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Cited by 950Mitochondrial Function and PathologyCardiac Ischemia and ReperfusionRedox biology and oxidative stress

Mitochondrial dysfunction and oxidative stress in heart disease

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Peoples, Jessica N., Saraf, Anita, Ghazal, Nasab, Pham, Tyler T., Kwong, Jennifer Q.·2019·Experimental & Molecular Medicine
DOI 10.1038/s12276-019-0355-7PMC PMC6923355
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Abstract

Beyond their role as a cellular powerhouse, mitochondria are emerging as integral players in molecular signaling and cell fate determination through reactive oxygen species (ROS). While ROS production has historically been portrayed as an unregulated process driving oxidative stress and disease pathology, contemporary studies reveal that ROS also facilitate normal physiology. Mitochondria are especially abundant in cardiac tissue; hence, mitochondrial dysregulation and ROS production are thought to contribute significantly to cardiac pathology. Moreover, there is growing appreciation that medical therapies designed to mediate mitochondrial ROS production can be important strategies to ameliorate cardiac disease. In this review, we highlight evidence from animal models that illustrates the strong connections between mitochondrial ROS and cardiac disease, discuss advancements in the development of mitochondria-targeted antioxidant therapies, and identify challenges faced in bringing such therapies into the clinic.

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  • Under unregulated conditions, elevated ROS and NADPH oxidase (NOX) levels have been implicated in cardiac hypertrophy, heart failure, cardiac ischemia-reperfusion injury, and diabetic cardiomyopathy.

    “Under unregulated conditions, elevated ROS and NADPH oxidase (NOX) levels have been implicated in cardiac hypertrophy, heart failure, cardiac ischemia–reperfusion injury, and diabetic cardiomyopathy91.”

    From Key points for the development of antioxidant cocktails to prevent cellular stress and damage caused by reactive oxygen species (ROS) during manned space missions (2021) · cites this paper as [91]

    The Introduction (page unavailable) implicates unregulated ROS production and oxidative stress in all four listed conditions. The Heart failure section (page unavailable) also reports increased NOX expression in heart failure and links NOX2 and NOX4 to hypertrophy. The passages on ischemia–reperfusion injury and diabetic cardiomyopathy discuss ROS, but do not establish elevated NOX levels in those conditions. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Under normal physiological conditions, ROS regulates heart development, cardiomyocyte differentiation, vascular tone, and excitation contraction coupling.

    “Under normal physiological conditions, ROS regulates heart development, cardiomyocyte differentiation, vascular tone, and excitation contraction coupling91.”

    From Key points for the development of antioxidant cocktails to prevent cellular stress and damage caused by reactive oxygen species (ROS) during manned space missions (2021) · cites this paper as [91]

    The Introduction states that, under physiological conditions, cardiac ROS signaling regulates heart development, vascular tone, and excitation–contraction coupling. It names cardiomyocyte maturation, however, rather than cardiomyocyte differentiation; our copy does not establish that specific part of the claim. (LLM, conf=0.88)

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  1. [1]Burgoyne JR Mongue-Din H Eaton P Shah AM Redox signaling in cardiac physiology and pathology Circ. Res. 2012 111 1091 1106 10.1161/CIRCRESAHA.111.255216 23023511 · DOI
  2. [2]Richardson AG Schadt EE The role of macromolecular damage in aging and age-related disease J. Gerontol. A 2014 69 Suppl. 1 S28 S32 10.1093/gerona/glu056 24833583 · DOI
  3. [3]Maulik SK Kumar S Oxidative stress and cardiac hypertrophy: a review Toxicol. Mech. Methods 2012 22 359 366 10.3109/15376516.2012.666650 22394344 · DOI
  4. [4]Tsutsui H Kinugawa S Matsushima S Oxidative stress and heart failure Am. J. Physiol. Heart Circ. Physiol. 2011 301 H2181 H2190 10.1152/ajpheart.00554.2011 21949114 · DOI
  5. [5]Misra MK Sarwat M Bhakuni P Tuteja R Tuteja N Oxidative stress and ischemic myocardial syndromes Med. Sci. Monit. 2009 15 RA209 RA219 19789524
  6. [6]Liu Q Wang S Cai L Diabetic cardiomyopathy and its mechanisms: role of oxidative stress and damage J. Diabetes Investig. 2014 5 623 634 10.1111/jdi.12250 25422760 PMC4234223 · DOI
  7. [8]Ardanaz N Lack of glutathione peroxidase 1 accelerates cardiac-specific hypertrophy and dysfunction in angiotensin II hypertension Hypertension 2010 55 116 123 10.1161/HYPERTENSIONAHA.109.135715 19917877 PMC3061336 · DOI
  8. [9]Chen Z Prevention of ischemia/reperfusion-induced cardiac apoptosis and injury by melatonin is independent of glutathione peroxdiase 1 J. Pineal Res. 2009 46 235 241 10.1111/j.1600-079X.2008.00654.x 19141089 PMC2752734 · DOI
  9. [10]Hu C Loss of thioredoxin 2 alters mitochondrial respiratory function and induces cardiomyocyte hypertrophy Exp. Cell Res. 2018 372 61 72 10.1016/j.yexcr.2018.09.010 30236513 · DOI
  10. [11]Huang Q Thioredoxin-2 inhibits mitochondrial reactive oxygen species generation and apoptosis stress kinase-1 activity to maintain cardiac function Circulation 2015 131 1082 1097 10.1161/CIRCULATIONAHA.114.012725 25628390 PMC4374031 · DOI
  11. [13]Daubert MA Novel mitochondria-targeting peptide in heart failure treatment: a randomized, placebo-controlled trial of Elamipretide Circ. Heart Fail 2017 10 e004389 10.1161/CIRCHEARTFAILURE.117.004389 29217757 · DOI
  12. [14]Pryde KR Hirst J Superoxide is produced by the reduced flavin in mitochondrial complex I: a single, unified mechanism that applies during both forward and reverse electron transfer J. Biol. Chem. 2011 286 18056 18065 10.1074/jbc.M110.186841 21393237 PMC3093879 · DOI
  13. [15]Kushnareva Y Murphy AN Andreyev A Complex I-mediated reactive oxygen species generation: modulation by cytochrome c and NAD(P)+ oxidation-reduction state Biochem J. 2002 368 545 553 10.1042/bj20021121 12180906 PMC1222999 · DOI
  14. [17]Turrens JF Alexandre A Lehninger AL Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria Arch. Biochem. Biophys. 1985 237 408 414 10.1016/0003-9861(85)90293-0 2983613 · DOI · Paper page
  15. [18]Orsini F The life span determinant p66Shc localizes to mitochondria where it associates with mitochondrial heat shock protein 70 and regulates trans-membrane potential J. Biol. Chem. 2004 279 25689 25695 10.1074/jbc.M401844200 15078873 · DOI
  16. [19]Giorgio M Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis Cell 2005 122 221 233 10.1016/j.cell.2005.05.011 16051147 · DOI · Paper page
  17. [20]Kuroda J NADPH oxidase 4 (NOX4) is a major source of oxidative stress in the failing heart Proc. Natl Acad. Sci. USA 2010 107 15565 15570 10.1073/pnas.1002178107 20713697 PMC2932625 · DOI · Paper page
  18. [21]Block K Gorin Y Abboud HE Subcellular localization of NOX4 and regulation in diabetes Proc. Natl Acad. Sci. USA 2009 106 14385 14390 10.1073/pnas.0906805106 19706525 PMC2732863 · DOI
  19. [22]Shanmugasundaram K NOX4 functions as a mitochondrial energetic sensor coupling cancer metabolic reprogramming to drug resistance Nat. Commun. 2017 8 997 10.1038/s41467-017-01106-1 29051480 PMC5648812 · DOI
  20. [23]Takac I The E-loop is involved in hydrogen peroxide formation by the NADPH oxidase NOX4 J. Biol. Chem. 2011 286 13304 13313 10.1074/jbc.M110.192138 21343298 PMC3075677 · DOI
  21. [24]Suzuki Y Ali M Fischer M Riemer J Human copper chaperone for superoxide dismutase 1 mediates its own oxidation-dependent import into mitochondria Nat. Commun. 2013 4 2430 10.1038/ncomms3430 24026195 · DOI
  22. [25]Kawamata H Manfredi G Import, maturation, and function of SOD1 and its copper chaperone CCS in the mitochondrial intermembrane space Antioxid. Redox Signal. 2010 13 1375 1384 10.1089/ars.2010.3212 20367259 PMC2962758 · DOI
  23. [26]Chen Y Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS EMBO Rep. 2011 12 534 541 10.1038/embor.2011.65 21566644 PMC3128277 · DOI · Paper page
  24. [27]Radi R Detection of catalase in rat heart mitochondria J. Biol. Chem. 1991 266 22028 22034 1657986
  25. [28]Andreyev AY Kushnareva YE Murphy AN Starkov AA Mitochondrial ROS metabolism: 10 years later Biochemistry (Mosc.) 2015 80 517 531 10.1134/S0006297915050028 26071769 PMC4511471 · DOI
  26. [29]Mari M Morales A Colell A Garcia-Ruiz C Fernandez-Checa JC Mitochondrial glutathione, a key survival antioxidant Antioxid. Redox Signal. 2009 11 2685 2700 10.1089/ars.2009.2695 19558212 PMC2821140 · DOI
  27. [30]Perkins A Nelson KJ Parsonage D Poole LB Karplus PA Peroxiredoxins: guardians against oxidative stress and modulators of peroxide signaling Trends Biochem. Sci. 2015 40 435 445 10.1016/j.tibs.2015.05.001 26067716 PMC4509974 · DOI
  28. [31]Murphy E Steenbergen C Mechanisms underlying acute protection from cardiac ischemia–reperfusion injury Physiol. Rev. 2008 88 581 609 10.1152/physrev.00024.2007 18391174 PMC3199571 · DOI
  29. [32]Haworth RA Hunter DR The Ca2+-induced membrane transition in mitochondria. II. Nature of the Ca2+ trigger site Arch. Biochem. Biophys. 1979 195 460 467 10.1016/0003-9861(79)90372-2 38751 · DOI · Paper page
  30. [33]Hunter DR Haworth RA The Ca2+-induced membrane transition in mitochondria. I. The protective mechanisms Arch. Biochem. Biophys. 1979 195 453 459 10.1016/0003-9861(79)90371-0 383019 · DOI
  31. [34]Hunter DR Haworth RA The Ca2+-induced membrane transition in mitochondria. III. Transitional Ca2+ release Arch. Biochem. Biophys. 1979 195 468 477 10.1016/0003-9861(79)90373-4 112926 · DOI · Paper page
  32. [35]Kwong JQ Molkentin JD Physiological and pathological roles of the mitochondrial permeability transition pore in the heart Cell Metab. 2015 21 206 214 10.1016/j.cmet.2014.12.001 25651175 PMC4616258 · DOI
  33. [36]Hausenloy DJ Duchen MR Yellon DM Inhibiting mitochondrial permeability transition pore opening at reperfusion protects against ischaemia–reperfusion injury Cardiovasc. Res. 2003 60 617 625 10.1016/j.cardiores.2003.09.025 14659807 · DOI
  34. [37]Hausenloy DJ Maddock HL Baxter GF Yellon DM Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning? Cardiovasc. Res. 2002 55 534 543 10.1016/S0008-6363(02)00455-8 12160950 · DOI
  35. [38]Hausenloy DJ Yellon DM The mitochondrial permeability transition pore: its fundamental role in mediating cell death during ischaemia and reperfusion J. Mol. Cell. Cardiol. 2003 35 339 341 10.1016/S0022-2828(03)00043-9 12689812 · DOI
  36. [40]Trankle C Thurber CJ Toldo S Abbate A Mitochondrial membrane permeability inhibitors in acute myocardial infarction: still awaiting translation JACC Basic Transl. Sci. 2016 1 524 535 10.1016/j.jacbts.2016.06.012 30167535 PMC6113419 · DOI
  37. [41]Zhang M Contractile function during angiotensin-II activation: increased NOX2 activity modulates cardiac calcium handling via phospholamban phosphorylation J. Am. Coll. Cardiol. 2015 66 261 272 10.1016/j.jacc.2015.05.020 26184620 PMC4509515 · DOI
  38. [42]Zhang M NADPH oxidase-4 mediates protection against chronic load-induced stress in mouse hearts by enhancing angiogenesis Proc. Natl Acad. Sci. USA 2010 107 18121 18126 10.1073/pnas.1009700107 20921387 PMC2964252 · DOI
  39. [43]Zhang M Perino A Ghigo A Hirsch E Shah AM NADPH oxidases in heart failure: poachers or gamekeepers? Antioxid. Redox Signal. 2013 18 1024 1041 10.1089/ars.2012.4550 22747566 PMC3567780 · DOI
  40. [44]Maack C Oxygen free radical release in human failing myocardium is associated with increased activity of rac1-GTPase and represents a target for statin treatment Circulation 2003 108 1567 1574 10.1161/01.CIR.0000091084.46500.BB 12963641 · DOI
  41. [45]Heymes C Increased myocardial NADPH oxidase activity in human heart failure J. Am. Coll. Cardiol. 2003 41 2164 2171 10.1016/S0735-1097(03)00471-6 12821241 · DOI
  42. [48]Duncan JG Mitochondrial dysfunction in diabetic cardiomyopathy Biochim. Biophys. Acta 2011 1813 1351 1359 10.1016/j.bbamcr.2011.01.014 21256163 PMC3149859 · DOI
  43. [49]Alsaied T Factors associated with long-term mortality after Fontan procedures: a systematic review Heart 2017 103 104 110 10.1136/heartjnl-2016-310108 28057809 · DOI
  44. [50]Teshima Y Production of reactive oxygen species in the diabetic heart. Roles of mitochondria and NADPH oxidase Circ. J. 2014 78 300 306 10.1253/circj.CJ-13-1187 24334638 · DOI
  45. [51]Schilling JD The mitochondria in diabetic heart failure: from pathogenesis to therapeutic promise Antioxid. Redox Signal. 2015 22 1515 1526 10.1089/ars.2015.6294 25761843 PMC4449623 · DOI
  46. [52]Szabadkai G Duchen MR Mitochondria: the hub of cellular Ca2+ signaling Physiology (Bethesda) 2008 23 84 94 18400691
  47. [53]Dabkowski ER Mitochondrial dysfunction in the type 2 diabetic heart is associated with alterations in spatially distinct mitochondrial proteomes Am. J. Physiol. Heart Circ. Physiol. 2010 299 H529 H540 10.1152/ajpheart.00267.2010 20543078 PMC2930393 · DOI
  48. [54]Flarsheim CE Grupp IL Matlib MA Mitochondrial dysfunction accompanies diastolic dysfunction in diabetic rat heart Am. J. Physiol. 1996 271 H192 H202 8760175
  49. [56]Dai DF Age-dependent cardiomyopathy in mitochondrial mutator mice is attenuated by overexpression of catalase targeted to mitochondria Aging Cell 2010 9 536 544 10.1111/j.1474-9726.2010.00581.x 20456298 PMC3265170 · DOI · Paper page
  50. [57]Trifunovic A Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production Proc. Natl Acad. Sci. USA 2005 102 17993 17998 10.1073/pnas.0508886102 16332961 PMC1312403 · DOI · Paper page
  51. [58]Shabalina IG Improved health-span and lifespan in mtDNA mutator mice treated with the mitochondrially targeted antioxidant SkQ1 Aging (Albany NY) 2017 9 315 339 10.18632/aging.101174 28209927 PMC5361666 · DOI
  52. [59]Trinei 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
  53. [62]Carpi A The cardioprotective effects elicited by p66(Shc) ablation demonstrate the crucial role of mitochondrial ROS formation in ischemia/reperfusion injury Biochim. Biophys. Acta 2009 1787 774 780 10.1016/j.bbabio.2009.04.001 19362067 · DOI
  54. [63]Akhmedov A Genetic deletion of the adaptor protein p66Shc increases susceptibility to short-term ischaemic myocardial injury via intracellular salvage pathways Eur. Heart J. 2015 36 516 526a 10.1093/eurheartj/ehu400 25336219 · DOI
  55. [64]Boengler K Lack of contribution of p66shc and its mitochondrial translocation to ischemia–reperfusion injury and cardioprotection by ischemic preconditioning Front. Physiol. 2017 8 733 10.3389/fphys.2017.00733 29051737 PMC5633811 · DOI
  56. [65]Kaludercic N Monoamine oxidase A-mediated enhanced catabolism of norepinephrine contributes to adverse remodeling and pump failure in hearts with pressure overload Circ. Res 2010 106 193 202 10.1161/CIRCRESAHA.109.198366 19910579 PMC2804073 · DOI
  57. [66]Kaludercic N Monoamine oxidase B prompts mitochondrial and cardiac dysfunction in pressure overloaded hearts Antioxid. Redox Signal. 2014 20 267 280 10.1089/ars.2012.4616 23581564 PMC3887464 · DOI
  58. [67]Bianchi P Oxidative stress by monoamine oxidase mediates receptor-independent cardiomyocyte apoptosis by serotonin and postischemic myocardial injury Circulation 2005 112 3297 3305 10.1161/CIRCULATIONAHA.104.528133 16286591 · DOI
  59. [68]Borchi E Enhanced ROS production by NADPH oxidase is correlated to changes in antioxidant enzyme activity in human heart failure Biochim. Biophys. Acta 2010 1802 331 338 10.1016/j.bbadis.2009.10.014 19892017 · DOI
  60. [69]Zhang J NOX4-dependent hydrogen peroxide overproduction in human atrial fibrillation and HL-1 atrial cells: relationship to hypertension Front. Physiol. 2012 3 140 22679437 PMC3367314
  61. [70]Sorescu D Superoxide production and expression of NOX family proteins in human atherosclerosis Circulation 2002 105 1429 1435 10.1161/01.CIR.0000012917.74432.66 11914250 · DOI · Paper page
  62. [71]Van Remmen H Knockout mice heterozygous for Sod2 show alterations in cardiac mitochondrial function and apoptosis Am. J. Physiol. Heart Circ. Physiol. 2001 281 H1422 H1432 10.1152/ajpheart.2001.281.3.H1422 11514315 · DOI
  63. [72]Shen X Zheng S Metreveli NS Epstein PN Protection of cardiac mitochondria by overexpression of MnSOD reduces diabetic cardiomyopathy Diabetes 2006 55 798 805 10.2337/diabetes.55.03.06.db05-1039 16505246 · DOI
  64. [73]Lim CC Glutathione peroxidase deficiency exacerbates ischemia-reperfusion injury in male but not female myocardium: insights into antioxidant compensatory mechanisms Am. J. Physiol. Heart Circ. Physiol. 2009 297 H2144 H2153 10.1152/ajpheart.00673.2009 19801492 PMC2793140 · DOI
  65. [74]Shiomi T Overexpression of glutathione peroxidase prevents left ventricular remodeling and failure after myocardial infarction in mice Circulation 2004 109 544 549 10.1161/01.CIR.0000109701.77059.E9 14744974 · DOI
  66. [75]Matsushima S Overexpression of mitochondrial peroxiredoxin-3 prevents left ventricular remodeling and failure after myocardial infarction in mice Circulation 2006 113 1779 1786 10.1161/CIRCULATIONAHA.105.582239 16585391 · DOI
  67. [77]Dai DF Mitochondrial proteome remodelling in pressure overload-induced heart failure: the role of mitochondrial oxidative stress Cardiovasc. Res. 2012 93 79 88 10.1093/cvr/cvr274 22012956 PMC3243039 · DOI · Paper page
  68. [78]Hornig B Arakawa N Kohler C Drexler H Vitamin C improves endothelial function of conduit arteries in patients with chronic heart failure Circulation 1998 97 363 368 10.1161/01.CIR.97.4.363 9468210 · DOI
  69. [79]Ellis GR Acute effects of vitamin C on platelet responsiveness to nitric oxide donors and endothelial function in patients with chronic heart failure J. Cardiovasc. Pharm. 2001 37 564 570 10.1097/00005344-200105000-00008 11336107 · DOI
  70. [80]Rimm EB Vitamin E consumption and the risk of coronary heart disease in men N. Engl. J. Med. 1993 328 1450 1456 10.1056/NEJM199305203282004 8479464 · DOI
  71. [81]Stampfer MJ Vitamin E consumption and the risk of coronary disease in women N. Engl. J. Med. 1993 328 1444 1449 10.1056/NEJM199305203282003 8479463 · DOI
  72. [82]Cook NR A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women’s Antioxidant Cardiovascular Study Arch. Intern. Med. 2007 167 1610 1618 10.1001/archinte.167.15.1610 17698683 PMC2034519 · DOI
  73. [84]Virtamo J Effect of vitamin E and beta carotene on the incidence of primary nonfatal myocardial infarction and fatal coronary heart disease Arch. Intern. Med. 1998 158 668 675 10.1001/archinte.158.6.668 9521232 · DOI
  74. [85]Tornwall ME Effect of alpha-tocopherol and beta-carotene supplementation on coronary heart disease during the 6-year post-trial follow-up in the ATBC study Eur. Heart J. 2004 25 1171 1178 10.1016/j.ehj.2004.05.007 15231376 · DOI
  75. [86]Nightingale AK Chronic oral ascorbic acid therapy worsens skeletal muscle metabolism in patients with chronic heart failure Eur. J. Heart Fail. 2007 9 287 291 10.1016/j.ejheart.2006.06.006 17023203 · DOI
  76. [87]Sochman J Vrbska J Musilova B Rocek M Infarct size limitation: acute N-acetylcysteine defense (ISLAND trial): preliminary analysis and report after the first 30 patients Clin. Cardiol. 1996 19 94 100 10.1002/clc.4960190205 8821417 · DOI
  77. [88]Horowitz JD Combined use of nitroglycerin and N-acetylcysteine in the management of unstable angina pectoris Circulation 1988 77 787 794 10.1161/01.CIR.77.4.787 3127076 · DOI
  78. [89]Arstall MA Yang J Stafford I Betts WH Horowitz JD N-acetylcysteine in combination with nitroglycerin and streptokinase for the treatment of evolving acute myocardial infarction. Safety and biochemical effects Circulation 1995 92 2855 2862 10.1161/01.CIR.92.10.2855 7586252 · DOI
  79. [90]Yesilbursa D Effect of N-acetylcysteine on oxidative stress and ventricular function in patients with myocardial infarction Heart Vessels 2006 21 33 37 10.1007/s00380-005-0854-4 16440146 · DOI
  80. [91]Pasupathy S Early use of N-acetylcysteine with nitrate therapy in patients undergoing primary percutaneous coronary intervention for ST-segmentelevationmyocardial infarction reduces myocardial infarct size (the NACIAM Trial [N-acetylcysteine in Acute Myocardial Infarction]) Circulation 2017 136 894 903 10.1161/CIRCULATIONAHA.117.027575 28634219 · DOI
  81. [92]Trnka J Blaikie FH Smith RA Murphy MP A mitochondria-targeted nitroxide is reduced to its hydroxylamine by ubiquinol in mitochondria Free Radic. Biol. Med. 2008 44 1406 1419 10.1016/j.freeradbiomed.2007.12.036 18206669 · DOI
  82. [93]Dey S DeMazumder D Sidor A Foster DB O'Rourke B Mitochondrial ROS drive sudden cardiac death and chronic proteome remodeling in heart failure Circ. Res. 2018 123 356 371 10.1161/CIRCRESAHA.118.312708 29898892 PMC6057154 · DOI
  83. [94]Hoshino A Oxidative post-translational modifications develop LONP1 dysfunction in pressure overload heart failure Circ. Heart Fail. 2014 7 500 509 10.1161/CIRCHEARTFAILURE.113.001062 24740269 · DOI
  84. [95]Ni R Therapeutic inhibition of mitochondrial reactive oxygen species with mito-TEMPO reduces diabetic cardiomyopathy Free Radic. Biol. Med. 2016 90 12 23 10.1016/j.freeradbiomed.2015.11.013 26577173 PMC5066872 · DOI
  85. [97]Neuzil J Mitochondria transmit apoptosis signalling in cardiomyocyte-like cells and isolated hearts exposed to experimental ischemia–reperfusion injury Redox Rep. 2007 12 148 162 10.1179/135100007X200227 17623522 · DOI
  86. [99]Ribeiro Junior RF MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload Free Radic. Biol. Med. 2018 117 18 29 10.1016/j.freeradbiomed.2018.01.012 29421236 PMC5866124 · DOI
  87. [100]Szeto HH First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics Br. J. Pharm. 2014 171 2029 2050 10.1111/bph.12461 PMC3976620 24117165 · DOI
  88. [101]Chicco AJ Sparagna GC Role of cardiolipin alterations in mitochondrial dysfunction and disease Am. J. Physiol. Cell Physiol. 2007 292 C33 C44 10.1152/ajpcell.00243.2006 16899548 · DOI
  89. [102]Birk AV The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin J. Am. Soc. Nephrol. 2013 24 1250 1261 10.1681/ASN.2012121216 23813215 PMC3736700 · DOI
  90. [103]Hanske J Conformational properties of cardiolipin-bound cytochrome c Proc. Natl Acad. Sci. USA 2012 109 125 130 10.1073/pnas.1112312108 22190488 PMC3252944 · DOI
  91. [105]Kloner RA Reduction of ischemia/reperfusion injury with bendavia, a mitochondria-targeting cytoprotective Peptide J. Am. Heart Assoc. 2012 1 e001644 10.1161/JAHA.112.001644 23130143 PMC3487333 · DOI
  92. [107]Brown DA Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia J. Cardiovasc. Pharm. Ther. 2014 19 121 132 10.1177/1074248413508003 PMC4103197 24288396 · DOI
  93. [108]Dai DF Global proteomics and pathway analysis of pressure-overload-induced heart failure and its attenuation by mitochondrial-targeted peptides Circ. Heart Fail. 2013 6 1067 1076 10.1161/CIRCHEARTFAILURE.113.000406 23935006 PMC3856238 · DOI
  94. [109]Sabbah HN Chronic therapy with Elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure Circ. Heart Fail. 2016 9 e002206 10.1161/CIRCHEARTFAILURE.115.002206 26839394 PMC4743543 · DOI

Cited by

Sorted by citations

Authors
Peoples, J. N., Saraf, A., Ghazal, N., Pham, T. T., & Kwong, J. Q.
Affiliations
Emory University (US)
Corresponding author
Kwong, Jennifer Q.
ORCID
Venue
Experimental & Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2019-12
Volume
51
Issue
12
Pages
1-13
ISSN
  • 1226-3613 (ISSN-L)
  • 2092-6413
DOI
10.1038/s12276-019-0355-7
PMC
PMC6923355
OpenAlex
W2995162523
Cited by
950
References
16
Citations by year
2026: 135 · 2025: 210 · 2024: 192 · 2023: 156 · 2022: 126 · 2021: 89 · 2020: 41
FWCI
5.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Experimental & Molecular Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
American Heart Association (16SDG26420043)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
mitochondrial dysfunction, oxidative stress, reactive oxygen species, heart disease, cardiac pathology, mitochondria-targeted antioxidants, cell fate determination, mitochondrial ROS production
MeSH terms
Animals, Heart Diseases, Humans, Mitochondria, Cardiomyopathies, Signal Transduction, Reactive Oxygen Species, Oxidative Stress, Mitochondrial Diseases

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