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Basic Research in Cardiology

, 113:37 | Cite as

Activating transcription factor 3 in cardiovascular diseases: a potential therapeutic target

  • Heng Zhou
  • Ning Li
  • Yuan Yuan
  • Ya-Ge Jin
  • Haipeng Guo
  • Wei Deng
  • Qi-Zhu Tang
Review

Abstract

Cardiovascular diseases (CVDs) are the primary causes of death worldwide. Among the numerous signaling molecules involved in CVDs, transcriptional factors directly influence gene expression and play a critical role in regulating cell function and the development of diseases. Activating transcription factor (ATF) 3 is an adaptive-response gene in the ATF/cAMP responsive element-binding (CREB) protein family of transcription factors that acts as either a repressor or an activator of transcription via the formation of homodimers or heterodimers with other ATF/CREB members. A appropriate ATF3 expression is important for the normal physiology of cells, and dysfunction of ATF3 is associated with various pathophysiological responses such as inflammation, apoptosis, oxidative stress and endoplasmic reticulum stress, and diseases, including CVDs. This review focuses on the role of ATF3 in cardiac hypertrophy, heart failure, atherosclerosis, ischemic heart diseases, hypertension and diabetes mellitus to provide a novel therapeutic target for CVDs.

Keywords

Activating transcription factor 3 Cardiac hypertrophy Heart failure Atherosclerosis Cardiovascular diseases 

Abbreviations

ALK

Activin receptor-like kinase

Ang II

Angiotensin II

ATF

Activating transcription factor

bZIP

Basic-region leucine zipper

CRE

cAMP responsive element

CREB

cAMP responsive element binding

CVDs

Cardiovascular diseases

CXCL

C-X-C motif chemokine ligand

CXCR

C-X-C motif chemokine receptor

DM

Diabetes mellitus

DOX

Doxorubicin

ECs

Endothelial cells

EGFR

Epidermal growth factor receptor

Egr1

Early growth response protein 1

ERK

Extracellular signal-regulated kinase

ET-1

Endothelin-1

HDL

High-density lipoprotein

HF

Heart failure

HFD

High-fat diet

HUVECs

Human umbilical vein endothelial cells

ICAM

Intercellular cell adhesion molecule

IFNγ

Interferon γ

IHD

Ischemic heart diseases

IL

Interleukin

IP

Ischemic preconditioning

I/R

Ischemia/reperfusion

IRF7

Interferon regulatory factor 7

JNK

c-Jun N-terminal kinase

KLF

Krueppel-like factor

KO

Knockout

LPC

Lysophosphatidylcholine

LPS

Lipopolysaccharide

Map2K3

Mitogen-activated protein kinase kinase 3

MED

Methionine-enriched diet

MEK

MAPK/ERK kinase

MI

Myocardial infarction

MKK7

MAPK kinase 7

MMPs

Matrix metalloproteinases

NAFLD

Non-alcoholic fatty liver disease

NF-κB

Nuclear factor-κB

NO

Nitric oxide

oxLDL

Oxidized low-density lipoprotein

PCNA

Proliferating cell nuclear antigen

PE

Phenylephrine

PI3K

Phosphatidylinositol 3-kinase

PKA

Protein kinase A

SAPK

Stress-activated protein kinase

SMCs

Smooth muscle cells

tBHQ

tert-Butylhydroquinone

TGF-β

Transforming growth factor-β

TGRL

Triglyceride-rich lipoproteins

TLR

Toll-like receptor

TNF-α

Tumor necrosis factor-α

T2DM

Type 2 DM

VSMCs

Vascular smooth muscle cells

ZDF

Zucker Diabetic Fatty

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (81300070, 81770399, 81470516 and 81530012), the Fundamental Research Funds for the Central Universities of China (2042018kf0121), the Development Center for Medical Science and Technology National Health and Family Planning Commission of China (2016ZX-008-01), and the National Major Scientific Instrument and Equipment Development Projects of China (2013YQ03092306).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interests.

References

  1. 1.
    Aggarwal M, Aggarwal B, Rao J (2017) Integrative medicine for cardiovascular disease and prevention. Med Clin N Am 101:895–923.  https://doi.org/10.1016/j.mcna.2017.04.007 CrossRefPubMedGoogle Scholar
  2. 2.
    Akazawa H (2015) Mechanisms of cardiovascular homeostasis and pathophysiology—from gene expression, signal transduction to cellular communication. Circ J 79:2529–2536.  https://doi.org/10.1253/circj.CJ-15-0818 CrossRefPubMedGoogle Scholar
  3. 3.
    Altena R, Fehrmann RS, Boer H, de Vries EG, Meijer C, Gietema JA (2015) Growth differentiation factor 15 (GDF-15) plasma levels increase during bleomycin- and cisplatin-based treatment of testicular cancer patients and relate to endothelial damage. PLoS One 10:e0115372.  https://doi.org/10.1371/journal.pone.0115372 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Aung HH, Altman R, Nyunt T, Kim J, Nuthikattu S, Budamagunta M, Voss JC, Wilson D, Rutledge JC, Villablanca AC (2016) Lipotoxic brain microvascular injury is mediated by activating transcription factor 3-dependent inflammatory and oxidative stress pathways. J Lipid Res 57:955–968.  https://doi.org/10.1194/jlr.M061853 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Aung HH, Lame MW, Gohil K, An CI, Wilson DW, Rutledge JC (2013) Induction of ATF3 gene network by triglyceride-rich lipoprotein lipolysis products increases vascular apoptosis and inflammation. Arterioscler Thromb Vasc Biol 33:2088–2096.  https://doi.org/10.1161/ATVBAHA.113.301375 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Aung HH, Tsoukalas A, Rutledge JC, Tagkopoulos I (2014) A systems biology analysis of brain microvascular endothelial cell lipotoxicity. BMC Syst Biol 8:80.  https://doi.org/10.1186/1752-0509-8-80 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bauer AJ, Martin KA (2017) Coordinating regulation of gene expression in cardiovascular disease: interactions between chromatin modifiers and transcription factors. Front Cardiovasc Med 4:19.  https://doi.org/10.3389/fcvm.2017.00019 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Bentzon JF, Otsuka F, Virmani R, Falk E (2014) Mechanisms of plaque formation and rupture. Circ Res 114:1852–1866.  https://doi.org/10.1161/CIRCRESAHA.114.302721 CrossRefPubMedGoogle Scholar
  9. 9.
    Brooks AC, DeMartino AM, Brainard RE, Brittian KR, Bhatnagar A, Jones SP (2015) Induction of activating transcription factor 3 limits survival following infarct-induced heart failure in mice. Am J Physiol Heart Circ Physiol 309:H1326–H1335.  https://doi.org/10.1152/ajpheart.00513.2015 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Brooks AC, Guo Y, Singh M, McCracken J, Xuan YT, Srivastava S, Bolli R, Bhatnagar A (2014) Endoplasmic reticulum stress-dependent activation of ATF3 mediates the late phase of ischemic preconditioning. J Mol Cell Cardiol 76:138–147.  https://doi.org/10.1016/j.yjmcc.2014.08.011 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Cai Y, Zhang C, Nawa T, Aso T, Tanaka M, Oshiro S, Ichijo H, Kitajima S (2000) Homocysteine-responsive ATF3 gene expression in human vascular endothelial cells: activation of c-Jun NH(2)-terminal kinase and promoter response element. Blood 96:2140–2148PubMedGoogle Scholar
  12. 12.
    Chao HH, Hong HJ, Sung LC, Chen JJ, Cheng TH, Liu JC (2011) Nicorandil attenuates cyclic strain-induced endothelin-1 expression via the induction of activating transcription factor 3 in human umbilical vein endothelial cells. Eur J Pharmacol 667:292–297.  https://doi.org/10.1016/j.ejphar.2011.05.062 CrossRefPubMedGoogle Scholar
  13. 13.
    Chen HH, Wang DL (2004) Nitric oxide inhibits matrix metalloproteinase-2 expression via the induction of activating transcription factor 3 in endothelial cells. Mol Pharmacol 65:1130–1140.  https://doi.org/10.1124/mol.65.5.1130 CrossRefPubMedGoogle Scholar
  14. 14.
    Chen SC, Liu YC, Shyu KG, Wang DL (2008) Acute hypoxia to endothelial cells induces activating transcription factor 3 (ATF3) expression that is mediated via nitric oxide. Atherosclerosis 201:281–288.  https://doi.org/10.1016/j.atherosclerosis.2008.02.014 CrossRefPubMedGoogle Scholar
  15. 15.
    Chen YL, Tsai YT, Lee CY, Lee CH, Chen CY, Liu CM, Chen JJ, Loh SH, Tsai CS (2014) Urotensin II inhibits doxorubicin-induced human umbilical vein endothelial cell death by modulating ATF expression and via the ERK and Akt pathway. PLoS One 9:e106812.  https://doi.org/10.1371/journal.pone.0106812 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Clerk A, Cullingford TE, Fuller SJ, Giraldo A, Sugden PH (2009) Endothelin-1 regulation of immediate early gene expression in cardiac myocytes: negative feedback regulation of interleukin 6 by Atf3 and Klf2. Adv Enzyme Regul 49:30–42.  https://doi.org/10.1016/j.advenzreg.2008.12.007 CrossRefPubMedGoogle Scholar
  17. 17.
    De Nardo D, Labzin LI, Kono H, Seki R, Schmidt SV, Beyer M, Xu D, Zimmer S, Lahrmann C, Schildberg FA, Vogelhuber J, Kraut M, Ulas T, Kerksiek A, Krebs W, Bode N, Grebe A, Fitzgerald ML, Hernandez NJ, Williams BR, Knolle P, Kneilling M, Rocken M, Lutjohann D, Wright SD, Schultze JL, Latz E (2014) High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3. Nat Immunol 15:152–160.  https://doi.org/10.1038/ni.2784 CrossRefPubMedGoogle Scholar
  18. 18.
    Dong L, Krewson EA, Yang LV (2017) Acidosis activates endoplasmic reticulum stress pathways through gpr4 in human vascular endothelial cells. Int J Mol Sci.  https://doi.org/10.3390/ijms18020278 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Eiselein L, Nyunt T, Lame MW, Ng KF, Wilson DW, Rutledge JC, Aung HH (2015) TGRL lipolysis products induce stress protein ATF3 via the TGF-beta receptor pathway in human aortic endothelial cells. PLoS One 10:e0145523.  https://doi.org/10.1371/journal.pone.0145523 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ghigo A, Laffargue M, Li M, Hirsch E (2017) PI3K and Calcium Signaling in Cardiovascular Disease. Circ Res 121:282–292.  https://doi.org/10.1161/CIRCRESAHA.117.310183 CrossRefPubMedGoogle Scholar
  21. 21.
    Giraldo A, Barrett OP, Tindall MJ, Fuller SJ, Amirak E, Bhattacharya BS, Sugden PH, Clerk A (2012) Feedback regulation by Atf3 in the endothelin-1-responsive transcriptome of cardiomyocytes: Egr1 is a principal Atf3 target. Biochem J 444:343–355.  https://doi.org/10.1042/BJ20120125 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Hai T, Curran T (1991) Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity. Proc Natl Acad Sci USA 88:3720–3724CrossRefPubMedGoogle Scholar
  23. 23.
    Hai T, Hartman MG (2001) The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis. Gene 273:1–11 (S0378-1119(01)00551-0 [pii]) CrossRefPubMedGoogle Scholar
  24. 24.
    Hai T, Wolfgang CD, Marsee DK, Allen AE, Sivaprasad U (1999) ATF3 and stress responses. Gene Expr 7:321–335PubMedGoogle Scholar
  25. 25.
    Hai T, Wolford CC, Chang YS (2010) ATF3, a hub of the cellular adaptive-response network, in the pathogenesis of diseases: is modulation of inflammation a unifying component? Gene Expr 15:1–11CrossRefPubMedGoogle Scholar
  26. 26.
    Hai TW, Liu F, Coukos WJ, Green MR (1989) Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev 3:2083–2090CrossRefPubMedGoogle Scholar
  27. 27.
    Hasin T, Elhanani O, Abassi Z, Hai T, Aronheim A (2011) Angiotensin II signaling up-regulates the immediate early transcription factor ATF3 in the left but not the right atrium. Basic Res Cardiol 106:175–187.  https://doi.org/10.1007/s00395-010-0145-9 CrossRefPubMedGoogle Scholar
  28. 28.
    Heusch G (2017) Cardioprotection is alive but remains enigmatic: the nitric oxide-protein kinases-mitochondria signaling axis. Circulation 136:2356–2358.  https://doi.org/10.1161/CIRCULATIONAHA.117.031978 CrossRefPubMedGoogle Scholar
  29. 29.
    Heusch G (2015) Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning. Circ Res 116:674–699.  https://doi.org/10.1161/CIRCRESAHA.116.305348 CrossRefPubMedGoogle Scholar
  30. 30.
    Hsu JC, Laz T, Mohn KL, Taub R (1991) Identification of LRF-1, a leucine-zipper protein that is rapidly and highly induced in regenerating liver. Proc Natl Acad Sci USA 88:3511–3515CrossRefPubMedGoogle Scholar
  31. 31.
    Huang L, Zhang SM, Zhang P, Zhang XJ, Zhu LH, Chen K, Gao L, Zhang Y, Kong XJ, Tian S, Zhang XD, Li H (2014) Interferon regulatory factor 7 protects against vascular smooth muscle cell proliferation and neointima formation. J Am Heart Assoc 3:e001309.  https://doi.org/10.1161/JAHA.114.001309 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Inoue K, Zama T, Kamimoto T, Aoki R, Ikeda Y, Kimura H, Hagiwara M (2004) TNFalpha-induced ATF3 expression is bidirectionally regulated by the JNK and ERK pathways in vascular endothelial cells. Genes Cells 9:59–70 (707 [pii]) CrossRefPubMedGoogle Scholar
  33. 33.
    Jensen BC, Bultman SJ, Holley D, Tang W, de Ridder G, Pizzo S, Bowles D, Willis MS (2017) Upregulation of autophagy genes and the unfolded protein response in human heart failure. Int J Clin Exp Med 10:1051–1058PubMedPubMedCentralGoogle Scholar
  34. 34.
    Jiang DS, Liu Y, Zhou H, Zhang Y, Zhang XD, Zhang XF, Chen K, Gao L, Peng J, Gong H, Chen Y, Yang Q, Liu PP, Fan GC, Zou Y, Li H (2014) Interferon regulatory factor 7 functions as a novel negative regulator of pathological cardiac hypertrophy. Hypertension 63:713–722.  https://doi.org/10.1161/HYPERTENSIONAHA.113.02653 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Kalfon R, Koren L, Aviram S, Schwartz O, Hai T, Aronheim A (2017) ATF3 expression in cardiomyocytes preserves homeostasis in the heart and controls peripheral glucose tolerance. Cardiovasc Res 113:134–146.  https://doi.org/10.1093/cvr/cvw228 CrossRefPubMedGoogle Scholar
  36. 36.
    Kawauchi J, Zhang C, Nobori K, Hashimoto Y, Adachi MT, Noda A, Sunamori M, Kitajima S (2002) Transcriptional repressor activating transcription factor 3 protects human umbilical vein endothelial cells from tumor necrosis factor-alpha-induced apoptosis through down-regulation of p53 transcription. J Biol Chem 277:39025–39034.  https://doi.org/10.1074/jbc.M202974200 CrossRefPubMedGoogle Scholar
  37. 37.
    Kehat I, Molkentin JD (2010) Molecular pathways underlying cardiac remodeling during pathophysiological stimulation. Circulation 122:2727–2735.  https://doi.org/10.1161/CIRCULATIONAHA.110.942268 CrossRefPubMedGoogle Scholar
  38. 38.
    Kim JY, Park KJ, Hwang JY, Kim GH, Lee D, Lee YJ, Song EH, Yoo MG, Kim BJ, Suh YH, Roh GS, Gao B, Kim W, Kim WH (2017) Activating transcription factor 3 is a target molecule linking hepatic steatosis to impaired glucose homeostasis. J Hepatol 67:349–359.  https://doi.org/10.1016/j.jhep.2017.03.023 CrossRefPubMedGoogle Scholar
  39. 39.
    Koivisto E, Jurado Acosta A, Moilanen AM, Tokola H, Aro J, Pennanen H, Sakkinen H, Kaikkonen L, Ruskoaho H, Rysa J (2014) Characterization of the regulatory mechanisms of activating transcription factor 3 by hypertrophic stimuli in rat cardiomyocytes. PLoS One 9:e105168.  https://doi.org/10.1371/journal.pone.0105168 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Koren L, Alishekevitz D, Elhanani O, Nevelsky A, Hai T, Kehat I, Shaked Y, Aronheim A (2015) ATF3-dependent cross-talk between cardiomyocytes and macrophages promotes cardiac maladaptive remodeling. Int J Cardiol 198:232–240.  https://doi.org/10.1016/j.ijcard.2015.06.099 CrossRefPubMedGoogle Scholar
  41. 41.
    Koren L, Barash U, Zohar Y, Karin N, Aronheim A (2017) The cardiac maladaptive ATF3-dependent cross-talk between cardiomyocytes and macrophages is mediated by the IFNgamma-CXCL10-CXCR3 axis. Int J Cardiol 228:394–400.  https://doi.org/10.1016/j.ijcard.2016.11.159 CrossRefPubMedGoogle Scholar
  42. 42.
    Koren L, Elhanani O, Kehat I, Hai T, Aronheim A (2013) Adult cardiac expression of the activating transcription factor 3, ATF3, promotes ventricular hypertrophy. PLoS One 8:e68396.  https://doi.org/10.1371/journal.pone.0068396 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Kwak BR, Back M, Bochaton-Piallat ML, Caligiuri G, Daemen MJ, Davies PF, Hoefer IE, Holvoet P, Jo H, Krams R, Lehoux S, Monaco C, Steffens S, Virmani R, Weber C, Wentzel JJ, Evans PC (2014) Biomechanical factors in atherosclerosis: mechanisms and clinical implications. Eur Heart J 35(3013–3020):3020a–3020d.  https://doi.org/10.1093/eurheartj/ehu353 CrossRefGoogle Scholar
  44. 44.
    Lackland DT, Weber MA (2015) Global burden of cardiovascular disease and stroke: hypertension at the core. Can J Cardiol 31:569–571.  https://doi.org/10.1016/j.cjca.2015.01.009 CrossRefPubMedGoogle Scholar
  45. 45.
    Lavie CJ, Arena R, Alpert MA, Milani RV, Ventura HO (2017) Management of cardiovascular diseases in patients with obesity. Nat Rev Cardiol.  https://doi.org/10.1038/nrcardio.2017.108 PubMedCrossRefGoogle Scholar
  46. 46.
    Lazzeroni D, Rimoldi O, Camici PG (2016) From left ventricular hypertrophy to dysfunction and failure. Circ J 80:555–564.  https://doi.org/10.1253/circj.CJ-16-0062 CrossRefPubMedGoogle Scholar
  47. 47.
    Li Y, Li Z, Zhang C, Li P, Wu Y, Wang C, Bond Lau W, Ma XL, Du J (2017) Cardiac fibroblast-specific activating transcription factor 3 protects against heart failure by suppressing MAP2K3-p38 signaling. Circulation 135:2041–2057.  https://doi.org/10.1161/CIRCULATIONAHA.116.024599 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Liang G, Wolfgang CD, Chen BP, Chen TH, Hai T (1996) ATF3 gene. Genomic organization, promoter, and regulation. J Biol Chem 271:1695–1701CrossRefPubMedGoogle Scholar
  49. 49.
    Lin H, Li HF, Chen HH, Lai PF, Juan SH, Chen JJ, Cheng CF (2014) Activating transcription factor 3 protects against pressure-overload heart failure via the autophagy molecule Beclin-1 pathway. Mol Pharmacol 85:682–691.  https://doi.org/10.1124/mol.113.090092 CrossRefPubMedGoogle Scholar
  50. 50.
    Liu L, Liu J, Huang Z, Yu X, Zhang X, Dou D, Huang Y (2015) Berberine improves endothelial function by inhibiting endoplasmic reticulum stress in the carotid arteries of spontaneously hypertensive rats. Biochem Biophys Res Commun 458:796–801.  https://doi.org/10.1016/j.bbrc.2015.02.028 CrossRefPubMedGoogle Scholar
  51. 51.
    Lu D, Wolfgang CD, Hai T (2006) Activating transcription factor 3, a stress-inducible gene, suppresses Ras-stimulated tumorigenesis. J Biol Chem 281:10473–10481.  https://doi.org/10.1074/jbc.M509278200 CrossRefPubMedGoogle Scholar
  52. 52.
    Luo H, Wang J, Qiao C, Zhang X, Zhang W, Ma N (2015) ATF3 inhibits tenascin-C-induced foam cell formation in LPS-stimulated THP-1 macrophages by suppressing TLR-4. J Atheroscler Thromb 22:1214–1223.  https://doi.org/10.5551/jat.28415 CrossRefPubMedGoogle Scholar
  53. 53.
    Lusis AJ (2000) Atherosclerosis. Nature 407:233–241.  https://doi.org/10.1038/35025203 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Lv D, Meng D, Zou FF, Fan L, Zhang P, Yu Y, Fang J (2011) Activating transcription factor 3 regulates survivability and migration of vascular smooth muscle cells. IUBMB Life 63:62–69.  https://doi.org/10.1002/iub.416 CrossRefPubMedGoogle Scholar
  55. 55.
    Mancini GB, Cheng AY, Connelly K, Fitchett D, Goldenberg R, Goodman SG, Leiter LA, Lonn E, Paty B, Poirier P, Stone J, Thompson D, Yale JF (2017) Diabetes for cardiologists: practical issues in diagnosis and management. Can J Cardiol 33:366–377 (S0828-282X(16)30734-6) CrossRefPubMedGoogle Scholar
  56. 56.
    Masuda J, Usui R, Maru Y (2008) Fibronectin type I repeat is a nonactivating ligand for EphA1 and inhibits ATF3-dependent angiogenesis. J Biol Chem 283:13148–13155.  https://doi.org/10.1074/jbc.M702164200 CrossRefPubMedGoogle Scholar
  57. 57.
    Mo P, Wang H, Lu H, Boyd DD, Yan C (2010) MDM2 mediates ubiquitination and degradation of activating transcription factor 3. J Biol Chem 285:26908–26915.  https://doi.org/10.1074/jbc.M110.132597 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jimenez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB (2016) Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation 133:e38–e360.  https://doi.org/10.1161/CIR.0000000000000350 CrossRefPubMedGoogle Scholar
  59. 59.
    Nawa T, Nawa MT, Adachi MT, Uchimura I, Shimokawa R, Fujisawa K, Tanaka A, Numano F, Kitajima S (2002) Expression of transcriptional repressor ATF3/LRF1 in human atherosclerosis: colocalization and possible involvement in cell death of vascular endothelial cells. Atherosclerosis 161:281–291 (S0021-9150(01)00639-6) CrossRefPubMedGoogle Scholar
  60. 60.
    Nilsson M, Toftgard R, Bohm S (1995) Activated Ha-Ras but not TPA induces transcription through binding sites for activating transcription factor 3/Jun and a novel nuclear factor. J Biol Chem 270:12210–12218CrossRefPubMedGoogle Scholar
  61. 61.
    Nobori K, Ito H, Tamamori-Adachi M, Adachi S, Ono Y, Kawauchi J, Kitajima S, Marumo F, Isobe M (2002) ATF3 inhibits doxorubicin-induced apoptosis in cardiac myocytes: a novel cardioprotective role of ATF3. J Mol Cell Cardiol 34:1387–1397 (S0022282802920912) CrossRefPubMedGoogle Scholar
  62. 62.
    Nowak WN, Deng J, Ruan XZ, Xu Q (2017) Reactive oxygen species generation and atherosclerosis. Arterioscler Thromb Vasc Biol 37:e41–e52.  https://doi.org/10.1161/ATVBAHA.117.309228 CrossRefPubMedGoogle Scholar
  63. 63.
    Okamoto A, Iwamoto Y, Maru Y (2006) Oxidative stress-responsive transcription factor ATF3 potentially mediates diabetic angiopathy. Mol Cell Biol 26:1087–1097.  https://doi.org/10.1128/MCB.26.3.1087-1097.2006 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Okamoto Y, Chaves A, Chen J, Kelley R, Jones K, Weed HG, Gardner KL, Gangi L, Yamaguchi M, Klomkleaw W, Nakayama T, Hamlin RL, Carnes C, Altschuld R, Bauer J, Hai T (2001) Transgenic mice with cardiac-specific expression of activating transcription factor 3, a stress-inducible gene, have conduction abnormalities and contractile dysfunction. Am J Pathol 159:639–650.  https://doi.org/10.1016/S0002-9440(10)61735-X CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Poulter NR, Prabhakaran D, Caulfield M (2015) Hypertension. Lancet 386:801–812.  https://doi.org/10.1016/S0140-6736(14)61468-9 CrossRefPubMedGoogle Scholar
  66. 66.
    Retnakaran R, Zinman B (2008) Type 1 diabetes, hyperglycaemia, and the heart. Lancet 371:1790–1799.  https://doi.org/10.1016/S0140-6736(08)60767-9 CrossRefPubMedGoogle Scholar
  67. 67.
    Russo I, Frangogiannis NG (2016) Diabetes-associated cardiac fibrosis: cellular effectors, molecular mechanisms and therapeutic opportunities. J Mol Cell Cardiol 90:84–93.  https://doi.org/10.1016/j.yjmcc.2015.12.011 CrossRefPubMedGoogle Scholar
  68. 68.
    Sárközy M, Zvara A, Gyemant N, Fekete V, Kocsis GF, Pipis J, Szucs G, Csonka C, Puskas LG, Ferdinandy P, Csont T (2013) Metabolic syndrome influences cardiac gene expression pattern at the transcript level in male ZDF rats. Cardiovasc Diabetol 12:16.  https://doi.org/10.1186/1475-2840-12-16 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Seshasai SR, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N, Whincup PH, Mukamal KJ, Gillum RF, Holme I, Njolstad I, Fletcher A, Nilsson P, Lewington S, Collins R, Gudnason V, Thompson SG, Sattar N, Selvin E, Hu FB, Danesh J (2011) Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med 364:829–841.  https://doi.org/10.1056/NEJMoa1008862 CrossRefGoogle Scholar
  70. 70.
    Shah AM, Mann DL (2011) In search of new therapeutic targets and strategies for heart failure: recent advances in basic science. Lancet 378:704–712.  https://doi.org/10.1016/S0140-6736(11)60894-5 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Shimizu I, Minamino T (2016) Physiological and pathological cardiac hypertrophy. J Mol Cell Cardiol 97:245–262.  https://doi.org/10.1016/j.yjmcc.2016.06.001 CrossRefPubMedGoogle Scholar
  72. 72.
    Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321:405–412CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Teasdale JE, Hazell GG, Peachey AM, Sala-Newby GB, Hindmarch CC, McKay TR, Bond M, Newby AC, White SJ (2017) Cigarette smoke extract profoundly suppresses TNFalpha-mediated proinflammatory gene expression through upregulation of ATF3 in human coronary artery endothelial cells. Sci Rep 7:39945.  https://doi.org/10.1038/srep39945 CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Thompson MR, Xu D, Williams BR (2009) ATF3 transcription factor and its emerging roles in immunity and cancer. J Mol Med (Berl) 87:1053–1060.  https://doi.org/10.1007/s00109-009-0520-x CrossRefGoogle Scholar
  75. 75.
    Urmaliya V, Franchelli G (2017) A multidimensional sight on cardiac failure: uncovered from structural to molecular level. Heart Fail Rev 22:357–370.  https://doi.org/10.1007/s10741-017-9610-y CrossRefPubMedGoogle Scholar
  76. 76.
    van Albada ME, Bartelds B, Wijnberg H, Mohaupt S, Dickinson MG, Schoemaker RG, Kooi K, Gerbens F, Berger RM (2010) Gene expression profile in flow-associated pulmonary arterial hypertension with neointimal lesions. Am J Physiol Lung Cell Mol Physiol 298:L483–L491.  https://doi.org/10.1152/ajplung.00106.2009 CrossRefPubMedGoogle Scholar
  77. 77.
    Wang CM, Brennan VC, Gutierrez NM, Wang X, Wang L, Yang WH (2013) SUMOylation of ATF3 alters its transcriptional activity on regulation of TP53 gene. J Cell Biochem 114:589–598.  https://doi.org/10.1002/jcb.24396 CrossRefPubMedGoogle Scholar
  78. 78.
    Wang T, He R, Zhao J, Mei JC, Shao MZ, Pan Y, Zhang J, Wu HS, Yu M, Yan WC, Liu LM, Liu F, Jia WP (2017) Negative pressure wound therapy inhibits inflammation and upregulates activating transcription factor-3 and downregulates nuclear factor-kappaB in diabetic patients with foot ulcerations. Diabetes Metab Res Rev.  https://doi.org/10.1002/dmrr.2871 CrossRefPubMedGoogle Scholar
  79. 79.
    Yahiatene I, Aung HH, Wilson DW, Rutledge JC (2014) Single-molecule quantification of lipotoxic expression of activating transcription factor 3. Phys Chem Chem Phys 16:21595–21601.  https://doi.org/10.1039/c4cp03260h CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Yin T, Sandhu G, Wolfgang CD, Burrier A, Webb RL, Rigel DF, Hai T, Whelan J (1997) Tissue-specific pattern of stress kinase activation in ischemic/reperfused heart and kidney. J Biol Chem 272:19943–19950CrossRefPubMedGoogle Scholar
  81. 81.
    Yu M, Tsai SF, Kuo YM (2017) The therapeutic potential of anti-inflammatory exerkines in the treatment of atherosclerosis. Int J Mol Sci.  https://doi.org/10.3390/ijms18061260 CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Zhang T, Zhao LL, Cao X, Qi LC, Wei GQ, Liu JY, Yan SJ, Liu JG, Li XQ (2014) Bioinformatics analysis of time series gene expression in left ventricle (LV) with acute myocardial infarction (AMI). Gene 543:259–267.  https://doi.org/10.1016/j.gene.2014.04.002 CrossRefPubMedGoogle Scholar
  83. 83.
    Zhang WY, Franco DA, Schwartz E, D’Souza K, Karnick S, Reaven PD (2017) HDL inhibits saturated fatty acid mediated augmentation of innate immune responses in endothelial cells by a novel pathway. Atherosclerosis 259:83–96.  https://doi.org/10.1016/j.atherosclerosis.2016.09.003 CrossRefPubMedGoogle Scholar
  84. 84.
    Zhang ZB, Ruan CC, Chen DR, Zhang K, Yan C, Gao PJ (2016) Activating transcription factor 3 SUMOylation is involved in angiotensin II-induced endothelial cell inflammation and dysfunction. J Mol Cell Cardiol 92:149–157.  https://doi.org/10.1016/j.yjmcc.2016.02.001 CrossRefPubMedGoogle Scholar
  85. 85.
    Zhou H, Bian ZY, Zong J, Deng W, Yan L, Shen DF, Guo H, Dai J, Yuan Y, Zhang R, Lin YF, Hu X, Li H, Tang QZ (2012) Stem cell antigen 1 protects against cardiac hypertrophy and fibrosis after pressure overload. Hypertension 60:802–809.  https://doi.org/10.1161/HYPERTENSIONAHA.112.198895 CrossRefPubMedGoogle Scholar
  86. 86.
    Zhou H, Guo H, Zong J, Dai J, Yuan Y, Bian ZY, Tang QZ (2014) ATF3 regulates multiple targets and may play a dual role in cardiac hypertrophy and injury. Int J Cardiol 174:838–839.  https://doi.org/10.1016/j.ijcard.2014.04.160 CrossRefPubMedGoogle Scholar
  87. 87.
    Zhou H, Shen DF, Bian ZY, Zong J, Deng W, Zhang Y, Guo YY, Li H, Tang QZ (2011) Activating transcription factor 3 deficiency promotes cardiac hypertrophy, dysfunction, and fibrosis induced by pressure overload. PLoS One 6:e26744.  https://doi.org/10.1371/journal.pone.0026744 CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Zhou H, Yang HX, Yuan Y, Deng W, Zhang JY, Bian ZY, Zong J, Dai J, Tang QZ (2013) Paeoniflorin attenuates pressure overload-induced cardiac remodeling via inhibition of TGFbeta/Smads and NF-kappaB pathways. J Mol Histol 44:357–367.  https://doi.org/10.1007/s10735-013-9491-x CrossRefPubMedGoogle Scholar
  89. 89.
    Zhou H, Yuan Y, Ni J, Guo H, Deng W, Bian ZY, Tang QZ (2016) Pleiotropic and puzzling effects of ATF3 in maladaptive cardiac remodeling. Int J Cardiol 206:87–88.  https://doi.org/10.1016/j.ijcard.2016.01.143 CrossRefPubMedGoogle Scholar
  90. 90.
    Zhou Y, Zhao L, Zhang Z, Lu X (2015) Protective effect of enalapril against methionine-enriched diet-induced hypertension: role of endoplasmic reticulum and oxidative stress. Biomed Res Int 2015:724876.  https://doi.org/10.1155/2015/724876 PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of CardiologyRenmin Hospital of Wuhan UniversityWuhanPeople’s Republic of China
  2. 2.Cardiovascular Research InstituteWuhan UniversityWuhanPeople’s Republic of China
  3. 3.Hubei Key Laboratory of CardiologyWuhanPeople’s Republic of China
  4. 4.The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of HealthQilu Hospital of Shandong UniversityJinanPeople’s Republic of China

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