Circulation Research. 2004;94:1458-1465
Published online before print April 29, 2004, doi: 10.1161/01.RES.0000129579.59664.9d
Published online before print April 29, 2004, doi: 10.1161/01.RES.0000129579.59664.9d
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2004 American Heart Association, Inc.
Integrative Physiology |
Increased Vulnerability to Atrial Fibrillation in Transgenic Mice With Selective Atrial Fibrosis Caused by Overexpression of TGF-ß1
From Krannert Institute of Cardiology (S.V., S.K.E., D.O.), Indiana University School of Medicine, Indianapolis, Ind; Cardiac Electrophysiology (T.S., T.E., J.E.O.), Division of Cardiology and the Cardiovascular Research Institute, University of California San Francisco, San Francisco, Calif; Herman B. Wells Center for Pediatric Research (M.R.-v.d.L., H.O.N., H.N., L.J.F.), Indiana University School of Medicine, Indianapolis, Ind.
Correspondence to Jeffrey E. Olgin, University of California San Francisco, 500 Parnasus Ave, MU East 4/Box 1354, San Francisco, CA 94143-1354. E-mail olgin{at}medicine.ucsf.edu
Studies on patients and large animal models suggest the importance of atrial fibrosis in the development of atrial fibrillation (AF). To investigate whether increased fibrosis is sufficient to produce a substrate for AF, we have studied cardiac electrophysiology (EP) and inducibility of atrial arrhythmias in MHC-TGFcys33ser transgenic mice (Tx), which have increased fibrosis in the atrium but not in the ventricles. In anesthetized mice, wild-type (Wt) and Tx did not show significant differences in surface ECG parameters. With transesophageal atrial pacing, no significant differences were observed in EP parameters, except for a significant decrease in corrected sinus node recovery time in Tx mice. Burst pacing induced AF in 14 of 29 Tx mice, whereas AF was not induced in Wt littermates (P<0.01). In Langendorff perfused hearts, atrial conduction was studied using a 16-electrode array. Epicardial conduction velocity was significantly decreased in the Tx RA compared with the Wt RA. In the Tx LA, conduction velocity was not significantly different from Wt, but conduction was more heterogeneous. Action potential characteristics recorded with intracellular microelectrodes did not reveal differences between Wt and Tx mice in either atrium. Thus, in this transgenic mouse model, selective atrial fibrosis is sufficient to increase AF inducibility.
Key Words: atrial fibrillation • fibrosis • growth factors
This article has been cited by other articles:
 |
|
 |
|
  K. Nishida, G. Michael, D. Dobrev, and S. Nattel Animal models for atrial fibrillation: clinical insights and scientific opportunities Europace, October 29, 2009; (2009) eup328v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Rennison and D. R. Van Wagoner Impact of Dietary Fatty Acids on Cardiac Arrhythmogenesis Circ Arrhythm Electrophysiol, August 1, 2009; 2(4): 460 - 469. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xie, A. Garfinkel, J. N. Weiss, and Z. Qu Cardiac alternans induced by fibroblast-myocyte coupling: mechanistic insights from computational models Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H775 - H784. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Shan, Y. Zhang, Y. Lu, Y. Zhang, Z. Pan, B. Cai, N. Wang, X. Li, T. Feng, Y. Hong, et al. Downregulation of miR-133 and miR-590 contributes to nicotine-induced atrial remodelling in canines Cardiovasc Res, August 1, 2009; 83(3): 465 - 472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kirchhof, J. Bax, C. Blomstrom-Lundquist, H. Calkins, A. J. Camm, R. Cappato, F. Cosio, H. Crijns, H.-C. Diener, A. Goette, et al. Early and comprehensive management of atrial fibrillation: Proceedings from the 2nd AFNET/EHRA consensus conference on atrial fibrillation entitled 'research perspectives in atrial fibrillation' Europace, July 1, 2009; 11(7): 860 - 885. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Kirchhof, J. Bax, C. Blomstrom-Lundquist, H. Calkins, A. John Camm, R. Cappato, F. Cosio, H. Crijns, H.-C. Diener, A. Goette, et al. Early and comprehensive management of atrial fibrillation: executive summary of the proceedings from the 2nd AFNET-EHRA consensus conference 'research perspectives in AF' Eur. Heart J., June 17, 2009; (2009) ehp235v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. K. On, E.-S. Jeon, S. Y. Lee, D.-H. Shin, J.-O. Choi, J. Sung, J. S. Kim, K. Sung, and P. Park Plasma transforming growth factor beta1 as a biochemical marker to predict the persistence of atrial fibrillation after the surgical maze procedure. J. Thorac. Cardiovasc. Surg., June 1, 2009; 137(6): 1515 - 1520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Oakes, T. J. Badger, E. G. Kholmovski, N. Akoum, N. S. Burgon, E. N. Fish, J. J.E. Blauer, S. N. Rao, E. V.R. DiBella, N. M. Segerson, et al. Detection and Quantification of Left Atrial Structural Remodeling With Delayed-Enhancement Magnetic Resonance Imaging in Patients With Atrial Fibrillation Circulation, April 7, 2009; 119(13): 1758 - 1767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R Balasubramaniam and P M Kistler Atrial fibrillation in heart failure: the chicken or the egg? Heart, April 1, 2009; 95(7): 535 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S R Lalani, J V Thakuria, G F Cox, X Wang, W Bi, M S Bray, C Shaw, S W Cheung, A C Chinault, B A Boggs, et al. 20p12.3 microdeletion predisposes to Wolff-Parkinson-White syndrome with variable neurocognitive deficits J. Med. Genet., March 1, 2009; 46(3): 168 - 175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Benjamin, P.-S. Chen, D. E. Bild, A. M. Mascette, C. M. Albert, A. Alonso, H. Calkins, S. J. Connolly, A. B. Curtis, D. Darbar, et al. Prevention of Atrial Fibrillation: Report From a National Heart, Lung, and Blood Institute Workshop Circulation, February 3, 2009; 119(4): 606 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Camm, P. Kirchhof, G. Y.H. Lip, I. Savelieva, and S. Ernst CHAPTER 29 Atrial Fibrillation ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. von Lewinski, J. Kockskamper, S.-U. Rubertus, D. Zhu, J. D. Schmitto, F. A. Schondube, G. Hasenfuss, and B. Pieske Direct pro-arrhythmogenic effects of angiotensin II can be suppressed by AT1 receptor blockade in human atrial myocardium Eur J Heart Fail, December 1, 2008; 10(12): 1172 - 1176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Etzion, M. Mor, A. Shalev, S. Dror, O. Etzion, A. Dagan, O. Beharier, A. Moran, and A. Katz New insights into the atrial electrophysiology of rodents using a novel modality: the miniature-bipolar hook electrode Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1460 - H1469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Serra and M. Bendersky Review: Atrial fibrillation and renin-angiotensin system Therapeutic Advances in Cardiovascular Disease, June 1, 2008; 2(3): 215 - 223. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Ogata, T. Ueyama, K. Isodono, M. Tagawa, N. Takehara, T. Kawashima, K. Harada, T. Takahashi, T. Shioi, H. Matsubara, et al. MURC, a Muscle-Restricted Coiled-Coil Protein That Modulates the Rho/ROCK Pathway, Induces Cardiac Dysfunction and Conduction Disturbance Mol. Cell. Biol., May 15, 2008; 28(10): 3424 - 3436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nattel, B. Burstein, and D. Dobrev Atrial Remodeling and Atrial Fibrillation: Mechanisms and Implications Circ Arrhythm Electrophysiol, April 1, 2008; 1(1): 62 - 73. [Full Text] [PDF]
|
|
|
|
|
|
B. Burstein, E. Libby, A. Calderone, and S. Nattel Differential Behaviors of Atrial Versus Ventricular Fibroblasts: A Potential Role for Platelet-Derived Growth Factor in Atrial-Ventricular Remodeling Differences Circulation, April 1, 2008; 117(13): 1630 - 1641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Burstein and S. Nattel Atrial Fibrosis: Mechanisms and Clinical Relevance in Atrial Fibrillation J. Am. Coll. Cardiol., February 26, 2008; 51(8): 802 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-T. Tsai, L.-P. Lai, K.-T. Kuo, J.-J. Hwang, C.-S. Hsieh, K.-L. Hsu, C.-D. Tseng, Y.-Z. Tseng, F.-T. Chiang, and J.-L. Lin Angiotensin II Activates Signal Transducer and Activators of Transcription 3 via Rac1 in Atrial Myocytes and Fibroblasts: Implication for the Therapeutic Effect of Statin in Atrial Structural Remodeling Circulation, January 22, 2008; 117(3): 344 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Sampson, C. Terrenoire, D. O. Cervantes, R. A. Kaba, N. S. Peters, and R. S. Kass Adrenergic regulation of a key cardiac potassium channel can contribute to atrial fibrillation: evidence from an IKs transgenic mouse J. Physiol., January 15, 2008; 586(2): 627 - 637. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Tanaka, S. Zlochiver, Karen. L. Vikstrom, M. Yamazaki, J. Moreno, M. Klos, Alexey. V. Zaitsev, R. Vaidyanathan, D. S. Auerbach, S. Landas, et al. Spatial Distribution of Fibrosis Governs Fibrillation Wave Dynamics in the Posterior Left Atrium During Heart Failure Circ. Res., October 12, 2007; 101(8): 839 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. E. Bondarenko and R. L. Rasmusson Simulations of propagated mouse ventricular action potentials: effects of molecular heterogeneity Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1816 - H1832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Fischer, R. Dechend, A. Gapelyuk, E. Shagdarsuren, K. Gruner, A. Gruner, P. Gratze, F. Qadri, M. Wellner, A. Fiebeler, et al. Angiotensin II-induced sudden arrhythmic death and electrical remodeling Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H1242 - H1253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Adam, G. Frost, F. Custodis, M. A. Sussman, H.-J. Schafers, M. Bohm, and U. Laufs Role of Rac1 GTPase Activation in Atrial Fibrillation J. Am. Coll. Cardiol., July 24, 2007; 50(4): 359 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jahangir, V. Lee, P. A. Friedman, J. M. Trusty, D. O. Hodge, S. L. Kopecky, D. L. Packer, S. C. Hammill, W.-K. Shen, and B. J. Gersh Long-Term Progression and Outcomes With Aging in Patients With Lone Atrial Fibrillation: A 30-Year Follow-Up Study Circulation, June 19, 2007; 115(24): 3050 - 3056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-K. Park, R. Fischer, R. Dechend, E. Shagdarsuren, A. Gapeljuk, M. Wellner, S. Meiners, P. Gratze, N. Al-Saadi, S. Feldt, et al. p38 Mitogen-Activated Protein Kinase Inhibition Ameliorates Angiotensin II-Induced Target Organ Damage Hypertension, March 1, 2007; 49(3): 481 - 489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C.M. Choisy, L. A. Arberry, J. C. Hancox, and A. F. James Increased Susceptibility to Atrial Tachyarrhythmia in Spontaneously Hypertensive Rat Hearts Hypertension, March 1, 2007; 49(3): 498 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cardin, E. Libby, P. Pelletier, S. Le Bouter, A. Shiroshita-Takeshita, N. Le Meur, J. Leger, S. Demolombe, A. Ponton, L. Glass, et al. Contrasting Gene Expression Profiles in Two Canine Models of Atrial Fibrillation Circ. Res., February 16, 2007; 100(3): 425 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ono, H. Hayashi, A. Kawase, S.-F. Lin, H. Li, J. N. Weiss, P.-S. Chen, and H. S. Karagueuzian Spontaneous atrial fibrillation initiated by triggered activity near the pulmonary veins in aged rats subjected to glycolytic inhibition Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H639 - H648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Avila, I. M. Medina, E. Jimenez, G. Elizondo, and C. I. Aguilar Transforming growth factor-beta1 decreases cardiac muscle L-type Ca2+ current and charge movement by acting on the Cav1.2 mRNA Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H622 - H631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. H. Everett IV, E. E. Wilson, S. Verheule, J. M. Guerra, S. Foreman, and J. E. Olgin Structural atrial remodeling alters the substrate and spatiotemporal organization of atrial fibrillation: a comparison in canine models of structural and electrical atrial remodeling Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2911 - H2923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Lee, T. H. Everett IV, D. Rahmutula, J. M. Guerra, E. Wilson, C. Ding, and J. E. Olgin Pirfenidone Prevents the Development of a Vulnerable Substrate for Atrial Fibrillation in a Canine Model of Heart Failure Circulation, October 17, 2006; 114(16): 1703 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Ehrlich, S. H. Hohnloser, and S. Nattel Role of angiotensin system and effects of its inhibition in atrial fibrillation: clinical and experimental evidence Eur. Heart J., March 1, 2006; 27(5): 512 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Saba, A. M. Janczewski, L. C. Baker, V. Shusterman, E. C. Gursoy, A. M. Feldman, G. Salama, C. F. McTiernan, and B. London Atrial contractile dysfunction, fibrosis, and arrhythmias in a mouse model of cardiomyopathy secondary to cardiac-specific overexpression of tumor necrosis factor-{alpha} Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1456 - H1467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Milan and C. A. MacRae Animal models for arrhythmias Cardiovasc Res, August 15, 2005; 67(3): 426 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Temple, P. Frias, J. Rottman, T. Yang, Y. Wu, E. E. Verheijck, W. Zhang, C. Siprachanh, H. Kanki, J. B. Atkinson, et al. Atrial Fibrillation in KCNE1-Null Mice Circ. Res., July 8, 2005; 97(1): 62 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Beffagna, G. Occhi, A. Nava, L. Vitiello, A. Ditadi, C. Basso, B. Bauce, G. Carraro, G. Thiene, J. A. Towbin, et al. Regulatory mutations in transforming growth factor-{beta}3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1 Cardiovasc Res, February 1, 2005; 65(2): 366 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Allessie, U. Schotten, S. Verheule, and E. Harks Gene Therapy for Repair of Cardiac Fibrosis: A Long Way to Tipperary Circulation, February 1, 2005; 111(4): 391 - 393. [Full Text] [PDF]
|
|
|
|
|
|
A. Verma, O. M. Wazni, N. F. Marrouche, D. O. Martin, F. Kilicaslan, S. Minor, R. A. Schweikert, W. Saliba, J. Cummings, J. D. Burkhardt, et al. Pre-existent left atrial scarring in patients undergoing pulmonary vein antrum isolation: An independent predictor of procedural failure J. Am. Coll. Cardiol., January 18, 2005; 45(2): 285 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Khan Identifying and understanding the role of pulmonary vein activity in atrial fibrillation Cardiovasc Res, December 1, 2004; 64(3): 387 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nattel Defining "Culprit Mechanisms" in Arrhythmogenic Cardiac Remodeling Circ. Res., June 11, 2004; 94(11): 1403 - 1405. [Full Text] [PDF]
|
|