Journal of Molecular and Cellular Cardiology
Volume 47, Issue 2 , Pages 174-176 , August 2009

Cardiac fibroblasts on the fast track – Scleraxis: From Achilles' heel to anti-fibrotic therapy

  • Michal Kardasinski

      Affiliations

    • Research Group Cardiac Wounding and Healing, Interdisciplinary Center for Clinical Research (IZKF),
    • Department of Internal Medicine I, University Hospital, Julius-Maximilians-University, Würzburg, Germany
    • ,
  • Thomas Thum

      Affiliations

    • Research Group Cardiac Wounding and Healing, Interdisciplinary Center for Clinical Research (IZKF),
    • Department of Internal Medicine I, University Hospital, Julius-Maximilians-University, Würzburg, Germany
    • Corresponding Author InformationCorresponding author. Medizinische Klinik und Poliklinik I, Universitätsklinikum, Julius-Maximilians-Universität, Josef-Schneider-Str. 2, 97080 Würzburg, Germany.

Received 15 April 2009 ,Revised 13 May 2009 ,Accepted 13 May 2009.

References 

  1. Jessup M, Brozena S. Heart failure. N. Engl. J. Med. 2003;348:2007–2018
  2. Frantz S, Bauersachs J, Ertl G. Post-infarct remodelling: contribution of wound healing and inflammation. Cardiovasc. Res. 2009;81:474–481
  3. Jugdutt BI. Remodeling of the myocardium and potential targets in the collagen degradation and synthesis pathways. Curr. Drug Targets — Cardiovasc. Haematol. Disorders. 2003;3:1–30
  4. Bosman FT, Stamenkovic I. Functional structure and composition of the extracellular matrix. J. Pathol. 2003;200:423–428
  5. Kolditz DP, Wijffels MCEF, Blom NA, van der Laarse A, Hahurij ND, Lie-Venema , et al. Epicardium-derived cells in development of annulus fibrosis and persistence of accessory pathways. Circulation. 2008;117:1508–1517
  6. Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, et al. Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat. Med. 2007;13:952–961
  7. Eghbali M, Tomek R, Sukhatme VP, Woods C, Bhambi B. Differential effects of transforming growth factor-beta 1 and phorbol myristate acetate on cardiac fibroblasts. Regulation of fibrillar collagen mRNAs and expression of early transcription factors. Circ. Res. 1991;69:483–490
  8. Brown RD, Ambler SK, Mitchell MD, Long CS. The cardiac fibroblast: therapeutic target in myocardial remodeling and failure. Ann. Rev. Pharmacol. Toxicol. 2005;45:657–687
  9. van Amerongen MJ, Bou-Gharios G, Popa ER, Van Ark J, Petersen AH, Van Dam GM, et al. Bone marrow-derived myofibroblasts contribute functionally to scar formation after myocardial infarction. J. Pathol. 2008;214:377–386
  10. Bujak M, Frangogiannis NG. The role of TGF-{beta} signaling in myocardial infarction and cardiac remodeling. Cardiovasc. Res. 2007;74:184–195
  11. Wang B, Omar A, Angelovska T, Drobic V, Rattan SG, Jones SC, et al. Regulation of collagen synthesis by inhibitory Smad7 in cardiac myofibroblasts. Am. J. Physiol. Heart Circ. Physiol. 2007;293:H1282–H1290
  12. Hao J, Ju H, Zhao S, Junaid A, Scammell-La Fleur T, Dixon IMC. Elevation of expression of Smads 2, 3, and 4, decorin and TGF-[beta]in the chronic phase of myocardial infarct scar healing. J. Mol. Cell. Cardiol. 1999;31:667–678
  13. Bourajjaj M, Armand AS, da Costa Martins PA, Weijts B, van der Nagel R, Heeneman S, et al. NFATc2 is a necessary mediator of calcineurin-dependent cardiac hypertrophy and heart failure. J. Biol. Chem. 2008;283:22295–22303
  14. Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456:980–984
  15. Schultz JE, Witt SA, Nieman ML, Reiser PJ, Engle SJ, Zhou M, et al. Fibroblast growth factor-2 mediates pressure-induced hypertrophic response. J. Clin. Invest. 1999;104:709–719
  16. Espira L, Lamoureux L, Jones SC, Gerard RD, Dixon IMC, Czubryt MP. The basic helix–loop–helix transcription factor scleraxis regulates fibroblast collagen synthesis. J Mol Cell Cardiol. 2009;47:188–195
  17. Cserjesi P, Brown D, Ligon KL, Lyons GE, Copeland NG, Gilbert DJ, et al. Scleraxis: a basic helix–loop–helix protein that prefigures skeletal formation during mouse embryogenesis. Development. 1995;121:1099–1110
  18. Levay AK, Peacock JD, Lu Y, Koch M, Hinton RB, Kadler KE, et al. Scleraxis is required for cell lineage differentiation and extracellular matrix remodeling during murine heart valve formation in vivo. Circ. Res. 2008;103:948–956
  19. Breen E, Falco VM, Absher M, Cutroneo KR. Subpopulations of rat lung fibroblasts with different amounts of type I and type III collagen mRNAs. J. Biol. Chem. 1990;265:6286–6290
  20. Peng H, Carretero OA, Vuljaj N, Liao TD, Motivala A, Peterson EL, et al. Angiotensin-converting enzyme inhibitors: a new mechanism of action. Circulation. 2005;112:2436–2445
  21. Lijnen P, Petrov V. Induction of cardiac fibrosis by aldosterone. J. Mol. Cell. Cardiol. 2000;32:865–879
  22. Fraccarollo D, Galuppo P, Hildemann S, Christ M, Ertl G, Bauersachs J. Additive improvement of left ventricular remodeling and neurohormonal activation by aldosterone receptor blockade with eplerenone and ACE inhibition in rats with myocardial infarction. J. Am. Coll. Cardiol. 2003;42:1666–1673
  23. Dickstein K, Kjekshus J. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Lancet. 2002;360:752–760
  24. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N. Engl. J. Med. 2003;348:1309–1321
  25. Mirkovic S, Seymour AM, Fenning A, Strachan A, Margolin SB, et al. Attenuation of cardiac fibrosis by pirfenidone and amiloride in DOCA-salt hypertensive rats. Br. J. Pharmacol. 2002;135:961–968
  26. Kagitani S, Ueno H, Hirade S, Takahashi T, Takata M, et al. Tranilast attenuates myocardial fibrosis in association with suppression of monocyte/macrophage infiltration in DOCA/salthypertensive rats. J. Hypertens. 2004;22:1007–1015
  27. van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. PNAS. 2008;105:13027–13032
  28. Duisters RF, Tijsen AJ, Schroen B, Leenders JJ, Lentink V, van der Made I, et al miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ. Res. 2009;104:170–178
  29. Lejard V, Brideau G, Blais F, Salingcarnboriboon R, Wagner G, Roehrl MHA, et al. Scleraxis and NFATc regulate the expression of the pro-{alpha}1(I) collagen gene in tendon fibroblasts. J. Biol. Chem. 2007;282:17665–17675

PII: S0022-2828(09)00218-1

doi: 10.1016/j.yjmcc.2009.05.006

Journal of Molecular and Cellular Cardiology
Volume 47, Issue 2 , Pages 174-176 , August 2009

Article Tools

* Image Usage & Resolution