar A, Huang A, Kaminski PM, Wolin MS, Koller A. High pressure induces superoxide production in isolated arteries via protein kinase C-dependent activation of NAD(P)H oxidase. Circulation 108: 1253-1258, 2003.
51. Ungvari Z, Gautam T, Koncz P, Henthorn JC, Pinto JT, Ballabh P, Yan H, Mitschelen M, Farley J, Sonntag WE, Csiszar A. Vasoprotective effects of life span-extending peripubertal GH replacement in Lewis dwarf rats. J Gerontol A Biol Sci Med Sci 65: 1145-1156, 2010.
52. Ungvari Z, Kaley G, de Cabo R, Sonntag WE, Csiszar A. Mechanisms of vascular aging: new perspectives. J Gerontol A Biol Sci Med Sci 65: 1028-1041, 2010.
53. Ungvari Z, Krasnikov BF, Csiszar A, Labinskyy N, Mukhopadhyay P, Pacher P, Cooper AJL, Podlutskaya N, Austad SN, Podlutsky A. Testing hypotheses of aging in long-lived mice of the genus Peromyscus: association between longevity and mitochondrial stress resistance, ROS detoxification pathways and DNA repair efficiency. Age (Dordr) 30: 121-133, 2008.
54. Ungvari Z, Labinskyy N, Mukhopadhyay P, Pinto JT, Bagi Z, Ballabh P, Zhang C, Pacher P, Csiszar A. Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells. Am J Physiol Heart Circ Physiol 297: H1876-H1881, 2009.
55. Ungvari Z, Orosz Z, Labinskyy N, Rivera A, Xiangmin Z, Smith K, Csiszar A. Increased mitochondrial H2O2 production promotes endothelial NF-κB activation in aged rat arteries. Am J Physiol Heart Circ Physiol 293: H37-H47, 2007.
56. Ungvari Z, Orosz Z, Rivera A, Labinskyy N, Xiangmin Z, Olson S, Podlutsky A, Csiszar A. Resveratrol increases vascular oxidative stress resistance. Am J Physiol Heart Circ Physiol 292: H2417-H2424, 2007.
57. Ungvari Z, Parrado-Fernandez C, Csiszar A, de Cabo R. Mechanisms underlying caloric restriction and lifespan regulation: implications for vascular aging. Circ Res 102: 519-528, 2008.
58. Ungvari ZI, Labinskyy N, Gupte SA, Chander PN, Edwards JG, Csiszar A. Dysregulation of mitochondrial biogenesis in vascular endothelial and smooth muscle cells of aged rats. Am J Physiol Heart Circ Physiol 294: H2121-H2128, 2008.
59. Ungvari ZI, Orosz Z, Labinskyy N, Rivera A, Xiangmin Z, Smith KE, Csiszar A. Increased mitochondrial H2O2 production promotes endothelial NF-κB activation in aged rat arteries. Am J Physiol Heart Circ Physiol 293: H37-H47, 2007.
60. van der Loo B, Labugger R, Skepper JN, Bachschmid M, Kilo J, Powell JM, Palacios-Callender M, Erusalimsky JD, Quaschning T, Malinski T, Gygi D, Ullrich V, Lüscher TF. Enhanced peroxynitrite formation is associated with vascular aging. J Exp Med 192: 1731-1744, 2000.
61. Warabi E, Takabe W, Minami T, Inoue K, Itoh K, Yamamoto M, Ishii T, Kodama T, Noguchi N. Shear stress stabilizes NF-E2-related factor 2 and induces antioxidant genes in endothelial cells: role of reactive oxygen/ nitrogen species. Free radical biology & medicine 42: 260-269, 2007.
62. Xue M, Qian Q, Antonysunil A, Rabbani N, Babaei-Jadidi R, Thornalley PJ. Activation of NF-E2-related factor-2 reverses biochemical dysfunction of endothelial cells induced by hyperglycemia linked to vascular disease. Diabetes 57: 2809-2817, 2008.
63. Yoh K, Hirayama A, Ishizaki K, Yamada A, Takeuchi M, Yamagishi S, Morito N, Nakano T, Ojima M, Shimohata H, Itoh K, Takahashi S, Yamamoto M. Hyperglycemia induces oxidative and nitrosative stress and increases renal functional impairment in Nrf2-deficient mice. Genes Cells 13: 1159-1170, 2008.
64. Zakkar M, Van der Heiden K, Luong LA, Chaudhury H, Cuhlmann S, Hamdulay SS, Krams R, Edirisinghe I, Rahman I, Carlsen H, Haskard DO, Mason JC, Evans PC. Activation of Nrf2 in endothelial cells protects arteries from exhibiting a proinflammatory state. Arterioscler Thromb Vasc Biol 29: 1851-1857, 2009.
65. Zhang H, Morgan B, Potter BJ, Ma L, Dellsperger KC, Ungvari ZI, Zhang C. Resveratrol improves left ventricular diastolic relaxation in type 2 diabetes by inhibiting oxidative/nitrative stress. Am J Physiol Heart Circ Physiol 299: H985-H994, 2010.
66. Zhang H, Zhang J, Ungvari Z, Zhang C. Resveratrol improves endothelial function: role of TNF and vascular oxidative stress. Arterioscler Thromb Vasc Biol 29: 1164-1171, 2009.
67. Zhang Y, Ikeno Y, Qi W, Chaudhuri A, Li Y, Bokov A, Thorpe SR, Baynes JW, Epstein C, Richardson A, Van Remmen H. Mice deficient in both Mn superoxide dismutase and glutathione peroxidase-1 have increased oxidative damage and a greater incidence of pathology but no reduction in longevity. J Gerontol A Biol Sci Med Sci 64: 1212-1220, 2009.