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

Kelly, 1997, Paul dudley white international lecture. Our future society. A global challenge, Circulation, 95, 2459, 10.1161/01.CIR.95.11.2459

Lakatta, 2003, Arterial and cardiac aging: Major shareholders in cardiovascular disease enterprises: Part I: Aging arteries: A “set up” for vascular disease, Circulation, 107, 139, 10.1161/01.CIR.0000048892.83521.58

Ras, 2013, Flow-mediated dilation and cardiovascular risk prediction: A systematic review with meta-analysis, Int. J. Cardiol., 168, 344, 10.1016/j.ijcard.2012.09.047

Herrera, 2010, Endothelial dysfunction and aging: An update, Ageing Res. Rev., 9, 142, 10.1016/j.arr.2009.07.002

Bischoff, 2006, Inadequate medical treatment of patients with coronary artery disease by primary care physicians in germany, Clin. Res. Cardiol., 95, 405, 10.1007/s00392-006-0399-2

Burnett, 2006, The role of nitric oxide in erectile dysfunction: Implications for medical therapy, J. Clin. Hypertens., 8, 53, 10.1111/j.1524-6175.2006.06026.x

Csiszar, 2007, The aging kidney: Role of endothelial oxidative stress and inflammation, Acta Physiol. Hung., 94, 107, 10.1556/APhysiol.94.2007.1-2.10

Price, 2004, Aging enhances vascular dysfunction induced by the alzheimer’s peptide β-amyloid, Neurol. Res., 26, 305, 10.1179/016164104225014003

Coleman, 2008, Age-related macular degeneration, Lancet, 372, 1835, 10.1016/S0140-6736(08)61759-6

Angulo, 2013, Oxidative stress and vascular inflammation in aging, Free Radic. Biol. Med., 65, 380, 10.1016/j.freeradbiomed.2013.07.003

Cesari, 2006, Comorbidity and physical function: Results from the aging and longevity study in the Sirente geographic area (iLSIRENTE study), Gerontology, 52, 24, 10.1159/000089822

Yancik, 2007, Report of the national institute on aging task force on comorbidity, J. Gerontol. Ser. A, 62, 275, 10.1093/gerona/62.3.275

Wieland, 2005, From bedside to bench: Research in comorbidity and aging, Sci. Aging Knowl. Environ., 2005, pe29, 10.1126/sageke.2005.39.pe29

Munzel, 2005, Explaining the phenomenon of nitrate tolerance, Circ. Res., 97, 618, 10.1161/01.RES.0000184694.03262.6d

Munzel, 2005, 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., 25, 1551, 10.1161/01.ATV.0000168896.64927.bb

Oelze, 2014, Glutathione peroxidase-1 deficiency potentiates dysregulatory modifications of endothelial nitric oxide synthase and vascular dysfunction in aging, Hypertension, 63, 390, 10.1161/HYPERTENSIONAHA.113.01602

Labugger, 2000, Enhanced peroxynitrite formation is associated with vascular aging, J. Exp. Med., 192, 1731, 10.1084/jem.192.12.1731

Forstermann, 2012, Nitric oxide synthases: Regulation and function, Eur. Heart J., 33, 829, 10.1093/eurheartj/ehr304

Laher, I. (2014). Systems Biology of Free Radicals and Antioxidants, Springer-Verlag.

Donato, 2009, Vascular endothelial dysfunction with aging: Endothelin-1 and endothelial nitric oxide synthase, Am. J. Phys. Heart Circ. Physiol., 297, H425, 10.1152/ajpheart.00689.2008

Donato, 2011, SIRT-1 and vascular endothelial dysfunction with ageing in mice and humans, J. Physiol., 589, 4545, 10.1113/jphysiol.2011.211219

Higashi, 2006, Tetrahydrobiopterin improves aging-related impairment of endothelium-dependent vasodilation through increase in nitric oxide production, Atherosclerosis, 186, 390, 10.1016/j.atherosclerosis.2005.07.025

Wenzel, 2008, Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction, Cardiovasc. Res., 80, 280, 10.1093/cvr/cvn182

Gerhard, 1996, Aging progressively impairs endothelium-dependent vasodilation in forearm resistance vessels of humans, Hypertension, 27, 849, 10.1161/01.HYP.27.4.849

Heitzer, 2001, Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease, Circulation, 104, 2673, 10.1161/hc4601.099485

Savji, 2013, Association between advanced age and vascular disease in different arterial territories: A population database of over 3.6 million subjects, J. Am. Coll. Cardiol., 61, 1736, 10.1016/j.jacc.2013.01.054

Ong, 2007, Prevalence, awareness, treatment, and control of hypertension among united states adults 1999–2004, Hypertension, 49, 69, 10.1161/01.HYP.0000252676.46043.18

Bondy, S.C., and Maiese, K. (2010). Aging and Age-Related Disorders, Humana Press.

Cadenas, 2000, Mitochondrial free radical generation, oxidative stress, and aging, Free Radic. Biol. Med., 29, 222, 10.1016/S0891-5849(00)00317-8

Lenaz, 2002, Role of mitochondria in oxidative stress and aging, Ann. N. Y. Acad. Sci., 959, 199, 10.1111/j.1749-6632.2002.tb02094.x

Kujoth, 2005, Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging, Science, 309, 481, 10.1126/science.1112125

Yin, 2014, Mitochondrial energy metabolism and redox signaling in brain aging and neurodegeneration, Antioxid. Redox Signal., 20, 353, 10.1089/ars.2012.4774

Cheng, 2005, Angiotensin II and vascular inflammation, Med. Sci. Monit., 11, RA194

Lau, 2006, Myeloperoxidase and its contributory role in inflammatory vascular disease, Pharmacol. Ther., 111, 16, 10.1016/j.pharmthera.2005.06.023

Willerson, 1989, Specific platelet mediators and unstable coronary artery lesions. Experimental evidence and potential clinical implications, Circulation, 80, 198, 10.1161/01.CIR.80.1.198

Seals, 2011, Aging and vascular endothelial function in humans, Clin. Sci., 120, 357, 10.1042/CS20100476

Tanaka, 2000, Age-related increase in femoral intima-media thickness in healthy humans, Arterioscler. Thromb. Vasc. Biol., 20, 2172, 10.1161/01.ATV.20.9.2172

Crimi, 2007, Microcirculation and oxidative stress, Free Radic. Res., 41, 1364, 10.1080/10715760701732830

Mayhan, 2008, Age-related alterations in reactivity of cerebral arterioles: Role of oxidative stress, Microcirculation, 15, 225, 10.1080/10739680701641421

Militante, 2004, Age-related retinal degeneration in animal models of aging: Possible involvement of taurine deficiency and oxidative stress, Neurochem. Res., 29, 151, 10.1023/B:NERE.0000010444.97959.1b

Fischer, 2015, Interrelation of oxidative stress and inflammation in neurodegenerative disease: Role of TNF, Oxidative Med. Cell. Longev., 2015, 610813, 10.1155/2015/610813

Blasiak, 2014, Oxidative stress, hypoxia, and autophagy in the neovascular processes of age-related macular degeneration, BioMed. Res. Int., 2014, 768026, 10.1155/2014/768026

Harman, 1956, Aging: A theory based on free radical and radiation chemistry, J. Gerontol., 11, 298, 10.1093/geronj/11.3.298

Waters, W.A. (1946). Some recent developments in the chemistry of free radicals. J. Chem. Soc., 409–415.

Rogell, 2014, Mito-nuclear interactions as drivers of gene movement on and off the X-chromosome, BMC Genomics, 15, 330, 10.1186/1471-2164-15-330

Thomas, 2008, The chemical biology of nitric oxide: Implications in cellular signaling, Free Radic. Biol. Med., 45, 18, 10.1016/j.freeradbiomed.2008.03.020

Bachschmid, 2006, Age-associated cellular relocation of Sod 1 as a self-defense is a futile mechanism to prevent vascular aging, Biochem. Biophys. Res. Commun., 344, 972, 10.1016/j.bbrc.2006.03.224

Bladier, 2004, Fibroblasts derived from Gpx1 knockout mice display senescent-like features and are susceptible to H2O2-mediated cell death, Free Radic. Biol. Med., 36, 53, 10.1016/j.freeradbiomed.2003.10.020

Altschmied, 2009, Thioredoxin-1 and endothelial cell aging: Role in cardiovascular diseases, Antioxid. Redox Signal., 11, 1733, 10.1089/ars.2008.2379

Go, 2010, Redox control systems in the nucleus: Mechanisms and functions, Antioxid. Redox Signal., 13, 489, 10.1089/ars.2009.3021

Salmon, 2010, Update on the oxidative stress theory of aging: Does oxidative stress play a role in aging or healthy aging?, Free Radic. Biol. Med., 48, 642, 10.1016/j.freeradbiomed.2009.12.015

Brown, 2007, Effect of aging, MnSOD deficiency, and genetic background on endothelial function: Evidence for MnSOD haploinsufficiency, Arterioscler. Thromb. Vasc. Biol., 27, 1941, 10.1161/ATVBAHA.107.146852

Didion, 2006, Heterozygous CuZn superoxide dismutase deficiency produces a vascular phenotype with aging, Hypertension, 48, 1072, 10.1161/01.HYP.0000247302.20559.3a

Goldstein, 2000, Tyrosine nitration by simultaneous generation of •NO and O•2 under physiological conditions. How the radicals do the job, J. Biol. Chem., 275, 3031, 10.1074/jbc.275.5.3031

Perez, 2009, Is the oxidative stress theory of aging dead?, Biochim. Biophys. Acta, 1790, 1005, 10.1016/j.bbagen.2009.06.003

Muller, 2007, Trends in oxidative aging theories, Free Radic. Biol. Med., 43, 477, 10.1016/j.freeradbiomed.2007.03.034

Lebovitz, 1996, Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice, Proc. Natl. Acad. Sci. USA, 93, 9782, 10.1073/pnas.93.18.9782

Li, 1995, Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase, Nat. Genet., 11, 376, 10.1038/ng1295-376

Jang, 2009, The mitochondrial theory of aging: Insight from transgenic and knockout mouse models, Exp. Gerontol., 44, 256, 10.1016/j.exger.2008.12.006

Dai, 2014, Mitochondrial oxidative stress in aging and healthspan, Longev. Healthspan, 3, 6, 10.1186/2046-2395-3-6

Hamilton, R.T., Walsh, M.E., and van Remmen, H. (2012). Mouse models of oxidative stress indicate a role for modulating healthy aging. J. Clin. Exp. Pathol.

Berry, 2013, The p66Shc gene paves the way for healthspan: Evolutionary and mechanistic perspectives, Neurosci. Biobehav. Rev., 37, 790, 10.1016/j.neubiorev.2013.03.005

Wanagat, 2010, Mitochondrial oxidative stress and mammalian healthspan, Mech. Ageing Dev., 131, 527, 10.1016/j.mad.2010.06.002

Sies, 2015, Oxidative stress: A concept in redox biology and medicine, Redox Biol., 4, 180, 10.1016/j.redox.2015.01.002

Beckman, 1996, Nitric oxide, superoxide, and peroxynitrite: The good, the bad, and ugly, Am. J. Physiol., 271, C1424, 10.1152/ajpcell.1996.271.5.C1424

Daiber, 2007, Enzyme inhibition by peroxynitrite-mediated tyrosine nitration and thiol oxidation, Curr. Enzym. Inhib., 3, 103, 10.2174/157340807780598369

Beckman, 2002, Protein tyrosine nitration and peroxynitrite, FASEB J., 16, 1144, 10.1096/fj.02-0133lte

Quijano, 1997, Pathways of peroxynitrite oxidation of thiol groups, Biochem. J., 322, 167, 10.1042/bj3220167

Crow, 1996, Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts, Proc. Natl. Acad. Sci. USA, 93, 11853, 10.1073/pnas.93.21.11853

Kuzkaya, 2003, Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: Implications for uncoupling endothelial nitric-oxide synthase, J. Biol. Chem., 278, 22546, 10.1074/jbc.M302227200

Schulz, 2008, Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension, Antioxid. Redox Signal., 10, 1115, 10.1089/ars.2007.1989

Yoshida, 2000, Alterations of tetrahydrobiopterin biosynthesis and pteridine levels in mouse tissues during growth and aging, Brain Dev., 22, S45, 10.1016/S0387-7604(00)00144-3

Blackwell, 2004, Mechanisms of aging-induced impairment of endothelium-dependent relaxation: Role of tetrahydrobiopterin, Am. J. Physiol. Heart Circ. Physiol., 287, H2448, 10.1152/ajpheart.00248.2004

Chen, 2010, S-glutathionylation uncouples eNOS and regulates its cellular and vascular function, Nature, 468, 1115, 10.1038/nature09599

Schulz, 2014, Mitochondrial redox signaling: Interaction of mitochondrial reactive oxygen species with other sources of oxidative stress, Antioxid. Redox Signal., 20, 308, 10.1089/ars.2012.4609

Zou, 2002, Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite, J. Clin. Investig., 109, 817, 10.1172/JCI0214442

Forstermann, 2006, Endothelial nitric oxide synthase in vascular disease: From marvel to menace, Circulation, 113, 1708, 10.1161/CIRCULATIONAHA.105.602532

Soucy, 2006, Impaired shear stress-induced nitric oxide production through decreased NOS phosphorylation contributes to age-related vascular stiffness, J. Appl. Physiol., 101, 1751, 10.1152/japplphysiol.00138.2006

Cave, 2006, Nadph oxidases in cardiovascular health and disease, Antioxid. Redox signal., 8, 691, 10.1089/ars.2006.8.691

Griendling, 2000, NAD(P)H oxidase: Role in cardiovascular biology and disease, Circ. Res., 86, 494, 10.1161/01.RES.86.5.494

Paneni, 2013, Deletion of the activated protein-1 transcription factor JunD induces oxidative stress and accelerates age-related endothelial dysfunction, Circulation, 127, 1229, 10.1161/CIRCULATIONAHA.112.000826

Roubenoff, 1998, Monocyte cytokine production in an elderly population: Effect of age and inflammation, J. Gerontol. Ser. A, 53, M20, 10.1093/gerona/53A.1.M20

Moe, 2006, 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., 10, 231, 10.1111/j.1582-4934.2006.tb00304.x

Karbach, 2014, eNOS uncoupling in cardiovascular diseases—The role of oxidative stress and inflammation, Curr. Pharm. Des., 20, 3579, 10.2174/13816128113196660748

Nandi, 2010, TNF-α modulates INOS expression in an experimental rat model of indomethacin-induced jejunoileitis, Mol. Cell. Biochem., 336, 17, 10.1007/s11010-009-0259-2

Ungvari, 2003, 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., 23, 418, 10.1161/01.ATV.0000061735.85377.40

Busik, 2008, Hyperglycemia-induced reactive oxygen species toxicity to endothelial cells is dependent on paracrine mediators, Diabetes, 57, 1952, 10.2337/db07-1520

Csiszar, 2007, Vasculoprotective effects of anti-tumor necrosis factor-α treatment in aging, Am. J. Pathol., 170, 388, 10.2353/ajpath.2007.060708

Ferrucci, 2005, The origins of age-related proinflammatory state, Blood, 105, 2294, 10.1182/blood-2004-07-2599

Wenzel, 2011, Lysozyme M-positive monocytes mediate angiotensin II-induced arterial hypertension and vascular dysfunction, Circulation, 124, 1370, 10.1161/CIRCULATIONAHA.111.034470

Guzik, 2007, Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction, J. Exp. Med., 204, 2449, 10.1084/jem.20070657

Harman, 1972, The biologic clock: The mitochondria?, J. Am. Geriatr. Soc., 20, 145, 10.1111/j.1532-5415.1972.tb00787.x

Lewis, 2007, Lack of the antioxidant enzyme glutathione peroxidase-1 accelerates atherosclerosis in diabetic apolipoprotein e-deficient mice, Circulation, 115, 2178, 10.1161/CIRCULATIONAHA.106.664250

Forgione, 2002, Heterozygous cellular glutathione peroxidase deficiency in the mouse: Abnormalities in vascular and cardiac function and structure, Circulation, 106, 1154, 10.1161/01.CIR.0000026820.87824.6A

Chrissobolis, 2008, Glutathione peroxidase-1 plays a major role in protecting against angiotensin II-induced vascular dysfunction, Hypertension, 51, 872, 10.1161/HYPERTENSIONAHA.107.103572

Blankenberg, 2003, Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease, N. Engl. J. Med., 349, 1605, 10.1056/NEJMoa030535

Steven, 2014, 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., 20, 247, 10.1089/ars.2012.4953

Hausding, 2013, CD40L contributes to angiotensin II-induced pro-thrombotic state, vascular inflammation, oxidative stress and endothelial dysfunction, Basic Res. Cardiol., 108, 386, 10.1007/s00395-013-0386-5

Fleming, 2001, Phosphorylation of Thr495 regulates Ca2+/calmodulin-dependent endothelial nitric oxide synthase activity, Circ. Res., 88, E68, 10.1161/hh1101.092677

Lin, 2003, Phosphorylation of threonine 497 in endothelial nitric-oxide synthase coordinates the coupling of l-arginine metabolism to efficient nitric oxide production, J. Biol. Chem., 278, 44719, 10.1074/jbc.M302836200

Loot, 2009, Angiotensin ii impairs endothelial function via tyrosine phosphorylation of the endothelial nitric oxide synthase, J. Exp. Med., 206, 2889, 10.1084/jem.20090449

Brune, 1990, Activation of soluble guanylate cyclase by carbon monoxide and inhibition by superoxide anion, Eur. J. Biochem., 192, 683, 10.1111/j.1432-1033.1990.tb19276.x

Weber, 2001, The effect of peroxynitrite on the catalytic activity of soluble guanylyl cyclase, Free Radic. Biol. Med., 31, 1360, 10.1016/S0891-5849(01)00706-7

Artz, 2002, Effects of nitroglycerin on soluble guanylate cyclase: Implications for nitrate tolerance, J. Biol. Chem., 277, 18253, 10.1074/jbc.C200170200

Crassous, 2012, Soluble guanylyl cyclase is a target of angiotensin II-induced nitrosative stress in a hypertensive rat model, Am. J. Physiol. Heart Circ. Physiol., 303, H597, 10.1152/ajpheart.00138.2012

Mayer, 2009, Inactivation of soluble guanylate cyclase by stoichiometric S-nitrosation, Mol. Pharmacol., 75, 886, 10.1124/mol.108.052142

Sayed, 2008, Nitroglycerin-induced S-nitrosylation and desensitization of soluble guanylyl cyclase contribute to nitrate tolerance, Circ. Res., 103, 606, 10.1161/CIRCRESAHA.108.175133

Stasch, 2006, Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels, J. Clin. Investig., 116, 2552, 10.1172/JCI28371

Chen, 2000, 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., 86, 520, 10.1161/01.RES.86.5.520

Ruetten, 1999, Downregulation of soluble guanylyl cyclase in young and aging spontaneously hypertensive rats, Circ. Res., 85, 534, 10.1161/01.RES.85.6.534

Kloss, 2000, Aging and chronic hypertension decrease expression of rat aortic soluble guanylyl cyclase, Hypertension, 35, 43, 10.1161/01.HYP.35.1.43

Lubos, 2010, Glutathione peroxidase-1 modulates lipopolysaccharide-induced adhesion molecule expression in endothelial cells by altering CD14 expression, FASEB J., 24, 2525, 10.1096/fj.09-147421

Kessler, 1997, Inhibition of inducible nitric oxide synthase restores endothelium-dependent relaxations in proinflammatory mediator-induced blood vessels, Arterioscler. Thromb. Vasc. Biol., 17, 1746, 10.1161/01.ATV.17.9.1746

Prabhu, 2002, 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., 366, 203, 10.1042/bj20020256

Bulua, 2011, Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS), J. Exp. Med., 208, 519, 10.1084/jem.20102049

West, 2011, TLR signalling augments macrophage bactericidal activity through mitochondrial ROS, Nature, 472, 476, 10.1038/nature09973

Zhou, 2011, A role for mitochondria in NLRP3 inflammasome activation, Nature, 469, 221, 10.1038/nature09663

Zhou, 2010, Thioredoxin-interacting protein links oxidative stress to inflammasome activation, Nat. Immunol., 11, 136, 10.1038/ni.1831

Smith, 2006, 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, 5, 391, 10.1111/j.1474-9726.2006.00232.x

Crabtree, 2013, Integrated redox sensor and effector functions for tetrahydrobiopterin- and glutathionylation-dependent endothelial nitric-oxide synthase uncoupling, J. Biol. Chem., 288, 561, 10.1074/jbc.M112.415992

Schriner, 2005, Extension of murine life span by overexpression of catalase targeted to mitochondria, Science, 308, 1909, 10.1126/science.1106653

Barja, 2000, Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals, FASEB J., 14, 312, 10.1096/fasebj.14.2.312

Sastre, 2003, The role of mitochondrial oxidative stress in aging, Free Radic. Biol. Med., 35, 1, 10.1016/S0891-5849(03)00184-9

Madamanchi, 2007, Mitochondrial dysfunction in atherosclerosis, Circ. Res., 100, 460, 10.1161/01.RES.0000258450.44413.96

Eide, 2001, 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., 61, 5378

Hogue, 2001, DNA repair and aging in mouse liver: 8-oxodG glycosylase activity increase in mitochondrial but not in nuclear extracts, Free Radic. Biol. Med., 30, 916, 10.1016/S0891-5849(01)00483-X

Croteau, 1999, Age-associated increase in 8-oxo-deoxyguanosine glycosylase/ap lyase activity in rat mitochondria, Nucleic Acids Res., 27, 1935, 10.1093/nar/27.8.1935

Trifunovic, 2004, Premature ageing in mice expressing defective mitochondrial DNA polymerase, Nature, 429, 417, 10.1038/nature02517

Lewis, 2007, Decreased mtDNA, oxidative stress, cardiomyopathy, and death from transgenic cardiac targeted human mutant polymerase γ, Lab. Investig., 87, 326, 10.1038/labinvest.3700523

Finsterer, 2006, Overview on visceral manifestations of mitochondrial disorders, Neth. J. Med., 64, 61

Anan, 1995, Cardiac involvement in mitochondrial diseases. A study on 17 patients with documented mitochondrial DNA defects, Circulation, 91, 955, 10.1161/01.CIR.91.4.955

Pinsky, 1994, Cardiac preservation is enhanced in a heterotopic rat transplant model by supplementing the nitric oxide pathway, J. Clin. Investig., 93, 2291, 10.1172/JCI117230

Zeviani, 2004, Mitochondrial disorders, Brain, 127, 2153, 10.1093/brain/awh259

Ballinger, 2002, Mitochondrial integrity and function in atherogenesis, Circulation, 106, 544, 10.1161/01.CIR.0000023921.93743.89

Sevini, 2014, mtDNA mutations in human aging and longevity: Controversies and new perspectives opened by high-throughput technologies, Exp.Gerontol., 56, 234, 10.1016/j.exger.2014.03.022

Itsara, 2014, Oxidative stress is not a major contributor to somatic mitochondrial DNA mutations, PLoS Genet., 10, e1003974, 10.1371/journal.pgen.1003974

Larsson, 2010, Somatic mitochondrial DNA mutations in mammalian aging, Annu. Rev. Biochem., 79, 683, 10.1146/annurev-biochem-060408-093701

2004, Endogenous DNA damage in humans: A review of quantitative data, Mutagenesis, 19, 169, 10.1093/mutage/geh025

Kennedy, 2013, Ultra-sensitive sequencing reveals an age-related increase in somatic mitochondrial mutations that are inconsistent with oxidative damage, PLoS Genet., 9, e1003794, 10.1371/journal.pgen.1003794

Cha, 2015, The role of mitochondrial DNA mutation on neurodegenerative diseases, Exp. Mol. Med., 47, e150, 10.1038/emm.2014.122

Reddy, 2009, Amyloid β, mitochondrial structural and functional dynamics in alzheimer’s disease, Exp. Neurol., 218, 286, 10.1016/j.expneurol.2009.03.042

Canugovi, 2014, Base excision DNA repair levels in mitochondrial lysates of alzheimer’s disease, Neurobiol. Aging, 35, 1293, 10.1016/j.neurobiolaging.2014.01.004

Krishnan, 2012, Mitochondrial DNA deletions cause the biochemical defect observed in alzheimer’s disease, Neurobiol. Aging, 33, 2210, 10.1016/j.neurobiolaging.2011.08.009

Muftuoglu, 2014, Formation and repair of oxidative damage in the mitochondrial DNA, Mitochondrion, 17, 164, 10.1016/j.mito.2014.03.007

Liu, 2010, DNA repair in mammalian mitochondria: Much more than we thought?, Environ. Mol. Mutagen., 51, 417, 10.1002/em.20576

Bogenhagen, 1999, Repair of mtDNA in vertebrates, Am. J. Hum. Genet., 64, 1276, 10.1086/302392

Nishioka, 1999, Expression and differential intracellular localization of two major forms of human 8-oxoguanine DNA glycosylase encoded by alternatively spliced OGG1 mRNAs, Mol. Biol. Cell, 10, 1637, 10.1091/mbc.10.5.1637

Nilsen, 1997, Nuclear and mitochondrial uracil-DNA glycosylases are generated by alternative splicing and transcription from different positions in the UNG gene, Nucleic Acids Res., 25, 750, 10.1093/nar/25.4.750

Ikeda, 2002, Differential intracellular localization of the human and mouse endonuclease III homologs and analysis of the sorting signals, DNA Repair, 1, 847, 10.1016/S1568-7864(02)00145-3

Hu, 2005, Repair of formamidopyrimidines in DNA involves different glycosylases: Role of the OGG1, NTH1, and NEIL1 enzymes, J. Biol. Chem., 280, 40544, 10.1074/jbc.M508772200

Ohtsubo, 2000, 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., 28, 1355, 10.1093/nar/28.6.1355

Park, 2014, Human AP endonuclease 1: A potential marker for the prediction of environmental carcinogenesis risk, Oxidative Med. Cell. Longev., 2014, 730301, 10.1155/2014/730301

Mason, 2003, Mismatch repair activity in mammalian mitochondria, Nucleic Acids Res., 31, 1052, 10.1093/nar/gkg167

Mason, 2009, Novel DNA mismatch-repair activity involving YB-1 in human mitochondria, DNA Repair, 8, 704, 10.1016/j.dnarep.2009.01.021

Pohjoismaki, 2009, Human heart mitochondrial DNA is organized in complex catenated networks containing abundant four-way junctions and replication forks, J. Biol. Chem., 284, 21446, 10.1074/jbc.M109.016600

Chen, 2013, Mechanism of homologous recombination and implications for aging-related deletions in mitochondrial DNA, Microbiol. Mol. Biol. Rev., 77, 476, 10.1128/MMBR.00007-13

Chen, 1993, MGM101, a nuclear gene involved in maintenance of the mitochondrial genome in saccharomyces cerevisiae, Nucleic Acids Res., 21, 3473, 10.1093/nar/21.15.3473

Gredilla, 2012, Nuclear and mitochondrial DNA repair in selected eukaryotic aging model systems, Oxidative Med. Cell. Longev., 2012, 282438, 10.1155/2012/282438

Bender, 2006, High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease, Nat. Genet., 38, 515, 10.1038/ng1769

Chen, 2002, Age-dependent decline of DNA repair activity for oxidative lesions in rat brain mitochondria, J. Neurochem., 81, 1273, 10.1046/j.1471-4159.2002.00916.x

Daiber, 2009, Nitrate tolerance as a model of vascular dysfunction: Roles for mitochondrial aldehyde dehydrogenase and mitochondrial oxidative stress, Pharmacol. Rep., 61, 33, 10.1016/S1734-1140(09)70005-2

Daiber, 2004, Oxidative stress and mitochondrial aldehyde dehydrogenase activity: A comparison of pentaerythritol tetranitrate with other organic nitrates, Mol. Pharmacol., 66, 1372, 10.1124/mol.104.002600

Sydow, 2004, Central role of mitochondrial aldehyde dehydrogenase and reactive oxygen species in nitroglycerin tolerance and cross-tolerance, J. Clin. Investig., 113, 482, 10.1172/JCI200419267

Esplugues, 2006, Complex I dysfunction and tolerance to nitroglycerin: An approach based on mitochondrial-targeted antioxidants, Circ. Res., 99, 1067, 10.1161/01.RES.0000250430.62775.99

Wenzel, 2008, First evidence for a crosstalk between mitochondrial and nadph oxidase-derived reactive oxygen species in nitroglycerin-triggered vascular dysfunction, Antioxid. Redox Signal., 10, 1435, 10.1089/ars.2007.1969

Dikalov, 2014, Nox2-induced production of mitochondrial superoxide in angiotensin II-mediated endothelial oxidative stress and hypertension, Antioxid. Redox Signal., 20, 281, 10.1089/ars.2012.4918

Doughan, 2008, Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: Linking mitochondrial oxidative damage and vascular endothelial dysfunction, Circ. Res., 102, 488, 10.1161/CIRCRESAHA.107.162800

Nazarewicz, 2013, Nox2 as a potential target of mitochondrial superoxide and its role in endothelial oxidative stress, Am. J. Physiol. Heart Circ. Physiol., 305, H1131, 10.1152/ajpheart.00063.2013

Brandes, 2005, Triggering mitochondrial radical release: A new function for NADPH oxidases, Hypertension, 45, 847, 10.1161/01.HYP.0000165019.32059.b2

Kimura, 2005, Mitochondria-derived reactive oxygen species and vascular MAP kinases: Comparison of angiotensin II and diazoxide, Hypertension, 45, 438, 10.1161/01.HYP.0000157169.27818.ae

Dikalova, 2010, Therapeutic targeting of mitochondrial superoxide in hypertension, Circ. Res., 107, 106, 10.1161/CIRCRESAHA.109.214601

Fukui, 1997, p22phox mRNA expression and NADPH oxidase activity are increased in aortas from hypertensive rats, Circ. Res., 80, 45, 10.1161/01.RES.80.1.45

Cheresh, 2013, Oxidative stress and pulmonary fibrosis, Biochim. Biophys. Acta, 1832, 1028, 10.1016/j.bbadis.2012.11.021

Nazarewicz, 2013, Mitochondrial ROS in the prohypertensive immune response, Am. J. Physiol. Regul. Integr. Comp. Physiol., 305, R98, 10.1152/ajpregu.00208.2013

Bender, 2008, Adaptive antioxidant methionine accumulation in respiratory chain complexes explains the use of a deviant genetic code in mitochondria, Proc. Natl. Acad. Sci. USA, 105, 16496, 10.1073/pnas.0802779105

Moskovitz, 2001, Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals, Proc. Natl. Acad. Sci. USA, 98, 12920, 10.1073/pnas.231472998

Stadtman, 2002, Cyclic oxidation and reduction of protein methionine residues is an important antioxidant mechanism, Mol. Cell. Biochem., 234–235, 3, 10.1023/A:1015916831583

Taungjaruwinai, 2009, Differential expression of the antioxidant repair enzyme methionine sulfoxide reductase (MSRA and MSRB) in human skin, Am. J. Dermatopathol., 31, 427, 10.1097/DAD.0b013e3181882c21

Mochin, 2015, Hyperglycemia and redox status regulate RUNX2 DNA-binding and an angiogenic phenotype in endothelial cells, Microvasc. Res., 97, 55, 10.1016/j.mvr.2014.09.008

Gu, 2013, Methionine sulfoxide reductase A rs10903323 G/A polymorphism is associated with increased risk of coronary artery disease in a chinese population, Clin. Biochem., 46, 1668, 10.1016/j.clinbiochem.2013.07.011

Haenold, 2008, Protection of vascular smooth muscle cells by over-expressed methionine sulphoxide reductase A: Role of intracellular localization and substrate availability, Free Radic. Res., 42, 978, 10.1080/10715760802566541

Moosmann, 2008, Mitochondrially encoded cysteine predicts animal lifespan, Aging Cell, 7, 32, 10.1111/j.1474-9726.2007.00349.x

Camici, 2008, The role of p66Shc deletion in age-associated arterial dysfunction and disease states, J. Appl. Physiol., 105, 1628, 10.1152/japplphysiol.90579.2008

Francia, 2004, Deletion of p66Shc gene protects against age-related endothelial dysfunction, Circulation, 110, 2889, 10.1161/01.CIR.0000147731.24444.4D

Gertz, 2008, Activation of the lifespan regulator p66Shc through reversible disulfide bond formation, Proc. Natl. Acad. Sci. USA, 105, 5705, 10.1073/pnas.0800691105

Pinton, 2007, Protein kinase C β and prolyl isomerase 1 regulate mitochondrial effects of the life-span determinant p66Shc, Science, 315, 659, 10.1126/science.1135380

Pinton, 2008, P66Shc, oxidative stress and aging: Importing a lifespan determinant into mitochondria, Cell. Cycle, 7, 304, 10.4161/cc.7.3.5360

Rota, 2006, Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66Shc gene, Circ. Res., 99, 42, 10.1161/01.RES.0000231289.63468.08

Yamamori, 2005, p66Shc regulates endothelial no production and endothelium-dependent vasorelaxation: Implications for age-associated vascular dysfunction, J. Mol. Cell. Cardiol., 39, 992, 10.1016/j.yjmcc.2005.09.003

Trinei, 2002, A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis, Oncogene, 21, 3872, 10.1038/sj.onc.1205513

Kaludercic, 2009, Mitochondrial pathways for ROS formation and myocardial injury: The relevance of p66Shc and monoamine oxidase, Basic Res. Cardiol., 104, 131, 10.1007/s00395-009-0008-4

Spescha, 2015, Post-ischaemic silencing of p66Shc reduces ischaemia/reperfusion brain injury and its expression correlates to clinical outcome in stroke, Eur. Heart J., 36, 1590, 10.1093/eurheartj/ehv140

Moskalev, 2014, Genetics and epigenetics of aging and longevity, Cell. Cycle, 13, 1063, 10.4161/cc.28433

Barbot, 2002, 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., 30, 2365, 10.1093/nar/30.11.2365

Narita, 2003, Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence, Cell., 113, 703, 10.1016/S0092-8674(03)00401-X

Tsurumi, 2012, Global heterochromatin loss: A unifying theory of aging?, Epigenetics, 7, 680, 10.4161/epi.20540

McCauley, 2014, Histone methylation and aging: Lessons learned from model systems, Biochim. Biophys. Acta, 1839, 1454, 10.1016/j.bbagrm.2014.05.008

Bilsland, 2013, Microrna and senescence: The senectome, integration and distributed control, Crit. Rev. Oncog., 18, 373, 10.1615/CritRevOncog.2013007197

Boon, 2013, MicroRNA-34a regulates cardiac ageing and function, Nature, 495, 107, 10.1038/nature11919

Guarner, 2015, Low-grade systemic inflammation connects aging, metabolic syndrome and cardiovascular disease, Interdiscip. Top. Gerontol., 40, 99

Howcroft, 2013, The role of inflammation in age-related disease, Aging, 5, 84, 10.18632/aging.100531

Mercken, 2013, Metformin improves healthspan and lifespan in mice, Nat. Commun., 4, 2192, 10.1038/ncomms3192

Wilson, 1994, Established risk factors and coronary artery disease: The framingham study, Am. J. Hypertens., 7, 7S, 10.1093/ajh/7.7.7S

Munzel, 2008, Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction, Ann. Med., 40, 180, 10.1080/07853890701854702

Munzel, 2010, Is oxidative stress a therapeutic target in cardiovascular disease?, Eur. Heart J., 31, 2741, 10.1093/eurheartj/ehq396

Schachinger, 2000, Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease, Circulation, 101, 1899, 10.1161/01.CIR.101.16.1899

Gori, 2011, Oxidative stress and endothelial dysfunction: Therapeutic implications, Ann. Med., 43, 259, 10.3109/07853890.2010.543920

Chen, 2012, Free radical biology of the cardiovascular system, Clin. Sci., 123, 73, 10.1042/CS20110562

Kimura, 1999, Impaired endothelial function in hypertensive elderly patients evaluated by high resolution ultrasonography, Can. J. Cardiol., 15, 563

Wray, 2012, Acute reversal of endothelial dysfunction in the elderly after antioxidant consumption, Hypertension, 59, 818, 10.1161/HYPERTENSIONAHA.111.189456

Jousilahti, 1999, 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, 99, 1165, 10.1161/01.CIR.99.9.1165

Holzer, 2013, Aging affects high-density lipoprotein composition and function, Biochim. Biophys. Acta, 1831, 1442, 10.1016/j.bbalip.2013.06.004

Besler, 2010, High-density lipoprotein-mediated anti-atherosclerotic and endothelial-protective effects: A potential novel therapeutic target in cardiovascular disease, Curr. Pharm. Des., 16, 1480, 10.2174/138161210791051013

Wu, 2015, Maternal treatment of spontaneously hypertensive rats with pentaerythritol tetranitrate reduces blood pressure in female offspring, Hypertension, 65, 232, 10.1161/HYPERTENSIONAHA.114.04416

LaRocca, 2014, Mitochondria-targeted antioxidant (MitoQ) ameliorates age-related arterial endothelial dysfunction in mice, J. Physiol., 592, 2549, 10.1113/jphysiol.2013.268680

Geleijnse, 1999, Dietary antioxidants and risk of myocardial infarction in the elderly: The rotterdam study, Am. J. Clin. Nutr., 69, 261, 10.1093/ajcn/69.2.261