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Basic Research in Cardiology

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01.03.2011 | Original Contribution

Angiotensin II signaling up-regulates the immediate early transcription factor ATF3 in the left but not the right atrium

verfasst von: Tal Hasin, Ofer Elhanani, Zaid Abassi, Tsonwin Hai, Ami Aronheim

Erschienen in: Basic Research in Cardiology | Ausgabe 2/2011

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Abstract

The atria respond to various pathological stimuli including pressure and volume overload with remodeling and dilatation. Dilatation of the left atrium is associated with atrial fibrillation. The mechanisms involved in chamber-specific hypertrophy are largely unknown. Angiotensin II is hypothesized to take part in mediating this response. ATF3 is an immediate early gene found at the receiving end of multiple stress and growth stimuli. Here we characterize ATF3 as a direct target gene for angiotensin II. ATF3 expression is regulated by angiotensin receptor-mediated signaling in vivo and in vitro at the transcriptional level. ATF3 induction is mediated by cooperation between both the AT_1A and AT₂ receptor subtypes. While AT₂R blocker (PD123319) efficiently blocks ATF3 induction in response to angiotensin II injection, it results in an increase in blood pressure indicating that the effect of angiotensin II on ATF3 is independent of its effect on blood pressure. In contrast to adrenergic stimulation that induces ATF3 in all heart chambers, ATF3 induction in response to angiotensin II occurs primarily in the left chambers. We hypothesize that the activation of differential signaling pathways accounts for the chamber-specific induction of ATF3 expression in response to angiotensin II stimulation. Angiotensin II injection rapidly activates the EGFR-dependent pathways including ERK and PI3K-AKT in the left but not the right atrium. EGF receptor inhibitor (Gefitinib/Iressa) as well as the AKT inhibitor (Triciribine) significantly abrogates ATF3 induction by angiotensin II in the left chambers. Collectively, our data strongly place ATF3 as a unique nuclear protein target in response to angiotensin II stimulation in the atria. The spatial expression of ATF3 may add to the understanding of the signaling pathways involved in cardiac response to neuro-hormonal stimulation, and in particular to the understanding of left atrial-generated pathology such as atrial fibrillation.

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AbdAlla S, Lother H, Abdel-tawab AM, Quitterer U (2001) The angiotensin II AT2 receptor is an AT1 receptor antagonist. J Biol Chem 276:39721–39726. doi:10.1074/jbc.M105253200M105253200 PubMedCrossRef

Aronheim A, Zandi E, Hennemann H, Elledge S, Karin M (1997) Isolation of an AP-1 repressor by a novel method for detecting protein–protein interactions. Mol Cell Biol 17:3094–3102PubMed

Auger-Messier M, Turgeon ES, Leduc R, Escher E, Guillemette G (2005) The constitutively active N111G-AT1 receptor for angiotensin II modifies the morphology and cytoskeletal organization of HEK-293 cells. Exp Cell Res 308:188–195. doi:10.1016/j.yexcr.2005.04.015 PubMedCrossRef

Boldt A, Scholl A, Garbade J, Resetar ME, Mohr FW, Gummert JF, Dhein S (2006) ACE-inhibitor treatment attenuates atrial structural remodeling in patients with lone chronic atrial fibrillation. Basic Res Cardiol 101:261–267. doi:10.1007/s00395-005-0571-2 PubMedCrossRef

Braunwald E (1997) Shattuck lecture–cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med 337:1360–1369. doi:10.1056/NEJM199711063371906 PubMedCrossRef

Burstein B, Libby E, Calderone A, Nattel S (2008) Differential behaviors of atrial versus ventricular fibroblasts: a potential role for platelet-derived growth factor in atrial-ventricular remodeling differences. Circulation 117:1630–1641. doi:10.1161/CIRCULATIONAHA.107.748053 PubMedCrossRef

Casaclang-Verzosa G, Gersh BJ, Tsang TS (2008) Structural and functional remodeling of the left atrium: clinical and therapeutic implications for atrial fibrillation. J Am Coll Cardiol 51:1–11. doi:10.1016/j.jacc.2007.09.026 PubMedCrossRef

Chen BPC, Wolfgang CD, Hai T (1996) Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop. Mol Cell Biol 16:1157–1168PubMed

Cornelius T, Holmer SR, Muller FU, Riegger GA, Schunkert H (1997) Regulation of the rat atrial natriuretic peptide gene after acute imposition of left ventricular pressure overload. Hypertension 30:1348–1355PubMed

10.

D’Amore A, Black MJ, Thomas WG (2005) The angiotensin II type 2 receptor causes constitutive growth of cardiomyocytes and does not antagonize angiotensin II type 1 receptor-mediated hypertrophy. Hypertension 46:1347–1354. doi:10.1161/01.HYP.0000193504.51489.cf PubMedCrossRef

11.

Disertori M, Latini R, Barlera S, Franzosi MG, Staszewsky L, Maggioni AP, Lucci D, Di Pasquale G, Tognoni G (2009) Valsartan for prevention of recurrent atrial fibrillation. N Eng J Med 360:1606–1617. doi:10.1056/NEJMoa0805710 CrossRef

12.

Fentzke RC, Korcarz CE, Lang RM, Lin H, Leiden JM (1998) Dilated cardiomyopathy in transgenic mice expressing a dominant-negative CREB transcription factor in the heart. J Clin Invest 101:2415–2426. doi:10.1172/JCI2950 PubMedCrossRef

13.

Frey N, Olson EN (2003) Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol 65:45–79PubMedCrossRef

14.

Gao MH, Tang T, Guo T, Sun SQ, Feramisco JR, Hammond HK (2004) Adenylyl cyclase type VI gene transfer reduces phospholamban expression in cardiac myocytes via activating transcription factor 3. J Biol Chem 279:38797–38802. doi:10.1074/jbc.M405701200M405701200 PubMedCrossRef

15.

Gillis AM (2009) Angiotensin-receptor blockers for prevention of atrial fibrillation—a matter of timing or target? N Engl J Med 360:1669–1671. doi:10.1056/NEJMe0901602 PubMedCrossRef

16.

Hai T (2006) The ATF transcription factors in cellular adaptive responses. In: Ma J (ed) Gene expression and regulation. Higher Education Press, Beijing; Springer, New York, pp 329–340

17.

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 273:1–11PubMedCrossRef

18.

Hai T, Wolfgang CD, Marsee DK, Allen AE, Sivaprasad U (1999) ATF3 and stress responses. Gene Express 7:321–335

19.

Hein L, Barsh GS, Pratt RE, Dzau VJ, Kobilka BK (1995) Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice. Nature 377:744–747. doi:10.1038/377744a0 PubMedCrossRef

20.

Hein L, Stevens ME, Barsh GS, Pratt RE, Kobilka BK, Dzau VJ (1997) Overexpression of angiotensin AT1 receptor transgene in the mouse myocardium produces a lethal phenotype associated with myocyte hyperplasia and heart block. Proc Natl Acad Sci USA 94:6391–6396PubMedCrossRef

21.

Hilfiker-Kleiner D, Hilfiker A, Kaminski K, Schaefer A, Park JK, Michel K, Quint A, Yaniv M, Weitzman JB, Drexler H (2005) Lack of JunD promotes pressure overload-induced apoptosis, hypertrophic growth, and angiogenesis in the heart. Circulation 112:1470–1477. doi:10.1161/CIRCULATIONAHA.104.518472 PubMedCrossRef

22.

Ichihara S, Senbonmatsu T, Price E Jr, Ichiki T, Gaffney FA, Inagami T (2001) Angiotensin II type 2 receptor is essential for left ventricular hypertrophy and cardiac fibrosis in chronic angiotensin II-induced hypertension. Circulation 104:346–351PubMed

23.

Ichiki T, Labosky PA, Shiota C, Okuyama S, Imagawa Y, Fogo A, Niimura F, Ichikawa I, Hogan BL, Inagami T (1995) Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. Nature 377:748–750. doi:10.1038/377748a0 PubMedCrossRef

24.

Jin C, Ugai H, Song J, Murata T, Nili F, Sun K, Horikoshi M, Yokoyama KK (2001) Identification of mouse Jun dimerization protein 2 as a novel repressor of ATF-2. FEBS Lett 489:34–41PubMedCrossRef

25.

Kehat I, Hasin T, Aronheim A (2006) The role of basic leucine zipper protein-mediated transcription in physiological and pathological myocardial hypertrophy. Ann N Y Acad Sci 1080:97–109. doi:10.1196/annals.1380.009 PubMedCrossRef

26.

Kehat I, Heinrich R, Ben-Izhak O, Miyazaki H, Gutkind JS, Aronheim A (2006) Inhibition of basic leucine zipper transcription is a major mediator of atrial dilatation. Cardiovasc Res 70:543–554. doi:10.1016/j.cardiores.2006.02.018 PubMedCrossRef

27.

Kovacic-Milivojevic B, Gardner DG (1995) Fra-1, a Fos gene family member that activates atrial natriuretic peptide gene transcription. Hypertension 25:679–682PubMed

28.

Li Y, Li WM, Gong YT, Li BX, Liu W, Han W, Dong D, Sheng L, Xue JY, Zhang L, Chu S, Yang BF (2007) The effects of cilazapril and valsartan on the mRNA and protein expressions of atrial calpains and atrial structural remodeling in atrial fibrillation dogs. Basic Res Cardiol 102:245–256. doi:10.1007/s00395-007-0641-8 PubMedCrossRef

29.

Mehta PK, Griendling KK (2007) Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol 292:C82–C97. doi:10.1152/ajpcell.00287.2006 CrossRef

30.

Molkentin JD, Dorn GW 2nd (2001) Cytoplasmic signaling pathways that regulate cardiac hypertrophy. Annu Rev Physiol 63:391–426. doi:10.1146/annurev.physiol.63.1.39163/1/391 PubMedCrossRef

31.

Nadruz W Jr, Kobarg CB, Kobarg J, Franchini KG (2004) c-Jun is regulated by combination of enhanced expression and phosphorylation in acute-overloaded rat heart. Am J Physiol Heart Circ Physiol 286:H760–H767. doi:10.1152/ajpheart.00430.200300430.2003 PubMedCrossRef

32.

Nakajima M, Hutchinson HG, Fujinaga M, Hayashida W, Morishita R, Zhang L, Horiuchi M, Pratt RE, Dzau VJ (1995) The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: gain-of-function study using gene transfer. Proc Natl Acad Sci USA 92:10663–10667PubMedCrossRef

33.

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 159:639–650PubMedCrossRef

34.

Rakesh K, Yoo B, Kim IM, Salazar N, Kim KS, Rockman HA (2010) Beta-Arrestin-biased agonism of the angiotensin receptor induced by mechanical stress. Sci Signal 3:ra46 doi: 3/125/ra46 [pii] 10.1126/scisignal.2000769

35.

Reudelhuber TL (2005) The continuing saga of the AT2 receptor: a case of the good, the bad, and the innocuous. Hypertension 46:1261–1262. doi:10.1161/01.HYP.0000193498.07087.83 PubMedCrossRef

36.

Rockman HA, Ross RS, Harris AN, Knowlton KU, Steinhelper ME, Field LJ, Ross J Jr, Chien KR (1991) Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy. Proc Natl Acad Sci USA 88:8277–8281PubMedCrossRef

37.

Saygili E, Rana OR, Meyer C, Gemein C, Andrzejewski MG, Ludwig A, Weber C, Schotten U, Kruttgen A, Weis J, Schwinger RH, Mischke K, Rassaf T, Kelm M, Schauerte P (2009) The angiotensin-calcineurin-NFAT pathway mediates stretch-induced up-regulation of matrix metalloproteinases-2/-9 in atrial myocytes. Basic Res Cardiol 104:435–448. doi:10.1007/s00395-008-0772-6 PubMedCrossRef

38.

Scow DT, Smith EG, Shaughnessy AF (2003) Combination therapy with ACE inhibitors and angiotensin-receptor blockers in heart failure. Am Fam Phys 68:1795–1798

39.

Shah BH, Catt KJ (2003) A central role of EGF receptor transactivation in angiotensin II-induced cardiac hypertrophy. Trends Pharmacol Sci 24:239–244PubMed

40.

Shaulian E, Karin M (2002) AP-1 as a regulator of cell life and death. N Cell Biol 4:E131–E136. doi:10.1038/ncb0502-e131ncb0502-e131 CrossRef

41.

Smith NJ, Chan HW, Osborne JE, Thomas WG, Hannan RD (2004) Hijacking epidermal growth factor receptors by angiotensin II: new possibilities for understanding and treating cardiac hypertrophy. Cell Mol Life Sci 61:2695–2703. doi:10.1007/s00018-004-4244-3 PubMedCrossRef

42.

Stoll M, Steckelings UM, Paul M, Bottari SP, Metzger R, Unger T (1995) The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. J Clin Invest 95:651–657. doi:10.1172/JCI117710 PubMedCrossRef

43.

Tabibiazar R, Wagner RA, Liao A, Quertermous T (2003) Transcriptional profiling of the heart reveals chamber-specific gene expression patterns. Circ Res 93:1193–1201. doi:10.1161/01.RES.0000103171.42654.DD01.RES.0000103171.42654.DD PubMedCrossRef

44.

Timmermans PB, Wong PC, Chiu AT, Herblin WF, Benfield P, Carini DJ, Lee RJ, Wexler RR, Saye JA, Smith RD (1993) Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev 45:205–251PubMed

45.

Wachtell K, Lehto M, Gerdts E, Olsen MH, Hornestam B, Dahlof B, Ibsen H, Julius S, Kjeldsen SE, Lindholm LH, Nieminen MS, Devereux RB (2005) Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol: the losartan intervention for end point reduction in hypertension (LIFE) study. J Am Coll Cardiol 45:712–719. doi:10.1016/j.jacc.2004.10.068 PubMedCrossRef

46.

Wattigney WA, Mensah GA, Croft JB (2003) Increasing trends in hospitalization for atrial fibrillation in the United States, 1985 through 1999: implications for primary prevention. Circulation 108:711–716. doi:10.1161/01.CIR.0000083722.42033.0A01.CIR.0000083722.42033.0A PubMedCrossRef

47.

Wharton J, Morgan K, Rutherford RA, Catravas JD, Chester A, Whitehead BF, De Leval MR, Yacoub MH, Polak JM (1998) Differential distribution of angiotensin AT2 receptors in the normal and failing human heart. J Pharmacol Exp Ther 284:323–336PubMed

48.

Xiao HD, Fuchs S, Campbell DJ, Lewis W, Dudley SC Jr, Kasi VS, Hoit BD, Keshelava G, Zhao H, Capecchi MR, Bernstein KE (2004) Mice with cardiac-restricted angiotensin-converting enzyme (ACE) have atrial enlargement, cardiac arrhythmia, and sudden death. Am J Pathol 165:1019–1032PubMedCrossRef

49.

Zou Y, Akazawa H, Qin Y, Sano M, Takano H, Minamino T, Makita N, Iwanaga K, Zhu W, Kudoh S, Toko H, Tamura K, Kihara M, Nagai T, Fukamizu A, Umemura S, Iiri T, Fujita T, Komuro I (2004) Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II. N cell Biol 6:499–506. doi:10.1038/ncb1137ncb1137 CrossRef

Titel: Angiotensin II signaling up-regulates the immediate early transcription factor ATF3 in the left but not the right atrium
verfasst von: Tal Hasin
Ofer Elhanani
Zaid Abassi
Tsonwin Hai
Ami Aronheim
Publikationsdatum: 01.03.2011
Verlag: Springer-Verlag
Erschienen in: Basic Research in Cardiology / Ausgabe 2/2011
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-010-0145-9

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