Archives of Toxicology

, Volume 92, Issue 4, pp 1563–1579 | Cite as

Maternal NO2 exposure induces cardiac hypertrophy in male offspring via ROS-HIF-1α transcriptional regulation and aberrant DNA methylation modification of Csx/Nkx2.5

Reproductive Toxicology
  • 121 Downloads

Abstract

Maternal exposure to nitrogen dioxide (NO2) poses a risk for morbidity and mortality in infantile congenital heart diseases and even adult cardiovascular diseases. However, the experimental evidence supporting these effects is insufficient, and the related regulatory mechanisms are unknown. In the present study, we aimed to determine whether maternal NO2 exposure causes cardiac hypertrophy-related consequences in offspring, and if so, how these adverse effects occur in the postnatal heart. The results indicate that in mice, maternal NO2 exposure causes cardiac hypertrophy in male offspring. This altered phenotype was accompanied by increased expression of atrial natriuretic peptide, B-type natriuretic peptide, bone morphogenetic protein 10 and β-myosin heavy chain and elevated activities of cardiomyocyte injury markers, including serum glutamate-oxaloacetate transaminase, lactate dehydrogenase and kinases creatine phosphokinase (CK-MB) in serum. The cardiac-specific transcription factor Csx/Nkx2.5 played an important role in the induction of cardiac hypertrophy and cardiomyocyte injury, and the action was associated with ROS-HIF-1α transcriptional regulation and DNA hypomethylation modification.

Keywords

Maternal NO2 exposure Cardiac hypertrophy Csx/Nkx2.5 ROS-HIF-1α transcriptional regulation DNA hypomethylation modification 

Notes

Acknowledgements

This study was supported by National Science Foundation of PR China (NSFC, No. 21377076, 21477070, 91543203, 21222701), Research Project for Young Sanjin Scholarship of Shanxi, Program for the Outstanding Innovative Teams of Higher Learning Institutions of Shanxi, and Research Project Supported by Shanxi Scholarship Council of China (No. 2015-006).

Compliance with ethical standards

Conflict of interest

The authors have no conflicts to disclose.

Supplementary material

204_2018_2166_MOESM1_ESM.doc (506 kb)
Supplementary material 1 (DOC 506 KB)

References

  1. Akazawa H, Komuro I (2003) Roles of cardiac transcription factors in cardiac hypertrophy. Circ Res 92(10):1079–1088CrossRefPubMedGoogle Scholar
  2. Akazawa H, Kudoh S, Mochizuki N, Takekoshi N, Takano H, Nagai T, Komuro I (2004) A novel LIM protein Cal promotes cardiac differentiation by association with CSX/NKX2-5. J Cell Biol 164(3):395–405CrossRefPubMedPubMedCentralGoogle Scholar
  3. Al-Attas OS, Hussain T, Ahmed M, Al-Daghri N, Mohammed AA, De Rosas E, Gambhir D, Sumague TS (2015) Ultrastructural changes, increased oxidative stress, inflammation, and altered cardiac hypertrophic gene expressions in heart tissues of rats exposed to incense smoke. Environ Sci Pollut Res Int 22(13):10083–10093CrossRefPubMedGoogle Scholar
  4. Aragon AC, Goens MB, Carbett E, Walker MK (2008) Perinatal 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure sensitizes offspring to angiotensin II-induced hypertension. Cardiovasc Toxicol 8(3):145–154CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bansal M, Kaushal N (2014) Oxidative stress mechanisms and their modulation. Springer, IndiaCrossRefGoogle Scholar
  6. Bär H, Kreuzer J, Cojoc A, Jahn L (2003) Upregulation of embryonic transcription factors in right ventricular hypertrophy. Basic Res Cardiol 98(5):285–294CrossRefPubMedGoogle Scholar
  7. Barker DJ (2007) The origins of the developmental origins theory. J Intern Med 261(5):412–417CrossRefPubMedGoogle Scholar
  8. Buscariollo DL, Fang X, Greenwood V, Xue H, Rivkees SA, Wendler CC (2014) Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice. PLoS One 9(1):e87547CrossRefPubMedPubMedCentralGoogle Scholar
  9. Carlson C, Koonce C, Aoyama N, Einhorn S, Fiene S, Thompson A, Swanson B, Anson B, Kattman S (2013) Phenotypic screening with human iPS cell-derived cardiomyocytes: HTS-compatible assays for interrogating cardiac hypertrophy. J Biomol Screen 18(10):1203–1211CrossRefPubMedGoogle Scholar
  10. Chapalamadugu KC, Vandevoort CA, Settles ML, Robison BD, Murdoch GK (2014) Maternal bisphenol a exposure impacts the fetal heart transcriptome. PLoS One 9(2):e89096CrossRefPubMedPubMedCentralGoogle Scholar
  11. Chiusolo M, Cadum E, Stafoggia M, Galassi C, Berti G, Faustini A, Bisanti L, Vigotti MA, Dessì MP, Cernigliaro A, Mallone S, Pacelli B, Minerba S, Simonato L, Forastiere F, EpiAir Collaborative Group (2011) Short-term effects of nitrogen dioxide on mortality and susceptibility factors in 10 Italian cities: the EpiAir study. Environ Health Perspect 119(9):1233–1238CrossRefPubMedPubMedCentralGoogle Scholar
  12. Chowdhury D, Tangutur AD, Khatua TN, Saxena P, Banerjee SK, Bhadra MP (2013) A proteomic view of isoproterenol induced cardiac hypertrophy: prohibitin identified as a potential biomarker in rats. J Transl Med 11:130CrossRefPubMedPubMedCentralGoogle Scholar
  13. Chu W, Wan L, Zhao D, Qu X, Cai F, Huo R, Wang N, Zhu J, Zhang C, Zheng F, Cai R, Dong D, Lu Y, Yang B (2012) Mild hypoxia-induced cardiomyocyte hypertrophy via up-regulation of HIF-1α-mediated TRPC signalling. J Cell Mol Med 16(9):2022–2034CrossRefPubMedPubMedCentralGoogle Scholar
  14. Chung IM, Rajakumar G (2016) Genetics of congenital heart defects: the NKX2-5 gene, a key player. Genes (Basel) 7(2)Google Scholar
  15. Dadvand P, Rankin J, Rushton S, Pless-Mulloli T (2011) Ambient air pollution and congenital heart disease: a register-based study. Environ Res 111(3):435–441CrossRefPubMedGoogle Scholar
  16. Dai H, Jia G, Liu X, Liu Z, Wang H (2014) Astragalus polysaccharide inhibits isoprenaline-induced cardiac hypertrophy via suppressing Ca2+-mediated calcineurin/NFATc3 and CaMKII signaling cascades. Environ Toxicol Pharmacol 38(1):263–271CrossRefPubMedGoogle Scholar
  17. Elnakish MT, Ahmed AA, Mohler PJ, Janssen PM (2015) Role of oxidative stress in thyroid hormone-induced cardiomyocyte hypertrophy and associated cardiac dysfunction: an undisclosed story. Oxid Med Cell Longev 2015:854265Google Scholar
  18. Feng Y, Zhao LZ, Hong L, Shan C, Shi W, Cai W (2013) Alteration in methylation pattern of GATA-4 promoter region in vitamin A-deficient offspring’s heart. J Nutr Biochem 24(7):1373–1380CrossRefPubMedGoogle Scholar
  19. Gallagher JM, Komati H, Roy E, Nemer M, Latinkić BV (2012) Dissociation of cardiogenic and postnatal myocardial activities of GATA4. Mol Cell Biol 32(12):2214–2223CrossRefPubMedPubMedCentralGoogle Scholar
  20. Hahn NE, Musters RJ, Fritz JM, Pagano PJ, Vonk AB, Paulus WJ, van Rossum AC, Meischl C, Niessen HW, Krijnen PA (2014) Early NADPH oxidase-2 activation is crucial in phenylephrine-induced hypertrophy of H9c2 cells. Cell Signal 26(9):1818–1824CrossRefPubMedPubMedCentralGoogle Scholar
  21. Han SS, Wang G, Jin Y, Ma ZL, Jia WJ, Wu X, Wang XY, He MY, Cheng X, Li WJ, Yang X, Liu GS (2015) Investigating the mechanism of hyperglycemia-induced fetal cardiac hypertrophy. PLoS One 10(9):e0139141CrossRefPubMedPubMedCentralGoogle Scholar
  22. Hang CT, Yang J, Han P, Cheng HL, Shang C, Ashley E, Zhou B, Chang CP (2010) Chromatin regulation by Brg1 underlies heart muscle development and disease. Nature 466(7302):62–67CrossRefPubMedPubMedCentralGoogle Scholar
  23. Hettfleisch K, Bernardes LS, Carvalho MA, Pastro LD, Vieira SE, Saldiva SR, Saldiva P, Francisco RP (2017) Short-term exposure to urban air pollution and influences on placental vascularization indexes. Environ Health Perspect 125(4):753–759PubMedGoogle Scholar
  24. Hiroi Y, Kudoh S, Monzen K, Ikeda Y, Yazaki Y, Nagai R, Komuro I (2001) Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation. Nat Genet 28(3):276–280CrossRefPubMedGoogle Scholar
  25. Huang ZP, Chen J, Seok HY, Zhang Z, Kataoka M, Hu X, Wang DZ (2013) MicroRNA-22 regulates cardiac hypertrophy and remodeling in response to stress. Circ Res 112(9):1234–1243CrossRefPubMedPubMedCentralGoogle Scholar
  26. Huang L, Gao D, Zhang Y, Wang C, Zuo Z (2014) Exposure to low dose benzo[a]pyrene during early life stages causes symptoms similar to cardiac hypertrophy in adult zebrafish. J Hazard Mater 276:377–382CrossRefPubMedGoogle Scholar
  27. Huang L, Xi Z, Wang C, Zhang Y, Yang Z, Zhang S, Chen Y, Zuo Z (2016) Phenanthrene exposure induces cardiac hypertrophy via reducing miR-133a expression by DNA methylation. Sci Rep 6:20105CrossRefPubMedPubMedCentralGoogle Scholar
  28. Ji X, Han M, Yun Y, Li G, Sang N (2015) Acute nitrogen dioxide (NO2) exposure enhances airway inflammation via modulating Th1/Th2 differentiation and activating JAK-STAT pathway. Chemosphere 120:722–728CrossRefPubMedGoogle Scholar
  29. Ji X, Ku T, Zhu N, Ning X, Wei W, Li G, Sang N (2016) Potential hepatic toxicity of buprofezin at sublethal concentrations: ROS-mediated conversion of energy metabolism. J Hazard Mater 320:176–186CrossRefPubMedGoogle Scholar
  30. Kaur M, Tappia PS (2009) Metabolic shifts during cardiac hypertrophy. Clin Lipidol 4(6):725–729CrossRefGoogle Scholar
  31. Khatua TN, Borkar RM, Mohammed SA, Dinda AK, Srinivas R, Banerjee SK (2017) Novel sulfur metabolites of garlic attenuate cardiac hypertrophy and remodeling through induction of Na+/K+-ATPase expression. Front Pharmacol 8:18CrossRefPubMedPubMedCentralGoogle Scholar
  32. Kietzmann T, Görlach A (2005) Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression. Semin Cell Dev Biol 16(4–5):474–486CrossRefPubMedGoogle Scholar
  33. Krishnan J, Ahuja P, Bodenmann S, Knapik D, Perriard E, Krek W, Perriard JC (2008) Essential role of developmentally activated hypoxia-inducible factor 1alpha for cardiac morphogenesis and function. Circ Res 103(10):1139–1146CrossRefPubMedGoogle Scholar
  34. La Merrill MA, Sethi S, Benard L, Moshier E, Haraldsson B, Buettner C (2016) Perinatal DDT exposure induces hypertension and cardiac hypertrophy in adult mice. Environ Health Perspect 124(11):1722–1727CrossRefPubMedPubMedCentralGoogle Scholar
  35. Laskowski A, Woodman OL, Cao AH, Drummond GR, Marshall T, Kaye DM, Ritchie RH (2006) Antioxidant actions contribute to the antihypertrophic effects of atrial natriuretic peptide in neonatal rat cardiomyocytes. Cardiovasc Res 72(1):112–123CrossRefPubMedGoogle Scholar
  36. Lee JW, Jaffar Z, Pinkerton KE, Porter V, Postma B, Ferrini M, Holian A, Roberts K, Cho YH (2015) Alterations in DNA methylation and airway hyperreactivity in response to in utero exposure to environmental tobacco smoke. Inhal Toxicol 27(13):724–730CrossRefPubMedPubMedCentralGoogle Scholar
  37. Leinwand LA (2001) Calcineurin inhibition and cardiac hypertrophy: a matter of balance. Proc Natl Acad Sci U S A 98(6):2947–2949CrossRefPubMedPubMedCentralGoogle Scholar
  38. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP (1990) Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 322(22):1561–1566CrossRefPubMedGoogle Scholar
  39. Li L, Zhang Y, Li Y, Yu B, Xu Y, Zhao S, Guan Z (2008) Mesenchymal stem cell transplantation attenuates cardiac fibrosis associated with isoproterenol-induced global heart failure. Transpl Int 21(12):1181–1189CrossRefPubMedGoogle Scholar
  40. Li H, Han M, Guo L, Li G, Sang N (2011) Oxidative stress, endothelial dysfunction and inflammatory response in rat heart to NO2 inhalation exposure. Chemosphere 82(11):1589–1596CrossRefPubMedGoogle Scholar
  41. Liang Q, Molkentin JD (2002) Divergent signaling pathways converge on GATA4 to regulate cardiac hypertrophic gene expression. J Mol Cell Cardiol 34(6):611–616CrossRefPubMedGoogle Scholar
  42. Liao XH, Wang N, Liu QX, Qin T, Cao B, Cao DS, Zhang TC (2011) Myocardin-related transcription factor-A induces cardiomyocyte hypertrophy. IUBMB Life 63(1):54–61CrossRefPubMedGoogle Scholar
  43. Liu JC, Chan P, Chen JJ, Lee HM, Lee WS, Shih NL, Chen YL, Hong HJ, Cheng TH (2004) The inhibitory effect of trilinolein on norepinephrine-induced beta-myosin heavy chain promoter activity, reactive oxygen species generation, and extracellular signal-regulated kinase phosphorylation in neonatal rat cardiomyocytes. J Biomed Sci 11(1):11–18PubMedGoogle Scholar
  44. Lorell BH, Carabello BA (2000) Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation 102(4):470–479CrossRefPubMedGoogle Scholar
  45. Luo K, Li R, Li W, Wang Z, Ma X, Zhang R, Fang X, Wu Z, Cao Y, Xu Q (2016) Acute effects of nitrogen dioxide on cardiovascular mortality in beijing: an exploration of spatial heterogeneity and the district-specific predictors. Sci Rep 6:38328CrossRefPubMedPubMedCentralGoogle Scholar
  46. Maulik SK, Kumar S (2012) Oxidative stress and cardiac hypertrophy: a review. Toxicol Mech Methods 22(5):359–366CrossRefPubMedGoogle Scholar
  47. McCulley DJ, Black BL (2012) Transcription factor pathways and congenital heart disease. Curr Top Dev Biol 100:253–277CrossRefPubMedPubMedCentralGoogle Scholar
  48. Molkentin JD (2000) The zinc finger-containing transcription factors GATA-4, -5, and -6. Ubiquitously expressed regulators of tissue-specific gene expression. J Biol Chem 275(50):38949–38952CrossRefPubMedGoogle Scholar
  49. Molkentin JD (2004) Calcineurin-NFAT signaling regulates the cardiac hypertrophic response in coordination with the MAPKs. Cardiovasc Res 63(3):467–475CrossRefPubMedGoogle Scholar
  50. Nagao K, Taniyama Y, Kietzmann T, Doi T, Komuro I, Morishita R (2008) HIF-1α signaling upstream of NKX2.5 is required for cardiac development in Xenopus. J Biol Chem 283(17):11841–11849CrossRefPubMedGoogle Scholar
  51. Nakashima Y, Ono K, Yoshida Y, Kojima Y, Kita T, Kimura T (2009) Abstract 1919: the identification of the Nkx2-5-regulated genes using purified ES cell-derived cardiomyocytes. Circulation 120:S571Google Scholar
  52. Pashmforoush M, Lu JT, Chen H, Amand TS, Kondo R, Pradervand S, Evans SM, Clark B, Feramisco JR, Giles W, Ho SY, Benson DW, Silberbach M, Shou W, Chien KR (2004) Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block. Cell 117(3):373–386CrossRefPubMedGoogle Scholar
  53. Peng C, Zhang W, Zhao W, Zhu J, Huang X, Tian J (2015) Alcohol-induced histone H3K9 hyperacetylation and cardiac hypertrophy are reversed by a histone acetylases inhibitor anacardic acid in developing murine hearts. Biochimie 113:1–9CrossRefPubMedGoogle Scholar
  54. Philippen LE, Dirkx E, da Costa-Martins PA, De Windt LJ (2015) Non-coding RNA in control of gene regulatory programs in cardiac development and disease. J Mol Cell Cardiol 89(Pt A):51–58CrossRefPubMedGoogle Scholar
  55. Prathapan A, Varghese MV, Abhilash S, Salin Raj P, Mathew AK, Nair A, Nair RH, Raghu KG (2017) Polyphenol rich ethanolic extract from Boerhavia diffusa L. mitigates angiotensin II induced cardiac hypertrophy and fibrosis in rats. Biomed Pharmacother 87:427–436CrossRefGoogle Scholar
  56. Qin L, Xifa S, Dawei X, Yangjing X, Kangting J, Jian X, Suqin Z (2016) Role of hypoxia-inducible factor in diabetic myocardial hypertrophy. Trop J Pharm Res 15(11):2421–2427CrossRefGoogle Scholar
  57. Sang N, Yun Y, Yao GY, Li HY, Guo L, Li GK (2011) SO(2)-induced neurotoxicity is mediated by cyclooxygenases-2-derived prostaglandin E(2) and its downstream signaling pathway in rat hippocampal neurons. Toxicol Sci 124(2):400–413CrossRefPubMedGoogle Scholar
  58. Seddon M, Looi YH, Shah AM (2007) Oxidative stress and redox signalling in cardiac hypertrophy and heart failure. Heart 93(8):903–907CrossRefPubMedGoogle Scholar
  59. Serra-Juhé C, Cuscó I, Homs A, Flores R, Torán N, Pérez-Jurado LA (2015) DNA methylation abnormalities in congenital heart disease. Epigenetics 10(2):167–177CrossRefPubMedPubMedCentralGoogle Scholar
  60. Sheng W, Qian Y, Wang H, Ma X, Zhang P, Diao L, An Q, Chen L, Ma D, Huang G (2013) DNA methylation status of NKX2-5, GATA4 and HAND1 in patients with tetralogy of fallot. BMC Med Genomics 6:46CrossRefPubMedPubMedCentralGoogle Scholar
  61. Song XW, Li Q, Lin L, Wang XC, Li DF, Wang GK, Ren AJ, Wang YR, Qin YW, Yuan WJ, Jing Q (2010) MicroRNAs are dynamically regulated in hypertrophic hearts, and miR-199a is essential for the maintenance of cell size in cardiomyocytes. J Cell Physiol 225(2):437–443CrossRefPubMedGoogle Scholar
  62. Stenzig J, Hirt MN, Löser A, Bartholdt LM, Hensel JT, Werner TR, Riemenschneider M, Indenbirken D, Guenther T, Müller C, Hübner N, Stoll M, Eschenhagen T (2016) DNA methylation in an engineered heart tissue model of cardiac hypertrophy: common signatures and effects of DNA methylation inhibitors. Basic Res Cardiol 111(1):9CrossRefPubMedGoogle Scholar
  63. Stingone JA, Luben TJ, Daniels JL, Fuentes M, Richardson DB, Aylsworth AS, Herring AH, Anderka M, Botto L, Correa A, Gilboa SM, Langlois PH, Mosley B, Shaw GM, Siffel C, Olshan AF, National Birth Defects Prevention Study (2014) Maternal exposure to criteria air pollutants and congenital heart defects in offspring: results from the national birth defects prevention study. Environ Health Perspect 122(8):863–872PubMedPubMedCentralGoogle Scholar
  64. Sun SQ, Wang XT, Qu XF, Li Y, Yu Y, Song Y, Wang SJ (2011) Increased expression of myocardial semaphorin 3A in isoproterenol-induced heart failure rats. Chin Med J (Engl) 124(14):2173–2178Google Scholar
  65. Takeda M, Briggs LE, Wakimoto H, Marks MH, Warren SA, Lu JT, Weinberg EO, Robertson KD, Chien KR, Kasahara H (2009) Slow progressive conduction and contraction defects in loss of Nkx2-5 mice after cardiomyocyte terminal differentiation. Lab Invest 89(9):983–993CrossRefPubMedPubMedCentralGoogle Scholar
  66. Takimoto E, Kass DA (2007) Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension 49(2):241–248CrossRefPubMedGoogle Scholar
  67. Takimoto E, Mizuno T, Terasaki F, Shimoyama M, Honda H, Shiojima I, Hiroi Y, Oka T, Hayashi D, Hirai H, Kudoh S, Toko H, Kawamura K, Nagai R, Yazaki Y, Komuro I (2000) Up-regulation of natriuretic peptides in the ventricle of Csx/Nkx2-5 transgenic mice. Biochem Biophys Res Commun 270(3):1074–1079CrossRefPubMedGoogle Scholar
  68. Tham YK, Bernardo BC, Ooi JY, Weeks KL, McMullen JR (2015) Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets. Arch Toxicol 89(9):1401–1438CrossRefPubMedGoogle Scholar
  69. Vaupel P (2004) The role of hypoxia-induced factors in tumor progression. Oncologist 5:10–17CrossRefGoogle Scholar
  70. Wamstad JA, Alexander JM, Truty RM, Shrikumar A, Li F, Eilertson KE, Ding H, Wylie JN, Pico AR, Capra JA, Erwin G, Kattman SJ, Keller GM, Srivastava D, Levine SS, Pollard KS, Holloway AK, Boyer LA, Bruneau BG (2012) Dynamic and coordinated epigenetic regulation of developmental transitions in the cardiac lineage. Cell 151(1):206–220CrossRefPubMedPubMedCentralGoogle Scholar
  71. Wang Y, Tandan S, Hill JA (2014) Calcineurin-dependent ion channel regulation in heart. Trends Cardiovasc Med 24(1):14–22CrossRefPubMedGoogle Scholar
  72. Wang F, Wu Y, Quon MJ, Li X, Yang P (2015) ASK1 mediates the teratogenicity of diabetes in the developing heart by inducing ER stress and inhibiting critical factors essential for cardiac development. Am J Physiol Endocrinol Metab 309(5):E487-499CrossRefGoogle Scholar
  73. Warren SA, Terada R, Briggs LE, Cole-Jeffrey CT, Chien WM, Seki T, Weinberg EO, Yang TP, Chin MT, Bungert J, Kasahara H (2011) Differential role of Nkx2-5 in activation of the atrial natriuretic factor gene in the developing versus failing heart. Mol Cell Biol 31(22):4633–4645CrossRefPubMedPubMedCentralGoogle Scholar
  74. Wilkins BJ, Molkentin JD (2004) Calcium-calcineurin signaling in the regulation of cardiac hypertrophy. Biochem Biophys Res Commun 322(4):1178–1191CrossRefPubMedGoogle Scholar
  75. Xiao D, Dasgupta C, Chen M, Zhang K, Buchholz J, Xu Z, Zhang L (2014) Inhibition of DNA methylation reverses norepinephrine-induced cardiac hypertrophy in rats. Cardiovasc Res 101(3):373–382CrossRefPubMedGoogle Scholar
  76. Yan W, Yun Y, Ku T, Li G, Sang N (2016) NO2 inhalation promotes Alzheimer’s disease-like progression: cyclooxygenase-2-derived prostaglandin E2 modulation and monoacylglycerol lipase inhibition-targeted medication. Sci Rep 6 1:22429CrossRefGoogle Scholar
  77. Yang Q, Yang J, Wu G, Feng Y, Lv Q, Lin S, Hu J (2013) Effects of taurine on myocardial cGMP/cAMP ratio, antioxidant ability, and ultrastructure in cardiac hypertrophy rats induced by isoproterenol. Adv Exp Med Biol 776:217–229CrossRefPubMedGoogle Scholar
  78. Yilbas AE, Hamilton A, Wang Y, Mach H, Lacroix N, Davis DR, Chen J, Li Q (2014) Activation of GATA4 gene expression at the early stage of cardiac specification. Front Chem 2:12CrossRefPubMedPubMedCentralGoogle Scholar
  79. Yoshikawa N, Shimizu N, Ojima H, Kobayashi H, Hosono O, Tanaka H (2014) Down-regulation of hypoxia-inducible factor-1 alpha and vascular endothelial growth factor by HEXIM1 attenuates myocardial angiogenesis in hypoxic mice. Biochem Biophys Res Commun 453(3):600–605CrossRefPubMedGoogle Scholar
  80. Yue H, Yan W, Ji X, Gao R, Ma J, Rao Z, Li G, Sang N (2017) Maternal exposure of BALB/c mice to indoor NO2 and allergic asthma syndrome in offspring at adulthood with evaluation of DNA methylation associated Th2 polarization. Environ Health Perspect 125(9):097011CrossRefPubMedGoogle Scholar
  81. Zhou X, Zhang Q, Zhao T, Bai X, Yuan W, Wu Y, Liu D, Li S, Ju J, Chege Gitau S, Chu W, Xu C, Lu Y (2014) Cisapride protects against cardiac hypertrophy via inhibiting the up-regulation of calcineurin and NFATc-3. Eur J Pharmacol 735:202–210CrossRefPubMedGoogle Scholar
  82. Zhou W, Tian D, He J, Wang Y, Zhang L, Cui L, Jia L, Zhang L, Li L, Shu Y, Yu S, Zhao J, Yuan X, Peng S (2016) Repeated PM2.5 exposure inhibits BEAS-2B cell P53 expression through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation. Oncotarget 7(15):20691–20703PubMedPubMedCentralGoogle Scholar
  83. Zhu N, Li H, Han M, Guo L, Chen L, Yun Y, Guo Z, Li G, Sang N (2012) Environmental nitrogen dioxide (NO2) exposure influences development and progression of ischemic stroke. Toxicol Lett 214(2):120–130CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.College of Environment and Resource, Research Center of Environment and HealthShanxi UniversityTaiyuanPeople’s Republic of China

Personalised recommendations