Advertisement

Mitochondrial Aldehyde Dehydrogenase in Myocardial Ischemic and Ischemia-Reperfusion Injury

  • Jie Ding
  • Zheng Yang
  • Heng MaEmail author
  • Hao Zhang
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1193)

Abstract

Myocardial ischemia-reperfusion (IR) injury during acute myocardial infarction or open-heart surgery would promote oxidative stress, leading to the accumulation of reactive aldehydes that cause cardiac damage. It has been well demonstrated that aldehyde dehydrogenase (ALDH)-2 is an important cardioprotective enzyme for its central role in the detoxification of reactive aldehydes. ALDH2 activation by small molecule activators is a promising approach for cardioprotection for myocardial IR injury.

References

  1. 1.
    Hanson MA, Fareed MT, Argenio SL, Agunwamba AO, Hanson TR (2013) Coronary artery disease. Prim Care 40:1–16.  https://doi.org/10.1016/j.pop.2012.12.001 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Mozaffarian D et al (2015) Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation 131:e29–e322.  https://doi.org/10.1161/CIR.0000000000000152 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Lejay A et al (2016) Ischemia reperfusion injury, ischemic conditioning and diabetes mellitus. J Mol Cell Cardiol 91:11–22.  https://doi.org/10.1016/j.yjmcc.2015.12.020 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Hill BG, Bhatnagar A (2009) Beyond reactive oxygen species: aldehydes as arbitrators of alarm and adaptation. Circ Res 105:1044–1046.  https://doi.org/10.1161/CIRCRESAHA.109.209791 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Milei J, Grana D (2007) R., Forcada, P. & Ambrosio, G. mitochondrial oxidative and structural damage in ischemia-reperfusion in human myocardium. Current knowledge and future directions. Front Biosci 12:1124–1130CrossRefGoogle Scholar
  6. 6.
    White CW et al (2016) Avoidance of profound hypothermia during initial reperfusion improves the functional recovery of hearts donated after circulatory death. Am J Transplant 16:773–782.  https://doi.org/10.1111/ajt.13574 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Sepehri A et al (2014) The impact of frailty on outcomes after cardiac surgery: a systematic review. J Thorac Cardiovasc Surg 148:3110–3117.  https://doi.org/10.1016/j.jtcvs.2014.07.087 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Roger VL et al (2012) Executive summary: heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation 125:188–197.  https://doi.org/10.1161/CIR.0b013e3182456d46 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Wong ND (2014) Epidemiological studies of CHD and the evolution of preventive cardiology. Nat Rev Cardiol 11:276–289.  https://doi.org/10.1038/nrcardio.2014.26 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Bonsu KO, Owusu IK, Buabeng KO, Reidpath DD, Kadirvelu A (2016) Review of novel therapeutic targets for improving heart failure treatment based on experimental and clinical studies. Therap Clin Risk Manag 12:887–906.  https://doi.org/10.2147/tcrm.s106065 CrossRefGoogle Scholar
  11. 11.
    Zhang Y, Ren J (2011) ALDH2 in alcoholic heart diseases: molecular mechanism and clinical implications. Pharmacol Ther 132:86–95.  https://doi.org/10.1016/j.pharmthera.2011.05.008 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Yin G et al (2016) ALDH2 polymorphism is associated with fasting blood glucose through alcohol consumption in Japanese men. Nagoya J Med Sci 78:183–193PubMedPubMedCentralGoogle Scholar
  13. 13.
    Yokoyama A et al (2013) Genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and liver cirrhosis, chronic calcific pancreatitis, diabetes mellitus, and hypertension among Japanese alcoholic men. Alcohol Clin Exp Res 37:1391–1401.  https://doi.org/10.1111/acer.12108 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Dakeishi M, Murata K, Sasaki M, Tamura A, Iwata T (2008) Association of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 genotypes with fasting plasma glucose levels in Japanese male and female workers. Alcohol Alcohol 43:143–147.  https://doi.org/10.1093/alcalc/agm173 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Takagi S et al (2002) Aldehyde dehydrogenase 2 gene is a risk factor for myocardial infarction in Japanese men. Hypertens Res 25:677–681CrossRefGoogle Scholar
  16. 16.
    Xu F et al (2011) Role of aldehyde dehydrogenase 2 Glu504lys polymorphism in acute coronary syndrome. J Cell Mol Med 15:1955–1962.  https://doi.org/10.1111/j.1582-4934.2010.01181.x CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Jo SA et al (2007) A Glu487Lys polymorphism in the gene for mitochondrial aldehyde dehydrogenase 2 is associated with myocardial infarction in elderly Korean men. Clin Chim Acta 382:43–47.  https://doi.org/10.1016/j.cca.2007.03.016 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Bian Y et al (2010) The polymorphism in aldehyde dehydrogenase-2 gene is associated with elevated plasma levels of high-sensitivity C-reactive protein in the early phase of myocardial infarction. Tohoku J Exp Med 221:107–112CrossRefGoogle Scholar
  19. 19.
    Broeckel U et al (2002) A comprehensive linkage analysis for myocardial infarction and its related risk factors. Nat Gen 30:210–214.  https://doi.org/10.1038/ng827 CrossRefGoogle Scholar
  20. 20.
    Yamada Y et al (2002) Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med 347:1916–1923.  https://doi.org/10.1056/NEJMoa021445 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Hvidtfeldt UA et al (2010) Alcohol intake and risk of coronary heart disease in younger, middle-aged, and older adults. Circulation 121:1589–1597.  https://doi.org/10.1161/circulationaha.109.887513 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Huang B et al (2012) Adverse cardiovascular effects of concomitant use of proton pump inhibitors and clopidogrel in patients with coronary artery disease: a systematic review and meta-analysis. Arch Med Res 43:212–224.  https://doi.org/10.1016/j.arcmed.2012.04.004 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Edenberg HJ (2007) The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Res Health 30:5–13PubMedPubMedCentralGoogle Scholar
  24. 24.
    Li Y et al (2006) Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin. J Clin Invest 116:506–511.  https://doi.org/10.1172/JCI26564 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Eng MY, Luczak SE, Wall TL (2007) ALDH2, ADH1B, and ADH1C genotypes in Asians: a literature review. Alcohol Res Health 30:22–27PubMedPubMedCentralGoogle Scholar
  26. 26.
    Isse T, Matsuno K, Oyama T, Kitagawa K, Kawamoto T (2005) Aldehyde dehydrogenase 2 gene targeting mouse lacking enzyme activity shows high acetaldehyde level in blood, brain, and liver after ethanol gavages. Alcohol Clin Exp Res 29:1959–1964CrossRefGoogle Scholar
  27. 27.
    Xu F et al (2007) The polymorphism in acetaldehyde dehydrogenase 2 gene, causing a substitution of Glu > Lys (504), is not associated with coronary atherosclerosis severity in Han Chinese. Tohoku J Exp Med 213:215–220CrossRefGoogle Scholar
  28. 28.
    Han H et al (2013) Association of genetic polymorphisms in ADH and ALDH2 with risk of coronary artery disease and myocardial infarction: a meta-analysis. Gene 526:134–141.  https://doi.org/10.1016/j.gene.2013.05.002 CrossRefGoogle Scholar
  29. 29.
    Fernandez E et al (2006) Monoamine metabolism and behavioral responses to ethanol in mitochondrial aldehyde dehydrogenase knockout mice. Alcohol Clin Exp Res 30:1650–1658.  https://doi.org/10.1111/j.1530-0277.2006.00200.x CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Parker JD, Parker JO (1998) Nitrate therapy for stable angina pectoris. N Engl J Med 338:520–531.  https://doi.org/10.1056/NEJM199802193380807 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Chen Z et al (2005) An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin bioactivation. Proc Natl Acad Sci U S A 102:12159–12164.  https://doi.org/10.1073/pnas.0503723102 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Ferreira JC, Mochly-Rosen D (2012) Nitroglycerin use in myocardial infarction patients. Circ J 76:15–21CrossRefGoogle Scholar
  33. 33.
    Guo R et al (2008) Evidence for involvement of calcitonin gene-related peptide in nitroglycerin response and association with mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism. J Am Coll Cardiol 52:953–960.  https://doi.org/10.1016/j.jacc.2008.05.049 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Zhang H et al (2007) The relationship between aldehyde dehydrogenase-2 gene polymorphisms and efficacy of nitroglycerin. Zhonghua Nei Ke Za Zhi 46:629–632PubMedPubMedCentralGoogle Scholar
  35. 35.
    Chen CH et al (2008) Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science 321:1493–1495.  https://doi.org/10.1126/science.1158554 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Sun A et al (2014) Aldehyde dehydrogenase 2 ameliorates doxorubicin-induced myocardial dysfunction through detoxification of 4-HNE and suppression of autophagy. J Mol Cell Cardiol 71:92–104.  https://doi.org/10.1016/j.yjmcc.2014.01.002 CrossRefGoogle Scholar
  37. 37.
    Goedde HW et al (1983) Population genetic studies on aldehyde dehydrogenase isozyme deficiency and alcohol sensitivity. Am J Human Gen 35:769–772Google Scholar
  38. 38.
    Hoshi H et al (2012) Aldehyde-stress resulting from Aldh2 mutation promotes osteoporosis due to impaired osteoblastogenesis. J Bone Miner Res 27:2015–2023.  https://doi.org/10.1002/jbmr.1634 CrossRefGoogle Scholar
  39. 39.
    Doser TA et al (2009) Transgenic overexpression of aldehyde dehydrogenase-2 rescues chronic alcohol intake-induced myocardial hypertrophy and contractile dysfunction. Circulation 119:1941–1194.  https://doi.org/10.1161/CIRCULATIONAHA.108.823799 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Ge W, Guo R, Ren J (2011) AMP-dependent kinase and autophagic flux are involved in aldehyde dehydrogenase-2-induced protection against cardiac toxicity of ethanol. Free Radic Biol Med 51:1736–1748.  https://doi.org/10.1016/j.freeradbiomed.2011.08.002 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Ge W, Ren J (2012) mTOR-STAT3-notch signalling contributes to ALDH2-induced protection against cardiac contractile dysfunction and autophagy under alcoholism. J Cell Mol Med 16:616–626.  https://doi.org/10.1111/j.1582-4934.2011.01347.x CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Kim J, Chen CH, Yang J, Mochly-Rosen D (2017) Aldehyde dehydrogenase 2*2 knock-in mice show increased reactive oxygen species production in response to cisplatin treatment. J Biomed Sci 24:33.  https://doi.org/10.1186/s12929-017-0338-8 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Churchill EN, Disatnik MH, Mochly-Rosen D (2009) Time-dependent and ethanol-induced cardiac protection from ischemia mediated by mitochondrial translocation of varepsilonPKC and activation of aldehyde dehydrogenase 2. J Mol Cell Cardiol 46:278–284.  https://doi.org/10.1016/j.yjmcc.2008.09.713 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Ebert AD et al (2014) Characterization of the molecular mechanisms underlying increased ischemic damage in the aldehyde dehydrogenase 2 genetic polymorphism using a human induced pluripotent stem cell model system. Sci Transl Med 6:255 ra130.  https://doi.org/10.1126/scitranslmed.3009027 CrossRefGoogle Scholar
  45. 45.
    Sun A et al (2014) Mitochondrial aldehyde dehydrogenase 2 plays protective roles in heart failure after myocardial infarction via suppression of the cytosolic JNK/p53 pathway in mice. J Am Heart Assoc 3:e000779.  https://doi.org/10.1161/JAHA.113.000779 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Cooper C, Campion G, Melton L (1992) J., 3rd. Hip fractures in the elderly: a world-wide projection. Osteoporos Int 2:285–289CrossRefGoogle Scholar
  47. 47.
    Cui L et al (2010) Sublethal total body irradiation leads to early cerebellar damage and oxidative stress. Curr Neurovasc Res 7:125–135CrossRefGoogle Scholar
  48. 48.
    Dandre F, Cassaigne A, Iron A (1995) The frequency of the mitochondrial aldehyde dehydrogenase I2 (atypical) allele in Caucasian, oriental and African black populations determined by the restriction profile of PCR-amplified DNA. Mol Cell Probes 9:189–193.  https://doi.org/10.1006/mcpr.1995.0030 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Ma H, Guo R, Yu L, Zhang Y, Ren J (2011) Aldehyde dehydrogenase 2 (ALDH2) rescues myocardial ischaemia/reperfusion injury: role of autophagy paradox and toxic aldehyde. Eur Heart J 32:1025–1038.  https://doi.org/10.1093/eurheartj/ehq253 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Becker LB (2004) New concepts in reactive oxygen species and cardiovascular reperfusion physiology. Cardiovasc Res 61:461–470.  https://doi.org/10.1016/j.cardiores.2003.10.025 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Gong D et al (2012) Aldehyde dehydrogenase-2 activation during cardioplegic arrest enhances the cardioprotection against myocardial ischemia-reperfusion injury. Cardiovasc Toxicol 12:350–358.  https://doi.org/10.1007/s12012-012-9179-6 CrossRefGoogle Scholar
  52. 52.
    Ohsawa I et al (2008) Age-dependent neurodegeneration accompanying memory loss in transgenic mice defective in mitochondrial aldehyde dehydrogenase 2 activity. J Neurosci 28:6239–6249.  https://doi.org/10.1523/JNEUROSCI.4956-07 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Yu BP (2005) Membrane alteration as a basis of aging and the protective effects of calorie restriction. Mech Ageing Dev 126:1003–1010.  https://doi.org/10.1016/j.mad.2005.03.020 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Ota H et al (2006) Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene 25:176–185.  https://doi.org/10.1038/sj.onc.1209049 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Wu B et al (2016) Aldehyde dehydrogenase 2 activation in aged heart improves the autophagy by reducing the carbonyl modification on SIRT1. Oncotarget 7:2175–2188.  https://doi.org/10.18632/oncotarget.6814 CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Gu C et al (2013) Impaired cardiac SIRT1 activity by carbonyl stress contributes to aging-related ischemic intolerance. PLoS One 8:e74050.  https://doi.org/10.1371/journal.pone.0074050 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    McBeth J et al (2009) Musculoskeletal pain is associated with a long-term increased risk of cancer and cardiovascular-related mortality. Rheumatology 48:74–77.  https://doi.org/10.1093/rheumatology/ken424 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Li C et al (2018) Targeting ALDH2 for therapeutic interventions in chronic pain-related myocardial ischemic susceptibility. Theranostics 8:1027–1041.  https://doi.org/10.7150/thno.22414 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Kang PF et al (2016) Activation of ALDH2 with low concentration of ethanol attenuates myocardial ischemia/reperfusion injury in diabetes rat model. Oxidative Med Cell Longev 2016:6190504.  https://doi.org/10.1155/2016/6190504 CrossRefGoogle Scholar
  60. 60.
    Roger VL et al (2011) Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation 123:e18–e209.  https://doi.org/10.1161/CIR.0b013e3182009701 CrossRefGoogle Scholar
  61. 61.
    Fukai M et al (2005) Lipid peroxidation during ischemia depends on ischemia time in warm ischemia and reperfusion of rat liver. Free Radic Biol Med 38:1372–1381.  https://doi.org/10.1016/j.freeradbiomed.2005.02.004 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Farout L, Mary J, Vinh J, Szweda LI, Friguet B (2006) Inactivation of the proteasome by 4-hydroxy-2-nonenal is site specific and dependant on 20S proteasome subtypes. Arch Biochem Biophys 453:135–142.  https://doi.org/10.1016/j.abb.2006.02.003 CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Chen J, Henderson GI, Freeman GL (2001) Role of 4-hydroxynonenal in modification of cytochrome c oxidase in ischemia/reperfused rat heart. J Mol Cell Cardiol 33:1919–1927.  https://doi.org/10.1006/jmcc.2001.1454 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Lucas DT, Szweda LI (1999) Declines in mitochondrial respiration during cardiac reperfusion: age-dependent inactivation of alpha-ketoglutarate dehydrogenase. Proc Natl Acad Sci U S A 96:6689–6693CrossRefGoogle Scholar
  65. 65.
    Bhatnagar A (2006) Environmental cardiology: studying mechanistic links between pollution and heart disease. Circ Res 99:692–705.  https://doi.org/10.1161/01.RES.0000243586.99701.cf CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Luo J et al (2007) Mechanisms of acrolein-induced myocardial dysfunction: implications for environmental and endogenous aldehyde exposure. Am J Physiol Heart Circ Physiol 293:H3673–H3684.  https://doi.org/10.1152/ajpheart.00284.2007 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Bellamy CA, Nicely B, Mattice BJ, Teaster R (2008) Comparative analysis of clinical efficacy and cost between University of Wisconsin solution and histidine-tryptophan-ketoglutarate. Prog Transplant 18:166–171CrossRefGoogle Scholar
  68. 68.
    Zhang H, Gong DX, Zhang YJ, Li SJ, Hu S (2012) Effect of mitochondrial aldehyde dehydrogenase-2 genotype on cardioprotection in patients with congenital heart disease. Eur Heart J 33:1606–1614.  https://doi.org/10.1093/eurheartj/ehs061 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Luckey SW, Tjalkens RB, Petersen DR (1999) Mechanism of inhibition of rat liver class 2 ALDH by 4-hydroxynonenal. Adv Exp Med Biol 463:71–77CrossRefGoogle Scholar
  70. 70.
    Petersen DR, Doorn JA (2004) Reactions of 4-hydroxynonenal with proteins and cellular targets. Free Radic Biol Med 37:937–945.  https://doi.org/10.1016/j.freeradbiomed.2004.06.012 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Brooks PJ, Enoch MA, Goldman D, Li TK, Yokoyama A (2009) The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption. PLoS Med 6:e50.  https://doi.org/10.1371/journal.pmed.1000050 CrossRefPubMedGoogle Scholar
  72. 72.
    Enomoto N, Takase S, Yasuhara M, Takada A (1991) Acetaldehyde metabolism in different aldehyde dehydrogenase-2 genotypes. Alcohol Clin Exp Res 15:141–144CrossRefGoogle Scholar
  73. 73.
    Endo J et al (2009) Metabolic remodeling induced by mitochondrial aldehyde stress stimulates tolerance to oxidative stress in the heart. Circ Res 105:1118–1127.  https://doi.org/10.1161/CIRCRESAHA.109.206607 CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Weyker PD, Webb CA, Kiamanesh D, Flynn BC (2013) Lung ischemia reperfusion injury: a bench-to-bedside review. Semin Cardiothorac Vasc Anesth 17:28–43.  https://doi.org/10.1177/1089253212458329 CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Apostolakis E, Filos KS, Koletsis E, Dougenis D (2010) Lung dysfunction following cardiopulmonary bypass. J Card Surg 25:47–55.  https://doi.org/10.1111/j.1540-8191.2009.00823.x CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Schlensak C et al (2001) Bronchial artery perfusion during cardiopulmonary bypass does not prevent ischemia of the lung in piglets: assessment of bronchial artery blood flow with fluorescent microspheres. Eur J Cardiothorac Surg 19:326–331CrossRefGoogle Scholar
  77. 77.
    Apostolakis EE, Koletsis EN, Baikoussis NG, Siminelakis SN, Papadopoulos GS (2010) Strategies to prevent intraoperative lung injury during cardiopulmonary bypass. J Cardiothorac Surg 5:1.  https://doi.org/10.1186/1749-8090-5-1 CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Yoon M, Madden MC, Barton HA (2006) Developmental expression of aldehyde dehydrogenase in rat: a comparison of liver and lung development. Toxicol Sci 89:386–398.  https://doi.org/10.1093/toxsci/kfj045 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Stewart MJ, Malek K, Crabb DW (1996) Distribution of messenger RNAs for aldehyde dehydrogenase 1, aldehyde dehydrogenase 2, and aldehyde dehydrogenase 5 in human tissues. J Investig Med 44:42–46Google Scholar
  80. 80.
    Ding J et al (2016) Alda-1 attenuates lung ischemia-reperfusion injury by reducing 4-Hydroxy-2-Nonenal in alveolar epithelial cells. Crit Care Med 44:e544–e552.  https://doi.org/10.1097/CCM.0000000000001563 CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Lin YP, Cheng TJ (2002) Why can’t Chinese Han drink alcohol? Hepatitis B virus infection and the evolution of acetaldehyde dehydrogenase deficiency. Med Hypotheses 59:204–207CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Cardiovascular Disease, Anesthesia Department, Fuwai Hospital, National Center for Cardiovascular DiseasesChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
  2. 2.Department of Physiology and PathophysiologyFourth Military Medical UniversityXi’anChina
  3. 3.Heart Center and Shanghai Institution of Pediatric Congenital Heart Disease, Shanghai Children’s Medical Center, National Children’s Medical Center, Shanghai Jiaotong University School of MedlineShanghaiChina

Personalised recommendations