Heart Rhythm
Volume 6, Issue 6 , Pages 848-856 , June 2009

Myofibroblasts in diseased hearts: New players in cardiac arrhythmias?

  • Stephan Rohr, MD

      Affiliations

    • Corresponding Author InformationAddress reprint requests and correspondence: Dr. Stephan Rohr, Department of Physiology, University of Bern, Buehlplatz 5, CH-3012 Bern, Switzerland

Received 12 February 2009 ,Accepted 22 February 2009.

References 

  1. Maisch B. Extracellular matrix and cardiac interstitium: restriction is not a restricted phenomenon. Herz. 1995;20:75–80
  2. McAnulty RJ, Laurent GJ. Collagen synthesis and degradation in vivo (Evidence for rapid rates of collagen turnover with extensive degradation of newly synthesized collagen in tissues of the adult rat). Coll Relat Res. 1987;7:93–104
  3. Swynghedauw B. Molecular mechanisms of myocardial remodeling. Physiol Rev. 1999;79:215–262
  4. Adamson PB, Barr RC, Callans DJ, et al. The perplexing complexity of cardiac arrhythmias: beyond electrical remodeling. Heart Rhythm. 2005;2:650–659
  5. Spach MS, Boineau JP. Microfibrosis produces electrical load variations due to loss of side-to-side cell connections: a major mechanism of structural heart disease arrhythmias. Pacing Clin Electrophysiol. 1997;20:397–413
  6. De Bakker JMT, Van Capelle FJL, Janse MJ, et al. Slow conduction in the infarcted human heart: zigzag course of activation. Circulation. 1993;88:915–926
  7. Weber KT. Extracellular matrix remodeling in heart failure: a role for de novo angiotensin II generation. Circulation. 1997;96:4065–4082
  8. Weber KT. Fibrosis in hypertensive heart disease: focus on cardiac fibroblasts. J Hypertension. 2004;22:47–50
  9. Gabbiani G. The myofibroblast in wound healing and fibrocontractive diseases. J Pathol. 2003;200:500–503
  10. Kisseleva T, Brenner DA. Fibrogenesis of parenchymal organs. Proc Am Thorac Soc. 2008;5:338–342
  11. Aikawa E, Whittaker P, Farber M, et al. Human semilunar cardiac valve remodeling by activated cells from fetus to adult: implications for postnatal adaptation, pathology, and tissue engineering. Circulation. 2006;113:1344–1352
  12. Leslie KO, Taatjes DJ, Schwarz J, et al. Cardiac myofibroblasts express alpha smooth muscle actin during right ventricular pressure overload in the rabbit. Am J Pathol. 1991;139:207–216
  13. Kuwahara F, Kai H, Tokuda K, et al. Transforming growth factor function blocking prevents myocardial fibrosis and diastolic dysfunction in pressure-overloaded rats. Circ. 2002;106:130–135
  14. Peterson DJ, Ju H, Panagia M, et al. Expression of Gi-2α and Gsα in myofibroblasts localized to the infarct scar in heart failure due to myocardial infarction. Cardiovasc Res. 1999;41:575–585
  15. Willems IE, Havenith MG, De Mey JG, et al. The alpha-smooth muscle actin-positive cells in healing human myocardial scars. Am J Pathol. 1994;145:868–875
  16. Sun Y, Kiani MF, Postlethwaite AE, et al. Infarct scar as living tissue. Basic Res Cardiol. 2002;97:343–347
  17. Desmouliere A, Chapponier C, Gabbiani G. Tissue repair, contraction, and the myofibroblast. Wound Rep Reg. 2005;13:7–12
  18. van Amerongen M, Bou-Gharios G, Popa E, et al. Bone marrow-derived myofibroblasts contribute functionally to scar formation after myocardial infarction. J Pathol. 2008;214:377–386
  19. Weber KT. From inflammation to fibrosis: a stiff stretch of highway. Hypertension. 2004;43:716–719
  20. Kuwahara F, Kai H, Tokuda K, et al. Hypertensive myocardial fibrosis and diastolic dysfunction. Hypertension. 2004;43:739–745
  21. Manabe I, Shindo T, Nagai R. Gene expression in fibroblasts and fibrosis. Circ Res. 2002;91:1103–1113
  22. Sui GP, Rothery S, Dupont E, et al. Gap junctions and connexin expression in human suburothelial interstitial cells. BJU Int. 2002;90:118–129
  23. Powell DW, Mifflin RC, Valentich JD, et al. Myofibroblasts (II. Intestinal subepithelial myofibroblasts). Am J Physiol. 1999;277:C183–C201
  24. Jamieson S, Going JJ, D'Arcy R, et al. Expression of gap junction proteins connexin 26 and connexin 43 in normal human breast and in breast tumours. J Pathol. 1998;184:37–43
  25. Gabbiani G, Chaponnier C, Huttner I. Cytoplasmic filaments and gap junctions in epithelial cells and myofibroblasts during wound healing. J Cell Biol. 1978;76:561–568
  26. Camelliti P, Devlin GP, Matthews KG, et al. Spatially and temporally distinct expression of fibroblast connexins after sheep ventricular infarction. Cardiovasc Res. 2004;62:415
  27. Sun Y, Weber KT. Angiotensin converting enzyme and myofibroblasts during tissue repair in the rat heart. J Mol Cell Cardiol. 1996;28:851–858
  28. Hyde AB, Blondel B, Matter A, et al. Homo- and heterocellular junctions in cell cultures: an electrophysiological and morphological study. Prog Brain Res. 1969;31:283–311
  29. Miragoli M, Gaudesius G, Rohr S. Electrotonic modulation of cardiac impulse conduction by myofibroblasts. Circ Res. 2006;98:801–810
  30. Lefroy DC, Fang JC, Stevenson LW, et al. Recipient-to-donor atrioatrial conduction after orthotopic heart transplantation: surface electrocardiographic features and estimated prevalence. Am J Cardiol. 1998;82:444–450
  31. Gaudesius G, Miragoli M, Thomas SP, et al. Coupling of cardiac electrical activity over extended distances by fibroblasts of cardiac origin. Circ Res. 2003;93:421–428
  32. Rohr S, Flückiger-Labrada R, Kucera JP. Photolithographically defined deposition of attachment factors as a versatile method for patterning the growth of different cell types in culture. Eur J Physiol. 2003;446:125–132
  33. Rohr S, Kucera JP. Optical recording system based on a fiber optic image conduit: assessment of microscopic activation patterns in cardiac tissue. Biophys J. 1998;75:1062–1075
  34. Peters NS, Wit AL. Myocardial architecture and ventricular arrhythmogenesis. Circulation. 1998;97:1746–1754
  35. De Bakker JMT, Stein M, van Rijen HVM. Three-dimensional anatomic structure as substrate for ventricular tachycardia/ventricular fibrillation. Heart Rhythm. 2005;2:777–779
  36. Wilders R, Wagner MB, Golod GA, et al. Effects of anisotropy on the development of cardiac arrhythmias associated with focal activity. Eur J Physiol. 2000;441:301–312
  37. Mohabir R, Ferrier GR. Effects of ischemic conditions and reperfusion on depolarization-induced automaticity. Am J Physiol. 1988;255:H992–H999
  38. Miragoli M, Salvarani N, Rohr S. Myofibroblasts induce ectopic activity in cardiac tissue. Circ Res. 2007;101:755–758
  39. Zlochiver S, MuÒoz V, Vikstrom KL, et al. Electrotonic myofibroblast-to-myocyte coupling increases propensity to reentrant arrhythmias in two-dimensional cardiac monolayers. Biophys J. 2008;95:4469–4480
  40. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo (The cardiac arrhythmia suppression trial). N Engl J Med. 1991;324:781–788
  41. Heubach JF, Graf EM, Leutheuser J, et al. Electrophysiological properties of human mesenchymal stem cells. J Physiol. 2004;554:659–672

 This work was supported by the Swiss National Science Foundation (Grant 320000-118247/1).

PII: S1547-5271(09)00230-6

doi: 10.1016/j.hrthm.2009.02.038

Heart Rhythm
Volume 6, Issue 6 , Pages 848-856 , June 2009