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Cited by 257Nitric Oxide and Endothelin EffectsMitochondrial Function and PathologyCardiovascular Health and Disease Prevention

Mitochondrial Oxidative Stress, Mitochondrial DNA Damage and Their Role in Age-Related Vascular Dysfunction

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Mikhed, Yuliya, Daiber, Andreas, Steven, Sebastian·2015·International Journal of Molecular Sciences
DOI 10.3390/ijms160715918PMC PMC4519931
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Abstract

The prevalence of cardiovascular diseases is significantly increased in the older population. Risk factors and predictors of future cardiovascular events such as hypertension, atherosclerosis, or diabetes are observed with higher frequency in elderly individuals. A major determinant of vascular aging is endothelial dysfunction, characterized by impaired endothelium-dependent signaling processes. Increased production of reactive oxygen species (ROS) leads to oxidative stress, loss of nitric oxide (•NO) signaling, loss of endothelial barrier function and infiltration of leukocytes to the vascular wall, explaining the low-grade inflammation characteristic for the aged vasculature. We here discuss the importance of different sources of ROS for vascular aging and their contribution to the increased cardiovascular risk in the elderly population with special emphasis on mitochondrial ROS formation and oxidative damage of mitochondrial DNA. Also the interaction (crosstalk) of mitochondria with nicotinamide adenosine dinucleotide phosphate (NADPH) oxidases is highlighted. Current concepts of vascular aging, consequences for the development of cardiovascular events and the particular role of ROS are evaluated on the basis of cell culture experiments, animal studies and clinical trials. Present data point to a more important role of oxidative stress for the maximal healthspan (healthy aging) than for the maximal lifespan.

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  • Ageing is characterised by increased production of ROS due to mitochondrial dysfunction and inflammageing, alongside reduced antioxidant capacity.

    “Ageing is characterised by increased production of reactive oxygen species (ROS) due to mitochondrial dysfunction and inflammageing, alongside reduced antioxidant capacity [253,254,255].”

    From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [253]

    Sections 3 and 7 report that mitochondrial ROS increases with age and that antioxidant MnSOD is inhibited in aging vessels. Section 4 links elevated inflammatory TNF-α in aged animals and humans to ROS production. These passages support the claim for the aging vasculature, but do not establish a general decline in antioxidant capacity throughout the body. (LLM, conf=0.83)

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  1. [1]Kelly D.T. Paul dudley white international lecture. Our future society. A global challenge Circulation 1997 95 2459 2464 10.1161/01.CIR.95.11.2459 9184571 · DOI
  2. [3]Ras R.T. Streppel M.T. Draijer R. Zock P.L. Flow-mediated dilation and cardiovascular risk prediction: A systematic review with meta-analysis Int. J. Cardiol. 2013 168 344 351 10.1016/j.ijcard.2012.09.047 23041097 · DOI
  3. [4]Herrera M.D. Mingorance C. Rodriguez-Rodriguez R. Alvarez de Sotomayor M. Endothelial dysfunction and aging: An update Ageing Res. Rev. 2010 9 142 152 10.1016/j.arr.2009.07.002 19619671 · DOI
  4. [5]Bischoff B. Silber S. Richartz B.M. Pieper L. Klotsche J. Wittchen H.U. Inadequate medical treatment of patients with coronary artery disease by primary care physicians in germany Clin. Res. Cardiol. 2006 95 405 412 10.1007/s00392-006-0399-2 16799879 · DOI
  5. [6]Burnett A.L. The role of nitric oxide in erectile dysfunction: Implications for medical therapy J. Clin. Hypertens. 2006 8 53 62 10.1111/j.1524-6175.2006.06026.x PMC8109295 17170606 · DOI
  6. [8]Price J.M. Hellermann A. Hellermann G. Sutton E.T. Aging enhances vascular dysfunction induced by the alzheimer’s peptide β-amyloid Neurol. Res. 2004 26 305 311 10.1179/016164104225014003 15142324 · DOI
  7. [9]Coleman H.R. Chan C.C. Ferris F.L. III Chew E.Y. Age-related macular degeneration Lancet 2008 372 1835 1845 10.1016/S0140-6736(08)61759-6 19027484 PMC2603424 · DOI · Paper page
  8. [10]El Assar M. Angulo J. Rodriguez-Manas L. Oxidative stress and vascular inflammation in aging Free Radic. Biol. Med. 2013 65 380 401 10.1016/j.freeradbiomed.2013.07.003 23851032 · DOI
  9. [11]Cesari M. Onder G. Russo A. Zamboni V. Barillaro C. Ferrucci L. Pahor M. Bernabei R. Landi F. Comorbidity and physical function: Results from the aging and longevity study in the Sirente geographic area (iLSIRENTE study) Gerontology 2006 52 24 32 10.1159/000089822 16439821 · DOI
  10. [12]Yancik R. Ershler W. Satariano W. Hazzard W. Cohen H.J. Ferrucci L. Report of the national institute on aging task force on comorbidity J. Gerontol. Ser. A 2007 62 275 280 10.1093/gerona/62.3.275 PMC2645628 17389724 · DOI
  11. [13]Wieland G.D. From bedside to bench: Research in comorbidity and aging Sci. Aging Knowl. Environ. 2005 2005 pe29 10.1126/sageke.2005.39.pe29 16192469 · DOI
  12. [14]Munzel T. Daiber A. Mulsch A. Explaining the phenomenon of nitrate tolerance Circ. Res. 2005 97 618 628 10.1161/01.RES.0000184694.03262.6d 16195486 · DOI · Paper page
  13. [15]Munzel T. Daiber A. Ullrich V. Mulsch A. Vascular consequences of endothelial nitric oxide synthase uncoupling for the activity and expression of the soluble guanylyl cyclase and the cGMP-dependent protein kinase Arterioscler. Thromb. Vasc. Biol. 2005 25 1551 1557 10.1161/01.ATV.0000168896.64927.bb 15879305 · DOI
  14. [16]Oelze M. Kroller-Schon S. Steven S. Lubos E. Doppler C. Hausding M. Tobias S. Brochhausen C. Li H. Torzewski M. Glutathione peroxidase-1 deficiency potentiates dysregulatory modifications of endothelial nitric oxide synthase and vascular dysfunction in aging Hypertension 2014 63 390 396 10.1161/HYPERTENSIONAHA.113.01602 24296279 · DOI
  15. [17]Van der Loo B. Labugger R. Skepper J.N. Bachschmid M. Kilo J. Powell J.M. Palacios-Callender M. Erusalimsky J.D. Quaschning T. Malinski T. Enhanced peroxynitrite formation is associated with vascular aging J. Exp. Med. 2000 192 1731 1744 10.1084/jem.192.12.1731 11120770 PMC2213492 · DOI
  16. [18]Forstermann U. Sessa W.C. Nitric oxide synthases: Regulation and function Eur. Heart J. 2012 33 829 837 10.1093/eurheartj/ehr304 21890489 PMC3345541 · DOI · Paper page
  17. [19]Daiber A. Oelze M. Daub S. Steven S. Schuff A. Kroller-Schon S. Hausding M. Wenzel P. Schulz E. Gori T. Vascular redox signaling, redox switches in endothelial nitric oxide synthase and endothelial dysfunction Systems Biology of Free Radicals and Antioxidants Laher I. Springer-Verlag Berlin, Germany; Heidelberg, Germany 2014 1177 1211
  18. [20]Donato A.J. Gano L.B. Eskurza I. Silver A.E. Gates P.E. Jablonski K. Seals D.R. Vascular endothelial dysfunction with aging: Endothelin-1 and endothelial nitric oxide synthase Am. J. Phys. Heart Circ. Physiol. 2009 297 H425 H432 10.1152/ajpheart.00689.2008 19465546 PMC2711733 · DOI
  19. [21]Donato A.J. Magerko K.A. Lawson B.R. Durrant J.R. Lesniewski L.A. Seals D.R. SIRT-1 and vascular endothelial dysfunction with ageing in mice and humans J. Physiol. 2011 589 4545 4554 10.1113/jphysiol.2011.211219 21746786 PMC3208223 · DOI
  20. [22]Higashi Y. Sasaki S. Nakagawa K. Kimura M. Noma K. Hara K. Jitsuiki D. Goto C. Oshima T. Chayama K. Tetrahydrobiopterin improves aging-related impairment of endothelium-dependent vasodilation through increase in nitric oxide production Atherosclerosis 2006 186 390 395 10.1016/j.atherosclerosis.2005.07.025 16129443 · DOI
  21. [23]Wenzel P. Schuhmacher S. Kienhofer J. Muller J. Hortmann M. Oelze M. Schulz E. Treiber N. Kawamoto T. Scharffetter-Kochanek K. Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction Cardiovasc. Res. 2008 80 280 289 10.1093/cvr/cvn182 18596060 PMC3937602 · DOI · Paper page
  22. [24]Gerhard M. Roddy M.A. Creager S.J. Creager M.A. Aging progressively impairs endothelium-dependent vasodilation in forearm resistance vessels of humans Hypertension 1996 27 849 853 10.1161/01.HYP.27.4.849 8613259 · DOI
  23. [25]Heitzer T. Schlinzig T. Krohn K. Meinertz T. Munzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease Circulation 2001 104 2673 2678 10.1161/hc4601.099485 11723017 · DOI · Paper page
  24. [26]Savji N. Rockman C.B. Skolnick A.H. Guo Y. Adelman M.A. Riles T. Berger J.S. Association between advanced age and vascular disease in different arterial territories: A population database of over 3.6 million subjects J. Am. Coll. Cardiol. 2013 61 1736 1743 10.1016/j.jacc.2013.01.054 23500290 · DOI
  25. [28]Daiber A. Kienhoefer J. Zee R. Ullrich V. van der Loo B. Bachschmid M. The role of mitochondrial reactive oxygen species formation for age-induced vascular dysfunction Aging and Age-Related Disorders Bondy S.C. Maiese K. Humana Press Clifton, NJ, USA 2010 237 257
  26. [29]Cadenas E. Davies K.J. Mitochondrial free radical generation, oxidative stress, and aging Free Radic. Biol. Med. 2000 29 222 230 10.1016/S0891-5849(00)00317-8 11035250 · DOI · Paper page
  27. [30]Lenaz G. Bovina C. D’Aurelio M. Fato R. Formiggini G. Genova M.L. Giuliano G. Pich M.M. Paolucci U. Castelli G.P. Role of mitochondria in oxidative stress and aging Ann. N. Y. Acad. Sci. 2002 959 199 213 10.1111/j.1749-6632.2002.tb02094.x 11976197 · DOI
  28. [31]Kujoth G.C. Hiona A. Pugh T.D. Someya S. Panzer K. Wohlgemuth S.E. Hofer T. Seo A.Y. Sullivan R. Jobling W.A. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging Science 2005 309 481 484 10.1126/science.1112125 16020738 · DOI · Paper page
  29. [32]Yin F. Boveris A. Cadenas E. Mitochondrial energy metabolism and redox signaling in brain aging and neurodegeneration Antioxid. Redox Signal. 2014 20 353 371 10.1089/ars.2012.4774 22793257 PMC3887431 · DOI
  30. [33]Cheng Z.J. Vapaatalo H. Mervaala E. Angiotensin II and vascular inflammation Med. Sci. Monit. 2005 11 RA194 RA205 15917731
  31. [34]Lau D. Baldus S. Myeloperoxidase and its contributory role in inflammatory vascular disease Pharmacol. Ther. 2006 111 16 26 10.1016/j.pharmthera.2005.06.023 16476484 · DOI
  32. [35]Willerson J.T. Golino P. Eidt J. Campbell W.B. Buja L.M. Specific platelet mediators and unstable coronary artery lesions. Experimental evidence and potential clinical implications Circulation 1989 80 198 205 10.1161/01.CIR.80.1.198 2661053 · DOI
  33. [37]Tanaka H. Dinenno F.A. Seals D.R. Age-related increase in femoral intima-media thickness in healthy humans Arterioscler. Thromb. Vasc. Biol. 2000 20 2172 10.1161/01.ATV.20.9.2172 10978266 · DOI
  34. [38]Crimi E. Ignarro L.J. Napoli C. Microcirculation and oxidative stress Free Radic. Res. 2007 41 1364 1375 10.1080/10715760701732830 18075839 · DOI
  35. [39]Mayhan W.G. Arrick D.M. Sharpe G.M. Sun H. Age-related alterations in reactivity of cerebral arterioles: Role of oxidative stress Microcirculation 2008 15 225 236 10.1080/10739680701641421 18386218 · DOI
  36. [40]Militante J. Lombardini J.B. Age-related retinal degeneration in animal models of aging: Possible involvement of taurine deficiency and oxidative stress Neurochem. Res. 2004 29 151 160 10.1023/B:NERE.0000010444.97959.1b 14992274 · DOI
  37. [41]Fischer R. Maier O. Interrelation of oxidative stress and inflammation in neurodegenerative disease: Role of TNF Oxidative Med. Cell. Longev. 2015 2015 610813 10.1155/2015/610813 25834699 PMC4365363 · DOI
  38. [42]Blasiak J. Petrovski G. Vereb Z. Facsko A. Kaarniranta K. Oxidative stress, hypoxia, and autophagy in the neovascular processes of age-related macular degeneration BioMed. Res. Int. 2014 2014 768026 10.1155/2014/768026 24707498 PMC3950832 · DOI
  39. [43]Harman D. Aging: A theory based on free radical and radiation chemistry J. Gerontol. 1956 11 298 300 10.1093/geronj/11.3.298 13332224 · DOI · Paper page
  40. [44]Waters W.A. Some recent developments in the chemistry of free radicals J. Chem. Soc. 1946 409 415 10.1039/jr9460000409 20988305 · DOI
  41. [45]Rogell B. Dean R. Lemos B. Dowling D.K. Mito-nuclear interactions as drivers of gene movement on and off the X-chromosome BMC Genomics 2014 15 330 10.1186/1471-2164-15-330 24885291 PMC4035061 · DOI
  42. [47]Van der Loo B. Bachschmid M. Skepper J.N. Labugger R. Schildknecht S. Hahn R. Mussig E. Gygi D. Luscher T.F. Age-associated cellular relocation of Sod 1 as a self-defense is a futile mechanism to prevent vascular aging Biochem. Biophys. Res. Commun. 2006 344 972 980 10.1016/j.bbrc.2006.03.224 16631605 · DOI
  43. [48]De Haan J.B. Bladier C. Lotfi-Miri M. Taylor J. Hutchinson P. Crack P.J. Hertzog P. Kola I. Fibroblasts derived from Gpx1 knockout mice display senescent-like features and are susceptible to H2O2-mediated cell death Free Radic. Biol. Med. 2004 36 53 64 10.1016/j.freeradbiomed.2003.10.020 14732290 · DOI
  44. [49]Altschmied J. Haendeler J. Thioredoxin-1 and endothelial cell aging: Role in cardiovascular diseases Antioxid. Redox Signal. 2009 11 1733 1740 10.1089/ars.2008.2379 19187002 · DOI
  45. [50]Go Y.M. Jones D.P. Redox control systems in the nucleus: Mechanisms and functions Antioxid. Redox Signal. 2010 13 489 509 10.1089/ars.2009.3021 20210649 PMC2935340 · DOI
  46. [51]Salmon A.B. Richardson A. Perez V.I. Update on the oxidative stress theory of aging: Does oxidative stress play a role in aging or healthy aging? Free Radic. Biol. Med. 2010 48 642 655 10.1016/j.freeradbiomed.2009.12.015 20036736 PMC2819595 · DOI
  47. [52]Brown K.A. Didion S.P. Andresen J.J. Faraci F.M. Effect of aging, MnSOD deficiency, and genetic background on endothelial function: Evidence for MnSOD haploinsufficiency Arterioscler. Thromb. Vasc. Biol. 2007 27 1941 1946 10.1161/ATVBAHA.107.146852 17556650 · DOI
  48. [53]Didion S.P. Kinzenbaw D.A. Schrader L.I. Faraci F.M. Heterozygous CuZn superoxide dismutase deficiency produces a vascular phenotype with aging Hypertension 2006 48 1072 1079 10.1161/01.HYP.0000247302.20559.3a 17043164 · DOI
  49. [54]Goldstein S. Czapski G. Lind J. Merenyi G. Tyrosine nitration by simultaneous generation of •NO and O•2 under physiological conditions. How the radicals do the job J. Biol. Chem. 2000 275 3031 3036 10.1074/jbc.275.5.3031 10652282 · DOI · Paper page
  50. [55]Perez V.I. Bokov A. van Remmen H. Mele J. Ran Q. Ikeno Y. Richardson A. Is the oxidative stress theory of aging dead? Biochim. Biophys. Acta 2009 1790 1005 1014 10.1016/j.bbagen.2009.06.003 19524016 PMC2789432 · DOI · Paper page
  51. [56]Muller F.L. Lustgarten M.S. Jang Y. Richardson A. van Remmen H. Trends in oxidative aging theories Free Radic. Biol. Med. 2007 43 477 503 10.1016/j.freeradbiomed.2007.03.034 17640558 · DOI · Paper page
  52. [57]Lebovitz R.M. Zhang H. Vogel H. Cartwright J. Jr. Dionne L. Lu N. Huang S. Matzuk M.M. Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice Proc. Natl. Acad. Sci. USA 1996 93 9782 9787 10.1073/pnas.93.18.9782 8790408 PMC38506 · DOI · Paper page
  53. [59]Jang Y.C. Remmen H.V. The mitochondrial theory of aging: Insight from transgenic and knockout mouse models Exp. Gerontol. 2009 44 256 260 10.1016/j.exger.2008.12.006 19171187 · DOI
  54. [60]Dai D.F. Chiao Y.A. Marcinek D.J. Szeto H.H. Rabinovitch P.S. Mitochondrial oxidative stress in aging and healthspan Longev. Healthspan 2014 3 6 10.1186/2046-2395-3-6 24860647 PMC4013820 · DOI
  55. [61]Hamilton R.T. Walsh M.E. van Remmen H. Mouse models of oxidative stress indicate a role for modulating healthy aging J. Clin. Exp. Pathol. 2012 10.4172/2161-0681.S4-005 25300955 PMC4188441 · DOI
  56. [62]Berry A. Cirulli F. The p66Shc gene paves the way for healthspan: Evolutionary and mechanistic perspectives Neurosci. Biobehav. Rev. 2013 37 790 802 10.1016/j.neubiorev.2013.03.005 23524280 · DOI
  57. [63]Wanagat J. Dai D.F. Rabinovitch P. Mitochondrial oxidative stress and mammalian healthspan Mech. Ageing Dev. 2010 131 527 535 10.1016/j.mad.2010.06.002 20566356 PMC2933331 · DOI
  58. [64]Sies H. Oxidative stress: A concept in redox biology and medicine Redox Biol. 2015 4 180 183 10.1016/j.redox.2015.01.002 25588755 PMC4309861 · DOI
  59. [65]Beckman J.S. Koppenol W.H. Nitric oxide, superoxide, and peroxynitrite: The good, the bad, and ugly Am. J. Physiol. 1996 271 C1424 C1437 8944624
  60. [66]Daiber A. Bachschmid M. Enzyme inhibition by peroxynitrite-mediated tyrosine nitration and thiol oxidation Curr. Enzym. Inhib. 2007 3 103 117 10.2174/157340807780598369 · DOI
  61. [67]Beckman J.S. Protein tyrosine nitration and peroxynitrite FASEB J. 2002 16 1144 10.1096/fj.02-0133lte 12087072 · DOI
  62. [68]Quijano C. Alvarez B. Gatti R.M. Augusto O. Radi R. Pathways of peroxynitrite oxidation of thiol groups Biochem. J. 1997 322 167 173 9078258 PMC1218173
  63. [69]MacMillan-Crow L.A. Crow J.P. Kerby J.D. Beckman J.S. Thompson J.A. Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts Proc. Natl. Acad. Sci. USA 1996 93 11853 11858 10.1073/pnas.93.21.11853 8876227 PMC38148 · DOI
  64. [71]Schulz E. Jansen T. Wenzel P. Daiber A. Munzel T. Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension Antioxid. Redox Signal. 2008 10 1115 1126 10.1089/ars.2007.1989 18321209 · DOI · Paper page
  65. [72]Yoshida Y.I. Eda S. Masada M. Alterations of tetrahydrobiopterin biosynthesis and pteridine levels in mouse tissues during growth and aging Brain Dev. 2000 22 S45 S49 10.1016/S0387-7604(00)00144-3 10984660 · DOI
  66. [73]Blackwell K.A. Sorenson J.P. Richardson D.M. Smith L.A. Suda O. Nath K. Katusic Z.S. Mechanisms of aging-induced impairment of endothelium-dependent relaxation: Role of tetrahydrobiopterin Am. J. Physiol. Heart Circ. Physiol. 2004 287 H2448 H2453 10.1152/ajpheart.00248.2004 15319209 · DOI
  67. [74]Chen C.A. Wang T.Y. Varadharaj S. Reyes L.A. Hemann C. Talukder M.A. Chen Y.R. Druhan L.J. Zweier J.L. S-glutathionylation uncouples eNOS and regulates its cellular and vascular function Nature 2010 468 1115 1118 10.1038/nature09599 21179168 PMC3370391 · DOI · Paper page
  68. [75]Schulz E. Wenzel P. Munzel T. Daiber A. Mitochondrial redox signaling: Interaction of mitochondrial reactive oxygen species with other sources of oxidative stress Antioxid. Redox Signal. 2014 20 308 324 10.1089/ars.2012.4609 22657349 PMC3887453 · DOI
  69. [78]Soucy K.G. Ryoo S. Benjo A. Lim H.K. Gupta G. Sohi J.S. Elser J. Aon M.A. Nyhan D. Shoukas A.A. Impaired shear stress-induced nitric oxide production through decreased NOS phosphorylation contributes to age-related vascular stiffness J. Appl. Physiol. 2006 101 1751 1759 10.1152/japplphysiol.00138.2006 17106067 · DOI · Paper page
  70. [80]Griendling K.K. Sorescu D. Ushio-Fukai M. NAD(P)H oxidase: Role in cardiovascular biology and disease Circ. Res. 2000 86 494 501 10.1161/01.RES.86.5.494 10720409 · DOI · Paper page
  71. [81]Paneni F. Osto E. Costantino S. Mateescu B. Briand S. Coppolino G. Perna E. Mocharla P. Akhmedov A. Kubant R. Deletion of the activated protein-1 transcription factor JunD induces oxidative stress and accelerates age-related endothelial dysfunction Circulation 2013 127 1229 1240 10.1161/CIRCULATIONAHA.112.000826 23410942 · DOI
  72. [83]Moe K.T. Aulia S. Jiang F. Chua Y.L. Koh T.H. Wong M.C. Dusting G.J. Differential upregulation of Nox homologues of NADPH oxidase by tumor necrosis factor-α in human aortic smooth muscle and embryonic kidney cells J. Cell. Mol. Med. 2006 10 231 239 10.1111/j.1582-4934.2006.tb00304.x 16563235 PMC3933115 · DOI
  73. [85]Nandi J. Saud B. Zinkievich J.M. Yang Z.J. Levine R.A. TNF-α modulates INOS expression in an experimental rat model of indomethacin-induced jejunoileitis Mol. Cell. Biochem. 2010 336 17 24 10.1007/s11010-009-0259-2 19802525 · DOI
  74. [86]Ungvari Z. Csiszar A. Edwards J.G. Kaminski P.M. Wolin M.S. Kaley G. Koller A. Increased superoxide production in coronary arteries in hyperhomocysteinemia: Role of tumor necrosis factor-α, NAD(P)H oxidase, and inducible nitric oxide synthase Arterioscler. Thromb. Vasc. Biol. 2003 23 418 424 10.1161/01.ATV.0000061735.85377.40 12615666 · DOI
  75. [87]Busik J.V. Mohr S. Grant M.B. Hyperglycemia-induced reactive oxygen species toxicity to endothelial cells is dependent on paracrine mediators Diabetes 2008 57 1952 1965 10.2337/db07-1520 18420487 PMC2453610 · DOI · Paper page
  76. [88]Csiszar A. Labinskyy N. Smith K. Rivera A. Orosz Z. Ungvari Z. Vasculoprotective effects of anti-tumor necrosis factor-α treatment in aging Am. J. Pathol. 2007 170 388 398 10.2353/ajpath.2007.060708 17200210 PMC1762698 · DOI
  77. [89]Ferrucci L. Corsi A. Lauretani F. Bandinelli S. Bartali B. Taub D.D. Guralnik J.M. Longo D.L. The origins of age-related proinflammatory state Blood 2005 105 2294 2299 10.1182/blood-2004-07-2599 15572589 PMC9828256 · DOI · Paper page
  78. [90]Wenzel P. Knorr M. Kossmann S. Stratmann J. Hausding M. Schuhmacher S. Karbach S.H. Schwenk M. Yogev N. Schulz E. Lysozyme M-positive monocytes mediate angiotensin II-induced arterial hypertension and vascular dysfunction Circulation 2011 124 1370 1381 10.1161/CIRCULATIONAHA.111.034470 21875910 · DOI
  79. [91]Guzik T.J. Hoch N.E. Brown K.A. McCann L.A. Rahman A. Dikalov S. Goronzy J. Weyand C. Harrison D.G. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction J. Exp. Med. 2007 204 2449 2460 10.1084/jem.20070657 17875676 PMC2118469 · DOI · Paper page
  80. [92]Harman D. The biologic clock: The mitochondria? J. Am. Geriatr. Soc. 1972 20 145 147 10.1111/j.1532-5415.1972.tb00787.x 5016631 · DOI
  81. [93]Lewis P. Stefanovic N. Pete J. Calkin A.C. Giunti S. Thallas-Bonke V. Jandeleit-Dahm K.A. Allen T.J. Kola I. Cooper M.E. Lack of the antioxidant enzyme glutathione peroxidase-1 accelerates atherosclerosis in diabetic apolipoprotein e-deficient mice Circulation 2007 115 2178 2187 10.1161/CIRCULATIONAHA.106.664250 17420349 · DOI
  82. [95]Chrissobolis S. Didion S.P. Kinzenbaw D.A. Schrader L.I. Dayal S. Lentz S.R. Faraci F.M. Glutathione peroxidase-1 plays a major role in protecting against angiotensin II-induced vascular dysfunction Hypertension 2008 51 872 877 10.1161/HYPERTENSIONAHA.107.103572 18299484 PMC3139513 · DOI
  83. [96]Blankenberg S. Rupprecht H.J. Bickel C. Torzewski M. Hafner G. Tiret L. Smieja M. Cambien F. Meyer J. Lackner K.J. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease N. Engl. J. Med. 2003 349 1605 1613 10.1056/NEJMoa030535 14573732 · DOI
  84. [97]Kroller-Schon S. Steven S. Kossmann S. Scholz A. Daub S. Oelze M. Xia N. Hausding M. Mikhed Y. Zinssius E. Molecular mechanisms of the crosstalk between mitochondria and NADPH oxidase through reactive oxygen species-studies in white blood cells and in animal models Antioxid. Redox Signal. 2014 20 247 266 10.1089/ars.2012.4953 23845067 PMC3887465 · DOI
  85. [98]Hausding M. Jurk K. Daub S. Kroller-Schon S. Stein J. Schwenk M. Oelze M. Mikhed Y. Kerahrodi J.G. Kossmann S. CD40L contributes to angiotensin II-induced pro-thrombotic state, vascular inflammation, oxidative stress and endothelial dysfunction Basic Res. Cardiol. 2013 108 386 10.1007/s00395-013-0386-5 24061433 · DOI
  86. [100]Lin M.I. Fulton D. Babbitt R. Fleming I. Busse R. Pritchard K.A. Jr. Sessa W.C. Phosphorylation of threonine 497 in endothelial nitric-oxide synthase coordinates the coupling of l-arginine metabolism to efficient nitric oxide production J. Biol. Chem. 2003 278 44719 44726 10.1074/jbc.M302836200 12952971 · DOI
  87. [101]Loot A.E. Schreiber J.G. Fisslthaler B. Fleming I. Angiotensin ii impairs endothelial function via tyrosine phosphorylation of the endothelial nitric oxide synthase J. Exp. Med. 2009 206 2889 2896 10.1084/jem.20090449 19934023 PMC2806451 · DOI
  88. [102]Brune B. Schmidt K.U. Ullrich V. Activation of soluble guanylate cyclase by carbon monoxide and inhibition by superoxide anion Eur. J. Biochem. 1990 192 683 688 10.1111/j.1432-1033.1990.tb19276.x 1976516 · DOI
  89. [103]Weber M. Lauer N. Mulsch A. Kojda G. The effect of peroxynitrite on the catalytic activity of soluble guanylyl cyclase Free Radic. Biol. Med. 2001 31 1360 1367 10.1016/S0891-5849(01)00706-7 11728807 · DOI
  90. [104]Artz J.D. Schmidt B. McCracken J.L. Marletta M.A. Effects of nitroglycerin on soluble guanylate cyclase: Implications for nitrate tolerance J. Biol. Chem. 2002 277 18253 18256 10.1074/jbc.C200170200 11937497 · DOI
  91. [105]Crassous P.A. Couloubaly S. Huang C. Zhou Z. Baskaran P. Kim D.D. Papapetropoulos A. Fioramonti X. Duran W.N. Beuve A. Soluble guanylyl cyclase is a target of angiotensin II-induced nitrosative stress in a hypertensive rat model Am. J. Physiol. Heart Circ. Physiol. 2012 303 H597 H604 10.1152/ajpheart.00138.2012 22730391 PMC3468472 · DOI
  92. [106]Mayer B. Kleschyov A.L. Stessel H. Russwurm M. Munzel T. Koesling D. Schmidt K. Inactivation of soluble guanylate cyclase by stoichiometric S-nitrosation Mol. Pharmacol. 2009 75 886 891 10.1124/mol.108.052142 19114587 · DOI
  93. [107]Sayed N. Kim D.D. Fioramonti X. Iwahashi T. Duran W.N. Beuve A. Nitroglycerin-induced S-nitrosylation and desensitization of soluble guanylyl cyclase contribute to nitrate tolerance Circ. Res. 2008 103 606 614 10.1161/CIRCRESAHA.108.175133 18669924 PMC2737267 · DOI · Paper page
  94. [108]Stasch J.P. Schmidt P.M. Nedvetsky P.I. Nedvetskaya T.Y. H S A.K. Meurer S. Deile M. Taye A. Knorr A. Lapp H. Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels J. Clin. Investig. 2006 116 2552 2561 10.1172/JCI28371 16955146 PMC1555649 · DOI
  95. [109]Chen L. Daum G. Fischer J.W. Hawkins S. Bochaton-Piallat M.L. Gabbiani G. Clowes A.W. Loss of expression of the β subunit of soluble guanylyl cyclase prevents nitric oxide-mediated inhibition of DNA synthesis in smooth muscle cells of old rats Circ. Res. 2000 86 520 525 10.1161/01.RES.86.5.520 10720413 · DOI
  96. [110]Ruetten H. Zabel U. Linz W. Schmidt H.H. Downregulation of soluble guanylyl cyclase in young and aging spontaneously hypertensive rats Circ. Res. 1999 85 534 541 10.1161/01.RES.85.6.534 10488056 · DOI
  97. [111]Kloss S. Bouloumie A. Mulsch A. Aging and chronic hypertension decrease expression of rat aortic soluble guanylyl cyclase Hypertension 2000 35 43 47 10642273
  98. [112]Lubos E. Mahoney C.E. Leopold J.A. Zhang Y.Y. Loscalzo J. Handy D.E. Glutathione peroxidase-1 modulates lipopolysaccharide-induced adhesion molecule expression in endothelial cells by altering CD14 expression FASEB J. 2010 24 2525 2532 10.1096/fj.09-147421 20219985 PMC2887263 · DOI
  99. [113]Kessler P. Bauersachs J. Busse R. Schini-Kerth V.B. Inhibition of inducible nitric oxide synthase restores endothelium-dependent relaxations in proinflammatory mediator-induced blood vessels Arterioscler. Thromb. Vasc. Biol. 1997 17 1746 1755 10.1161/01.ATV.17.9.1746 9327773 · DOI
  100. [114]Prabhu K.S. Zamamiri-Davis F. Stewart J.B. Thompson J.T. Sordillo L.M. Reddy C.C. Selenium deficiency increases the expression of inducible nitric oxide synthase in RAW 264.7 macrophages: Role of nuclear factor-κB in up-regulation Biochem. J. 2002 366 203 209 12006087 PMC1222757
  101. [115]Bulua A.C. Simon A. Maddipati R. Pelletier M. Park H. Kim K.Y. Sack M.N. Kastner D.L. Siegel R.M. Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS) J. Exp. Med. 2011 208 519 533 10.1084/jem.20102049 21282379 PMC3058571 · DOI · Paper page
  102. [116]West A.P. Brodsky I.E. Rahner C. Woo D.K. Erdjument-Bromage H. Tempst P. Walsh M.C. Choi Y. Shadel G.S. Ghosh S. TLR signalling augments macrophage bactericidal activity through mitochondrial ROS Nature 2011 472 476 480 10.1038/nature09973 21525932 PMC3460538 · DOI · Paper page
  103. [119]Smith A.R. Visioli F. Frei B. Hagen T.M. Age-related changes in endothelial nitric oxide synthase phosphorylation and nitric oxide dependent vasodilation: Evidence for a novel mechanism involving sphingomyelinase and ceramide-activated phosphatase 2A Aging Cell 2006 5 391 400 10.1111/j.1474-9726.2006.00232.x 16930126 · DOI
  104. [121]Schriner S.E. Linford N.J. Martin G.M. Treuting P. Ogburn C.E. Emond M. Coskun P.E. Ladiges W. Wolf N. van Remmen H. Extension of murine life span by overexpression of catalase targeted to mitochondria Science 2005 308 1909 1911 10.1126/science.1106653 15879174 · DOI · Paper page
  105. [122]Barja G. Herrero A. Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals FASEB J. 2000 14 312 318 10657987
  106. [123]Sastre J. Pallardo F.V. Vina J. The role of mitochondrial oxidative stress in aging Free Radic. Biol. Med. 2003 35 1 8 10.1016/S0891-5849(03)00184-9 12826250 · DOI
  107. [124]Madamanchi N.R. Runge M.S. Mitochondrial dysfunction in atherosclerosis Circ. Res. 2007 100 460 473 10.1161/01.RES.0000258450.44413.96 17332437 · DOI
  108. [125]De Souza-Pinto N.C. Eide L. Hogue B.A. Thybo T. Stevnsner T. Seeberg E. Klungland A. Bohr V.A. Repair of 8-oxodeoxyguanosine lesions in mitochondrial DNA depends on the oxoguanine DNA glycosylase (OGG1) gene and 8-oxoguanine accumulates in the mitochondrial dna of OGG1-defective mice Cancer Res. 2001 61 5378 5381 11454679
  109. [126]De Souza-Pinto N.C. Hogue B.A. Bohr V.A. DNA repair and aging in mouse liver: 8-oxodG glycosylase activity increase in mitochondrial but not in nuclear extracts Free Radic. Biol. Med. 2001 30 916 923 10.1016/S0891-5849(01)00483-X 11295534 · DOI
  110. [127]Souza-Pinto N.C. Croteau D.L. Hudson E.K. Hansford R.G. Bohr V.A. Age-associated increase in 8-oxo-deoxyguanosine glycosylase/ap lyase activity in rat mitochondria Nucleic Acids Res. 1999 27 1935 1942 10.1093/nar/27.8.1935 10101204 PMC148404 · DOI
  111. [129]Lewis W. Day B.J. Kohler J.J. Hosseini S.H. Chan S.S. Green E.C. Haase C.P. Keebaugh E.S. Long R. Ludaway T. Decreased mtDNA, oxidative stress, cardiomyopathy, and death from transgenic cardiac targeted human mutant polymerase γ Lab. Investig. 2007 87 326 335 17310215 PMC1831462
  112. [130]Finsterer J. Overview on visceral manifestations of mitochondrial disorders Neth. J. Med. 2006 64 61 71 16547358
  113. [131]Anan R. Nakagawa M. Miyata M. Higuchi I. Nakao S. Suehara M. Osame M. Tanaka H. Cardiac involvement in mitochondrial diseases. A study on 17 patients with documented mitochondrial DNA defects Circulation 1995 91 955 961 10.1161/01.CIR.91.4.955 7850981 · DOI
  114. [132]Pinsky D.J. Oz M.C. Koga S. Taha Z. Broekman M.J. Marcus A.J. Liao H. Naka Y. Brett J. Cannon P.J. Cardiac preservation is enhanced in a heterotopic rat transplant model by supplementing the nitric oxide pathway J. Clin. Investig. 1994 93 2291 2297 10.1172/JCI117230 7514195 PMC294392 · DOI
  115. [133]Zeviani M. di Donato S. Mitochondrial disorders Brain 2004 127 2153 2172 10.1093/brain/awh259 15358637 · DOI
  116. [134]Ballinger S.W. Patterson C. Knight-Lozano C.A. Burow D.L. Conklin C.A. Hu Z. Reuf J. Horaist C. Lebovitz R. Hunter G.C. Mitochondrial integrity and function in atherogenesis Circulation 2002 106 544 549 10.1161/01.CIR.0000023921.93743.89 12147534 · DOI
  117. [135]Sevini F. Giuliani C. Vianello D. Giampieri E. Santoro A. Biondi F. Garagnani P. Passarino G. Luiselli D. Capri M. mtDNA mutations in human aging and longevity: Controversies and new perspectives opened by high-throughput technologies Exp.Gerontol. 2014 56 234 244 10.1016/j.exger.2014.03.022 24709341 · DOI · Paper page
  118. [137]Larsson N.G. Somatic mitochondrial DNA mutations in mammalian aging Annu. Rev. Biochem. 2010 79 683 706 10.1146/annurev-biochem-060408-093701 20350166 · DOI
  119. [138]De Bont R. van Larebeke N. Endogenous DNA damage in humans: A review of quantitative data Mutagenesis 2004 19 169 185 10.1093/mutage/geh025 15123782 · DOI
  120. [139]Kennedy S.R. Salk J.J. Schmitt M.W. Loeb L.A. Ultra-sensitive sequencing reveals an age-related increase in somatic mitochondrial mutations that are inconsistent with oxidative damage PLoS Genet. 2013 9 e1003794 10.1371/journal.pgen.1003794 24086148 PMC3784509 · DOI · Paper page
  121. [140]Cha M.Y. Kim D.K. Mook-Jung I. The role of mitochondrial DNA mutation on neurodegenerative diseases Exp. Mol. Med. 2015 47 e150 10.1038/emm.2014.122 25766619 PMC4351410 · DOI
  122. [141]Reddy P.H. Amyloid β, mitochondrial structural and functional dynamics in alzheimer’s disease Exp. Neurol. 2009 218 286 292 10.1016/j.expneurol.2009.03.042 19358844 PMC2710427 · DOI
  123. [142]Canugovi C. Shamanna R.A. Croteau D.L. Bohr V.A. Base excision DNA repair levels in mitochondrial lysates of alzheimer’s disease Neurobiol. Aging 2014 35 1293 1300 10.1016/j.neurobiolaging.2014.01.004 24485507 PMC5576885 · DOI
  124. [143]Krishnan K.J. Ratnaike T.E. de Gruyter H.L. Jaros E. Turnbull D.M. Mitochondrial DNA deletions cause the biochemical defect observed in alzheimer’s disease Neurobiol. Aging 2012 33 2210 2214 10.1016/j.neurobiolaging.2011.08.009 21925769 · DOI · Paper page
  125. [144]Muftuoglu M. Mori M.P. de Souza-Pinto N.C. Formation and repair of oxidative damage in the mitochondrial DNA Mitochondrion 2014 17 164 181 10.1016/j.mito.2014.03.007 24704805 · DOI
  126. [145]Liu P. Demple B. DNA repair in mammalian mitochondria: Much more than we thought? Environ. Mol. Mutagen. 2010 51 417 426 10.1002/em.20576 20544882 · DOI
  127. [146]Bogenhagen D.F. Repair of mtDNA in vertebrates Am. J. Hum. Genet. 1999 64 1276 1281 10.1086/302392 10205257 PMC1377862 · DOI
  128. [147]Nishioka K. Ohtsubo T. Oda H. Fujiwara T. Kang D. Sugimachi K. Nakabeppu Y. Expression and differential intracellular localization of two major forms of human 8-oxoguanine DNA glycosylase encoded by alternatively spliced OGG1 mRNAs Mol. Biol. Cell 1999 10 1637 1652 10.1091/mbc.10.5.1637 10233168 PMC30487 · DOI
  129. [148]Nilsen H. Otterlei M. Haug T. Solum K. Nagelhus T.A. Skorpen F. Krokan H.E. Nuclear and mitochondrial uracil-DNA glycosylases are generated by alternative splicing and transcription from different positions in the UNG gene Nucleic Acids Res. 1997 25 750 755 10.1093/nar/25.4.750 9016624 PMC146498 · DOI
  130. [149]Ikeda S. Kohmoto T. Tabata R. Seki Y. Differential intracellular localization of the human and mouse endonuclease III homologs and analysis of the sorting signals DNA Repair 2002 1 847 854 10.1016/S1568-7864(02)00145-3 12531031 · DOI
  131. [150]Hu J. de Souza-Pinto N.C. Haraguchi K. Hogue B.A. Jaruga P. Greenberg M.M. Dizdaroglu M. Bohr V.A. Repair of formamidopyrimidines in DNA involves different glycosylases: Role of the OGG1, NTH1, and NEIL1 enzymes J. Biol. Chem. 2005 280 40544 40551 10.1074/jbc.M508772200 16221681 · DOI
  132. [151]Ohtsubo T. Nishioka K. Imaiso Y. Iwai S. Shimokawa H. Oda H. Fujiwara T. Nakabeppu Y. Identification of human muty homolog (hMYH) as a repair enzyme for 2-hydroxyadenine in DNA and detection of multiple forms of hMYH located in nuclei and mitochondria Nucleic Acids Res. 2000 28 1355 1364 10.1093/nar/28.6.1355 10684930 PMC111038 · DOI
  133. [152]Park J.S. Kim H.L. Kim Y.J. Weon J.I. Sung M.K. Chung H.W. Seo Y.R. Human AP endonuclease 1: A potential marker for the prediction of environmental carcinogenesis risk Oxidative Med. Cell. Longev. 2014 2014 730301 10.1155/2014/730301 25243052 PMC4158471 · DOI
  134. [153]Mason P.A. Matheson E.C. Hall A.G. Lightowlers R.N. Mismatch repair activity in mammalian mitochondria Nucleic Acids Res. 2003 31 1052 1058 10.1093/nar/gkg167 12560503 PMC149189 · DOI
  135. [154]De Souza-Pinto N.C. Mason P.A. Hashiguchi K. Weissman L. Tian J. Guay D. Lebel M. Stevnsner T.V. Rasmussen L.J. Bohr V.A. Novel DNA mismatch-repair activity involving YB-1 in human mitochondria DNA Repair 2009 8 704 719 10.1016/j.dnarep.2009.01.021 19272840 PMC2693314 · DOI · Paper page
  136. [156]Chen X.J. Mechanism of homologous recombination and implications for aging-related deletions in mitochondrial DNA Microbiol. Mol. Biol. Rev. 2013 77 476 496 10.1128/MMBR.00007-13 24006472 PMC3811608 · DOI
  137. [157]Chen X.J. Guan M.X. Clark-Walker G.D. MGM101, a nuclear gene involved in maintenance of the mitochondrial genome in saccharomyces cerevisiae Nucleic Acids Res. 1993 21 3473 3477 10.1093/nar/21.15.3473 8346025 PMC331447 · DOI
  138. [158]Gredilla R. Garm C. Stevnsner T. Nuclear and mitochondrial DNA repair in selected eukaryotic aging model systems Oxidative Med. Cell. Longev. 2012 2012 282438 10.1155/2012/282438 23050036 PMC3462412 · DOI
  139. [159]Bender A. Krishnan K.J. Morris C.M. Taylor G.A. Reeve A.K. Perry R.H. Jaros E. Hersheson J.S. Betts J. Klopstock T. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease Nat. Genet. 2006 38 515 517 10.1038/ng1769 16604074 · DOI · Paper page
  140. [160]Chen D. Cao G. Hastings T. Feng Y. Pei W. O’Horo C. Chen J. Age-dependent decline of DNA repair activity for oxidative lesions in rat brain mitochondria J. Neurochem. 2002 81 1273 1284 10.1046/j.1471-4159.2002.00916.x 12068075 · DOI
  141. [161]Daiber A. Oelze M. Wenzel P. Wickramanayake J.M. Schuhmacher S. Jansen T. Lackner K.J. Torzewski M. Munzel T. Nitrate tolerance as a model of vascular dysfunction: Roles for mitochondrial aldehyde dehydrogenase and mitochondrial oxidative stress Pharmacol. Rep. 2009 61 33 48 10.1016/S1734-1140(09)70005-2 19307691 · DOI
  142. [162]Daiber A. Oelze M. Coldewey M. Bachschmid M. Wenzel P. Sydow K. Wendt M. Kleschyov A.L. Stalleicken D. Ullrich V. Oxidative stress and mitochondrial aldehyde dehydrogenase activity: A comparison of pentaerythritol tetranitrate with other organic nitrates Mol. Pharmacol. 2004 66 1372 1382 10.1124/mol.104.002600 15331769 · DOI · Paper page
  143. [164]Esplugues J.V. Rocha M. Nunez C. Bosca I. Ibiza S. Herance J.R. Ortega A. Serrador J.M. D’Ocon P. Victor V.M. Complex I dysfunction and tolerance to nitroglycerin: An approach based on mitochondrial-targeted antioxidants Circ. Res. 2006 99 1067 1075 10.1161/01.RES.0000250430.62775.99 17053193 · DOI
  144. [165]Wenzel P. Mollnau H. Oelze M. Schulz E. Wickramanayake J.M. Muller J. Schuhmacher S. Hortmann M. Baldus S. Gori T. First evidence for a crosstalk between mitochondrial and nadph oxidase-derived reactive oxygen species in nitroglycerin-triggered vascular dysfunction Antioxid. Redox Signal. 2008 10 1435 1447 10.1089/ars.2007.1969 18522491 · DOI
  145. [166]Dikalov S.I. Nazarewicz R.R. Bikineyeva A. Hilenski L. Lassegue B. Griendling K.K. Harrison D.G. Dikalova A.E. Nox2-induced production of mitochondrial superoxide in angiotensin II-mediated endothelial oxidative stress and hypertension Antioxid. Redox Signal. 2014 20 281 294 10.1089/ars.2012.4918 24053613 PMC3887459 · DOI
  146. [168]Nazarewicz R.R. Dikalova A.E. Bikineyeva A. Dikalov S.I. Nox2 as a potential target of mitochondrial superoxide and its role in endothelial oxidative stress Am. J. Physiol. Heart Circ. Physiol. 2013 305 H1131 H1140 10.1152/ajpheart.00063.2013 23955717 PMC3798790 · DOI
  147. [169]Brandes R.P. Triggering mitochondrial radical release: A new function for NADPH oxidases Hypertension 2005 45 847 848 10.1161/01.HYP.0000165019.32059.b2 15837827 · DOI · Paper page
  148. [170]Kimura S. Zhang G.X. Nishiyama A. Shokoji T. Yao L. Fan Y.Y. Rahman M. Abe Y. Mitochondria-derived reactive oxygen species and vascular MAP kinases: Comparison of angiotensin II and diazoxide Hypertension 2005 45 438 444 10.1161/01.HYP.0000157169.27818.ae 15699441 · DOI
  149. [171]Dikalova A.E. Bikineyeva A.T. Budzyn K. Nazarewicz R.R. McCann L. Lewis W. Harrison D.G. Dikalov S.I. Therapeutic targeting of mitochondrial superoxide in hypertension Circ. Res. 2010 107 106 116 10.1161/CIRCRESAHA.109.214601 20448215 PMC2901409 · DOI
  150. [172]Fukui T. Ishizaka N. Rajagopalan S. Laursen J.B. Capers Q.T. Taylor W.R. Harrison D.G. de Leon H. Wilcox J.N. Griendling K.K. p22phox mRNA expression and NADPH oxidase activity are increased in aortas from hypertensive rats Circ. Res. 1997 80 45 51 10.1161/01.RES.80.1.45 8978321 · DOI · Paper page
  151. [173]Cheresh P. Kim S.J. Tulasiram S. Kamp D.W. Oxidative stress and pulmonary fibrosis Biochim. Biophys. Acta 2013 1832 1028 1040 10.1016/j.bbadis.2012.11.021 23219955 PMC3639303 · DOI
  152. [174]Nazarewicz R.R. Dikalov S.I. Mitochondrial ROS in the prohypertensive immune response Am. J. Physiol. Regul. Integr. Comp. Physiol. 2013 305 R98 R100 10.1152/ajpregu.00208.2013 23657641 PMC3726999 · DOI
  153. [175]Bender A. Hajieva P. Moosmann B. Adaptive antioxidant methionine accumulation in respiratory chain complexes explains the use of a deviant genetic code in mitochondria Proc. Natl. Acad. Sci. USA 2008 105 16496 16501 10.1073/pnas.0802779105 18946048 PMC2575448 · DOI
  154. [176]Moskovitz J. Bar-Noy S. Williams W.M. Requena J. Berlett B.S. Stadtman E.R. Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals Proc. Natl. Acad. Sci. USA 2001 98 12920 12925 10.1073/pnas.231472998 11606777 PMC60800 · DOI
  155. [177]Stadtman E.R. Moskovitz J. Berlett B.S. Levine R.L. Cyclic oxidation and reduction of protein methionine residues is an important antioxidant mechanism Mol. Cell. Biochem. 2002 234–235 3 9 10.1023/A:1015916831583 12162447 · DOI
  156. [178]Taungjaruwinai W.M. Bhawan J. Keady M. Thiele J.J. Differential expression of the antioxidant repair enzyme methionine sulfoxide reductase (MSRA and MSRB) in human skin Am. J. Dermatopathol. 2009 31 427 431 10.1097/DAD.0b013e3181882c21 19542914 · DOI
  157. [179]Mochin M.T. Underwood K.F. Cooper B. McLenithan J.C. Pierce A.D. Nalvarte C. Arbiser J. Karlsson A.I. Moise A.R. Moskovitz J. Hyperglycemia and redox status regulate RUNX2 DNA-binding and an angiogenic phenotype in endothelial cells Microvasc. Res. 2015 97 55 64 10.1016/j.mvr.2014.09.008 25283348 PMC4412363 · DOI
  158. [180]Gu H. Chen W. Yin J. Chen S. Zhang J. Gong J. Methionine sulfoxide reductase A rs10903323 G/A polymorphism is associated with increased risk of coronary artery disease in a chinese population Clin. Biochem. 2013 46 1668 1672 10.1016/j.clinbiochem.2013.07.011 23880405 · DOI
  159. [181]Haenold R. Wassef R. Brot N. Neugebauer S. Leipold E. Heinemann S.H. Hoshi T. Protection of vascular smooth muscle cells by over-expressed methionine sulphoxide reductase A: Role of intracellular localization and substrate availability Free Radic. Res. 2008 42 978 988 10.1080/10715760802566541 19085252 · DOI
  160. [182]Moosmann B. Behl C. Mitochondrially encoded cysteine predicts animal lifespan Aging Cell 2008 7 32 46 10.1111/j.1474-9726.2007.00349.x 18028257 · DOI
  161. [183]Camici G.G. Cosentino F. Tanner F.C. Luscher T.F. The role of p66Shc deletion in age-associated arterial dysfunction and disease states J. Appl. Physiol. 2008 105 1628 1631 10.1152/japplphysiol.90579.2008 18772327 · DOI
  162. [185]Gertz M. Fischer F. Wolters D. Steegborn C. Activation of the lifespan regulator p66Shc through reversible disulfide bond formation Proc. Natl. Acad. Sci. USA 2008 105 5705 5709 10.1073/pnas.0800691105 18413607 PMC2311372 · DOI
  163. [186]Pinton P. Rimessi A. Marchi S. Orsini F. Migliaccio E. Giorgio M. Contursi C. Minucci S. Mantovani F. Wieckowski M.R. Protein kinase C β and prolyl isomerase 1 regulate mitochondrial effects of the life-span determinant p66Shc Science 2007 315 659 663 10.1126/science.1135380 17272725 · DOI
  164. [187]Pinton P. Rizzuto R. P66Shc, oxidative stress and aging: Importing a lifespan determinant into mitochondria Cell. Cycle 2008 7 304 308 10.4161/cc.7.3.5360 18235239 PMC2696632 · DOI
  165. [189]Yamamori T. White A.R. Mattagajasingh I. Khanday F.A. Haile A. Qi B. Jeon B.H. Bugayenko A. Kasuno K. Berkowitz D.E. p66Shc regulates endothelial no production and endothelium-dependent vasorelaxation: Implications for age-associated vascular dysfunction J. Mol. Cell. Cardiol. 2005 39 992 995 10.1016/j.yjmcc.2005.09.003 16242150 · DOI
  166. [190]Trinei M. Giorgio M. Cicalese A. Barozzi S. Ventura A. Migliaccio E. Milia E. Padura I.M. Raker V.A. Maccarana M. A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis Oncogene 2002 21 3872 3878 10.1038/sj.onc.1205513 12032825 · DOI · Paper page
  167. [191]Di Lisa F. Kaludercic N. Carpi A. Menabo R. Giorgio M. Mitochondrial pathways for ROS formation and myocardial injury: The relevance of p66Shc and monoamine oxidase Basic Res. Cardiol. 2009 104 131 139 10.1007/s00395-009-0008-4 19242637 · DOI
  168. [192]Spescha R.D. Klohs J. Semerano A. Giacalone G. Derungs R.S. Reiner M.F. Rodriguez Gutierrez D. Mendez-Carmona N. Glanzmann M. Savarese G. Post-ischaemic silencing of p66Shc reduces ischaemia/reperfusion brain injury and its expression correlates to clinical outcome in stroke Eur. Heart J. 2015 36 1590 1600 10.1093/eurheartj/ehv140 25904764 · DOI
  169. [193]Moskalev A.A. Aliper A.M. Smit-McBride Z. Buzdin A. Zhavoronkov A. Genetics and epigenetics of aging and longevity Cell. Cycle 2014 13 1063 1077 10.4161/cc.28433 24603410 PMC4013158 · DOI
  170. [194]Barbot W. Dupressoir A. Lazar V. Heidmann T. Epigenetic regulation of an IAP retrotransposon in the aging mouse: Progressive demethylation and de-silencing of the element by its repetitive induction Nucleic Acids Res. 2002 30 2365 2373 10.1093/nar/30.11.2365 12034823 PMC117196 · DOI
  171. [196]Tsurumi A. Li W.X. Global heterochromatin loss: A unifying theory of aging? Epigenetics 2012 7 680 688 10.4161/epi.20540 22647267 PMC3414389 · DOI
  172. [198]Bilsland A.E. Revie J. Keith W. Microrna and senescence: The senectome, integration and distributed control Crit. Rev. Oncog. 2013 18 373 390 10.1615/CritRevOncog.2013007197 23614622 · DOI
  173. [199]Boon R.A. Iekushi K. Lechner S. Seeger T. Fischer A. Heydt S. Kaluza D. Treguer K. Carmona G. Bonauer A. MicroRNA-34a regulates cardiac ageing and function Nature 2013 495 107 110 10.1038/nature11919 23426265 · DOI · Paper page
  174. [200]Guarner V. Rubio-Ruiz M.E. Low-grade systemic inflammation connects aging, metabolic syndrome and cardiovascular disease Interdiscip. Top. Gerontol. 2015 40 99 106 25341516
  175. [201]Howcroft T.K. Campisi J. Louis G.B. Smith M.T. Wise B. Wyss-Coray T. Augustine A.D. McElhaney J.E. Kohanski R. Sierra F. The role of inflammation in age-related disease Aging 2013 5 84 93 23474627 PMC3616233
  176. [203]Wilson P.W. Established risk factors and coronary artery disease: The framingham study Am. J. Hypertens. 1994 7 7S 12S 7946184
  177. [204]Munzel T. Sinning C. Post F. Warnholtz A. Schulz E. Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction Ann. Med. 2008 40 180 196 10.1080/07853890701854702 18382884 · DOI
  178. [206]Schachinger V. Britten M.B. Zeiher A.M. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease Circulation 2000 101 1899 1906 10.1161/01.CIR.101.16.1899 10779454 · DOI
  179. [207]Gori T. Munzel T. Oxidative stress and endothelial dysfunction: Therapeutic implications Ann. Med. 2011 43 259 272 10.3109/07853890.2010.543920 21284528 · DOI
  180. [208]Chen A.F. Chen D.D. Daiber A. Faraci F.M. Li H. Rembold C.M. Laher I. Free radical biology of the cardiovascular system Clin. Sci. 2012 123 73 91 10.1042/CS20110562 22455351 · DOI
  181. [209]Kimura Y. Matsumoto M. Den Y.B. Iwai K. Munehira J. Hattori H. Hoshino T. Yamada K. Kawanishi K. Tsuchiya H. Impaired endothelial function in hypertensive elderly patients evaluated by high resolution ultrasonography Can. J. Cardiol. 1999 15 563 568 10350666
  182. [210]Wray D.W. Nishiyama S.K. Harris R.A. Zhao J. McDaniel J. Fjeldstad A.S. Witman M.A. Ives S.J. Barrett-O’Keefe Z. Richardson R.S. Acute reversal of endothelial dysfunction in the elderly after antioxidant consumption Hypertension 2012 59 818 824 10.1161/HYPERTENSIONAHA.111.189456 22353612 PMC3321727 · DOI
  183. [211]Jousilahti P. Vartiainen E. Tuomilehto J. Puska P. Sex, age, cardiovascular risk factors, and coronary heart disease: A prospective follow-up study of 14 786 middle-aged men and women in Finland Circulation 1999 99 1165 1172 10.1161/01.CIR.99.9.1165 10069784 · DOI · Paper page
  184. [212]Holzer M. Trieb M. Konya V. Wadsack C. Heinemann A. Marsche G. Aging affects high-density lipoprotein composition and function Biochim. Biophys. Acta 2013 1831 1442 1448 10.1016/j.bbalip.2013.06.004 23792422 PMC3787738 · DOI
  185. [213]Besler C. Heinrich K. Riwanto M. Luscher T.F. Landmesser U. High-density lipoprotein-mediated anti-atherosclerotic and endothelial-protective effects: A potential novel therapeutic target in cardiovascular disease Curr. Pharm. Des. 2010 16 1480 1493 10.2174/138161210791051013 20196740 · DOI
  186. [214]Wu Z. Siuda D. Xia N. Reifenberg G. Daiber A. Munzel T. Forstermann U. Li H. Maternal treatment of spontaneously hypertensive rats with pentaerythritol tetranitrate reduces blood pressure in female offspring Hypertension 2015 65 232 237 10.1161/HYPERTENSIONAHA.114.04416 25385760 · DOI
  187. [216]Klipstein-Grobusch K. Geleijnse J.M. den Breeijen J.H. Boeing H. Hofman A. Grobbee D.E. Witteman J.C. Dietary antioxidants and risk of myocardial infarction in the elderly: The rotterdam study Am. J. Clin. Nutr. 1999 69 261 266 9989690

Cited by

Sorted by citations

Authors
Mikhed, Y., Daiber, A., & Steven, S.
Affiliations
Johannes Gutenberg University Mainz (DE)
Corresponding author
Daiber, Andreas
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2015-07-13
Volume
16
Issue
7
Pages
15918-15953
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms160715918
PMC
PMC4519931
OpenAlex
W1509805561
Cited by
257
References
29
Citations by year
2026: 17 · 2025: 24 · 2024: 20 · 2023: 24 · 2022: 17 · 2021: 22 · 2020: 26 · 2019: 21 · 2018: 25 · 2017: 27 · 2016: 27 · 2015: 6
FWCI
3.48
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • European Society of Cardiology
  • Bundesministerium für Bildung und Forschung (BMBF 01EO1003, 01EO1003)
  • Boehringer Ingelheim Stiftung
  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Keywords
mitochondrial oxidative stress, mitochondrial DNA damage, vascular aging, endothelial dysfunction, reactive oxygen species, mitochondrial reactive oxygen species, NADPH oxidase, nitric oxide signaling, low-grade inflammation, healthy aging
MeSH terms
Aging, Animals, Antioxidants, Cardiovascular Diseases, DNA Damage, DNA Repair, DNA, Mitochondrial, Humans, Mitochondria, Reactive Oxygen Species, Oxidative Stress

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