Reduced Cx43 expression triggers increased fibrosis due to enhanced fibroblast activity

Circulation: Arrhythmia and Electrophysiology

Volumn 5, Issue 2, 2012, Pages 380-390

  Jansen, John A ^a   Van Veen, Toon A B ^a   De Jong, Sanne ^a   Van Der Nagel, Roel ^a   Van Stuijvenberg, Leonie ^a   Driessen, Helen ^a   Labzowski, Ronald ^a   Oefner, Carolin M ^a   Bosch, Astrid A ^a   Nguyen, Tri Q ^a   Goldschmeding, Roel ^a   Vos, Marc A ^a   De Bakker, Jacques M T ^a   Van Rijen, Harold V M ^a  

^a ROYAL NETHERLANDS ACADEMY OF ARTS AND SCIENCES   (Netherlands)

Author keywords

Arrhythmia; Collagen; Connexin43; Electrophysiology mapping; Fibroblast

Indexed keywords

COLLAGEN TYPE 1; COLLAGEN TYPE 1 ALPHA2; CONNEXIN 43; DISCOIDIN DOMAIN RECEPTOR 2; MESSENGER RNA; PROCOLLAGEN PEPTIDE I; PROCOLLAGEN PEPTIDE III; RECEPTOR; UNCLASSIFIED DRUG; COLLAGEN; GJA1 PROTEIN, MOUSE;

AGED; AGING; ANIMAL EXPERIMENT; ANIMAL MODEL; AORTA CONSTRICTION; ARTICLE; CELL ACTIVITY; CONTROLLED STUDY; EPICARDIUM MAPPING; FIBROBLAST; HEART MUSCLE FIBROSIS; HEART VENTRICLE ARRHYTHMIA; ISOLATED HEART; MOUSE; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; ANIMAL; AORTA; CELL PROLIFERATION; COMPARATIVE STUDY; FEMALE; FIBROSIS; HEART ARRHYTHMIA; HEART MUSCLE; HEART MUSCLE CONDUCTION SYSTEM; MALE; METABOLISM; PATHOLOGY; PHYSIOLOGICAL STRESS; PHYSIOLOGY; STENOSIS, OCCLUSION AND OBSTRUCTION;

AGING; ANIMALS; AORTA; ARRHYTHMIAS, CARDIAC; CELL PROLIFERATION; COLLAGEN; CONNEXIN 43; CONSTRICTION, PATHOLOGIC; FEMALE; FIBROBLASTS; FIBROSIS; HEART CONDUCTION SYSTEM; MALE; MICE; MODELS, ANIMAL; MYOCARDIUM; STRESS, PHYSIOLOGICAL;

EID: 84862265492     PISSN: 19413149     EISSN: 19413084     Source Type: Journal    
DOI: 10.1161/CIRCEP.111.966580     Document Type: Article

References (36)

1. Stein M, Noorman M, van Veen TA, Herold E, Engelen MA, Boulaksil M, Antoons G, Jansen JA, van Oosterhout MF, Hauer RN, de Bakker JM, van Rijen HV. Dominant arrhythmia vulnerability of the right ventricle in senescent mice. Heart Rhythm. 2008;5:438-448.
2. Stein M, Boulaksil M, Jansen JA, Herold E, Noorman M, Joles JA, van Veen TA, Houtman MJ, Engelen MA, Hauer RN, de Bakker JM, van Rijen HV. Reduction of fibrosis-related arrhythmias by chronic renin-angiotensin- aldosterone system inhibitors in an aged mouse model. Am J Physiol Heart Circ Physiol. 2010;299:H310-H321.
3. Peters NS. New insights into myocardial arrhythmogenesis: distribution of gap-junctional coupling in normal, ischaemic and hypertrophied human hearts. Clin Sci (Lond). 1996;90:447-452.
4. Kaprielian RR, Gunning M, Dupont E, Sheppard MN, Rothery SM, Underwood R, Pennell DJ, Fox K, Pepper J, Poole-Wilson PA, Severs NJ. Downregulation of immunodetectable connexin43 and decreased gap junction size in the pathogenesis of chronic hibernation in the human left ventricle. Circulation. 1998;97:651-660.
5. Kostin S, Rieger M, Dammer S, Hein S, Richter M, Klovekorn WP, Bauer EP, Schaper J. Gap junction remodeling and altered connexin43 expression in the failing human heart. Mol Cell Biochem. 2003;242: 135-144.
6. La Vecchia L, Ometto R, Bedogni F, Finocchi G, Mosele GM, Bozzola L, Bevilacqua P, Vincenzi M. Ventricular late potentials, interstitial fibrosis, and right ventricular function in patients with ventricular tachycardia and normal left ventricular function. Am J Cardiol. 1998;81: 790-792.
7. Swynghedauw B. Molecular mechanisms of myocardial remodeling. Physiol Rev. 1999;79:215-262.
8. Kawara T, Derksen R, de Groot JR, Coronel R, Tasseron S, Linnenbank AC, Hauer RN, Kirkels H, Janse MJ, de Bakker JM. Activation delay after premature stimulation in chronically diseased human myocardium relates to the architecture of interstitial fibrosis. Circulation. 2001;104: 3069-3075.
9. Winterton SJ, Turner MA, O'Gorman DJ, Flores NA, Sheridan DJ. Hypertrophy causes delayed conduction in human and guinea pig myocardium: accentuation during ischaemic perfusion. Cardiovasc Res. 1994; 28:47-54.
10. McIntyre H, Fry CH. Abnormal action potential conduction in isolated human hypertrophied left ventricular myocardium. J Cardiovasc Electrophysiol. 1997;8:887-894.
11. Levy D, Anderson KM, Savage DD, Balkus SA, Kannel WB, Castelli WP. Risk of ventricular arrhythmias in left ventricular hypertrophy: the Framingham Heart Study. Am J Cardiol. 1987;60:560-565.
12. Saffitz JE. Arrhythmogenic cardiomyopathy and abnormalities of cellto- cell coupling. Heart Rhythm. 2009;6:S62-S65.
13. Oxford EM, Everitt M, Coombs W, Fox PR, Kraus M, Gelzer AR, Saffitz J, Taffet SM, Moise NS, Delmar M. Molecular composition of the intercalated disc in a spontaneous canine animal model of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Heart Rhythm. 2007;4: 1196-1205.
14. Zhang Y, Kanter EM, Laing JG, Aprhys C, Johns DC, Kardami E, Yamada KA. Connexin43 expression levels influence intercellular coupling and cell proliferation of native murine cardiac fibroblasts. Cell Commun Adhes. 2008;15:289-303.
15. van Veen TA, Stein M, Royer A, Le Quang K, Charpentier F, Colledge WH, Huang CL, Wilders R, Grace AA, Escande D, de Bakker JM, van Rijen HV. Impaired impulse propagation in scn5a-knockout mice: combined contribution of excitability, connexin expression, and tissue architecture in relation to aging. Circulation. 2005;112:1927-1935.
16. van Rijen HV, Eckardt D, Degen J, Theis M, Ott T, Willecke K, Jongsma HJ, Opthof T, de Bakker JM. Slow conduction and enhanced anisotropy increase the propensity for ventricular tachyarrhythmias in adult mice with induced deletion of connexin43. Circulation. 2004;109:1048-1055.
17. Eckardt D, Theis M, Degen J, Ott T, van Rijen HV, Kirchhoff S, Kim JS, de Bakker JM, Willecke K. Functional role of connexin43 gap junction channels in adult mouse heart assessed by inducible gene deletion. J Mol Cell Cardiol. 2004;36:101-110.
18. Feil R, Brocard J, Mascrez B, LeMeur M, Metzger D, Chambon P. Ligand-activated site-specific recombination in mice. Proc Natl Acad Sci U S A. 1996;93:10887-10890.
19. Boulaksil M, Winckels SK, Engelen MA, Stein M, van Veen TA, Jansen JA, Linnenbank AC, Bierhuizen MF, Groenewegen WA, van Oosterhout MF, Kirkels JH, de Jonge N, Varro A, Vos MA, de Bakker JM, van Rijen HV. Heterogeneous connexin43 distribution in heart failure is associated with dispersed conduction and enhanced susceptibility to ventricular arrhythmias. Eur J Heart Fail. 2010;12:913-921.
20. Royer A, van Veen TA, Le Bouter S, Marionneau C, Griol-Charhbili V, Leoni AL, Steenman M, van Rijen HV, Demolombe S, Goddard CA, Richer C, Escoubet B, Jarry-Guichard T, Colledge WH, Gros D, de Bakker JM, Grace AA, Escande D, Charpentier F. Mouse model of scn5a-linked hereditary Lenegre's disease: age-related conduction slowing and myocardial fibrosis. Circulation. 2005;111:1738-1746.
21. van Rijen HV, van Veen TA, van Kempen MJ, Wilms-Schopman FJ, Potse M, Krueger O, Willecke K, Opthof T, Jongsma HJ, de Bakker JM. Impaired conduction in the bundle branches of mouse hearts lacking the gap junction protein connexin40. Circulation. 2001;103:1591-1598.
22. van Veen TA, van Rijen HV, Wiegerinck RF, Opthof T, Colbert MC, Clement S, de Bakker JM, Jongsma HJ. Remodeling of gap junctions in mouse hearts hypertrophied by forced retinoic acid signaling. J Mol Cell Cardiol. 2002;34:1411-1423.
23. Alcolea S, Jarry-Guichard T, de Bakker J, Gonzalez D, Lamers W, Coppen S, Barrio L, Jongsma H, Gros D, van Rijen H. Replacement of connexin40 by connexin45 in the mouse: impact on cardiac electrical conduction. Circ Res. 2004;94:100-109.
24. Potse M, Linnenbank AC, Grimbergen CA. Software design for analysis of multichannel intracardial and body surface electrocardiograms. Comput Methods Programs Biomed. 2002;69:225-236.
25. Lammers WJ, Schalij MJ, Kirchhof CJ, Allessie MA. Quantification of spatial inhomogeneity in conduction and initiation of reentrant atrial arrhythmias. Am J Physiol. 1990;259:H1254-H1263.
26. Teunissen BE, Jansen AT, Mutsaers NA, Vuerhard MJ, Vos MA, Bierhuizen MF. Primary structure, organization, and expression of the rat connexin45 gene. DNA Cell Biol. 2007;26:108-115.
27. Xia Y, Lee K, Li N, Corbett D, Mendoza L, Frangogiannis NG. Characterization of the inflammatory and fibrotic response in a mouse model of cardiac pressure overload. Histochem Cell Biol. 2009;131:471-481.
28. Goldsmith EC, Hoffman A, Morales MO, Potts JD, Price RL, McFadden A, Rice M, Borg TK. Organization of fibroblasts in the heart. Dev Dyn. 2004;230:787-794.
29. Bowers SL, Borg TK, Baudino TA. The dynamics of fibroblast- myocytecapillary interactions in the heart. Ann N Y Acad Sci. 2010;1188:143-152.
30. De Mello WC, Specht P. Chronic blockade of angiotensin II at 1-receptors increased cell-to-cell communication, reduced fibrosis and improved impulse propagation in the failing heart. J Renin Angiotensin Aldosterone Syst. 2006;7:201-205.
31. Qu J, Volpicelli FM, Garcia LI, Sandeep N, Zhang J, Marquez-Rosado L, Lampe PD, Fishman GI. Gap junction remodeling and spironolactonedependent reverse remodeling in the hypertrophied heart. Circ Res. 2009; 104:365-371.
32. Stein M, van Veen TA, Remme CA, Boulaksil M, Noorman M, van Stuijvenberg L, van der Nagel R, Bezzina CR, Hauer RN, de Bakker JM, van Rijen HV. Combined reduction of intercellular coupling and membrane excitability differentially affects transverse and longitudinal cardiac conduction. Cardiovasc Res. 2009;83:52-60.
33. Beauchamp P, Choby C, Desplantez T, de Peyer K, Green K, Yamada KA, Weingart R, Saffitz JE, Kleber AG. Electrical propagation in synthetic ventricular myocyte strands from germline connexin43 knockout mice. Circ Res. 2004;95:170-178.
34. Thomas SP, Kucera JP, Bircher-Lehmann L, Rudy Y, Saffitz JE, Kleber AG. Impulse propagation in synthetic strands of neonatal cardiac myocytes with genetically reduced levels of connexin43. Circ Res. 2003; 92:1209-1216.
35. Marionneau C, Brunet S, Flagg TP, Pilgram TK, Demolombe S, Nerbonne JM. Distinct cellular and molecular mechanisms underlie functional remodeling of repolarizing K- currents with left ventricular hypertrophy. Circ Res. 2008;102:1406-1415.
36. Wit AL, Dillon SM. Anisotropic reentry. In: Shenasa M, Borggrefe M, Breithardt G, eds. Cardiac Mapping. New York: Futura Publishing; 1993;127-154.