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Thorac Cardiovasc Surg 2014; 62(07): 547-553
DOI: 10.1055/s-0034-1372334
Original Basic Science
Georg Thieme Verlag KG Stuttgart · New York

Body Mass Index Affects Connexin43 Remodeling in Patients with Atrial Fibrillation

Susanne Rothe
1   Clinic for Cardiac Surgery, Heart Centre Leipzig, University Leipzig, Leipzig, Germany
,
Andrea Busch
1   Clinic for Cardiac Surgery, Heart Centre Leipzig, University Leipzig, Leipzig, Germany
,
Hartmuth Bittner
2   Department of Transplantation, Florida Hospital, Orlando, Florida, United States
,
Martin Kostelka
1   Clinic for Cardiac Surgery, Heart Centre Leipzig, University Leipzig, Leipzig, Germany
,
Pascal Maria Dohmen
1   Clinic for Cardiac Surgery, Heart Centre Leipzig, University Leipzig, Leipzig, Germany
,
Friedrich-Wilhelm Mohr
1   Clinic for Cardiac Surgery, Heart Centre Leipzig, University Leipzig, Leipzig, Germany
,
Stefan Dhein
1   Clinic for Cardiac Surgery, Heart Centre Leipzig, University Leipzig, Leipzig, Germany
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Weitere Informationen

Publikationsverlauf

13. Dezember 2013

25. Januar 2014

Publikationsdatum:
08. April 2014 (online)

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Abstract

Background Increased body mass index (BMI) is often found to be a risk factor for cardiac disease. However, it is unclear whether BMI also affects the gap junction remodeling process in atrial fibrillation (AF). The aim of the study was to see if BMI can influence the connexin43 (Cx43) distribution in patients with sinus rhythm (SR) and AF.

Methods We investigated a total of 51 white Caucasian patients of both gender (mean age: 69 years, 30% diabetes mellitus, ejection fraction [EF] > 50%) with SR or AF, with either BMI < 27 or ≥ 27 undergoing cardiac surgery for mitral valve repair, aortic valve repair, or coronary heart disease. We obtained human right atrial tissue for immunohistochemistry and investigated the CX43-positive polar and lateral membrane length in the different BMI (BMI < 27, BMI ≥ 27) and rhythm groups (SR or AF).

Results In lean SR patients, Cx43 (BMI < 27) was found mainly at the cell poles while only 2% of the lateral membrane stained positive for Cx43. In obese SR patients (BMI > 27), 6.7 ± 0.7% of the lateral membrane was positive (p < 0.05). In AF generally, there was significantly more lateral Cx43 staining, which was significantly enhanced in obese AF patients. In lean AF patients, lateral Cx43 positivity increased to 14 ± 1% (p < 0.05), while in BMI > 27 AF patients, this was significantly enhanced to 22 ± 2% (p < 0.05). The BMI effect was independent from left atrial diameter, EF, and comorbidity.

Conclusions Enhanced BMI is associated with increased remodeling effects of AF on irregular Cx43 distribution.

Keywords

body mass index - atrial fibrillation - remodeling - connexin - gap junctions
 

  • References

  • 1 Simpson I, Rose B, Loewenstein WR. Size limit of molecules permeating the junctional membrane channels. Science 1977; 195 (4275) 294-296
    CrossrefPubMedGoogle Scholar
  • 2 Weingart R, Maurer P. Action potential transfer in cell pairs isolated from adult rat and guinea pig ventricles. Circ Res 1988; 63 (1) 72-80
    CrossrefPubMedGoogle Scholar
  • 3 Beauchamp P, Choby C, Desplantez T , et al. Electrical propagation in synthetic ventricular myocyte strands from germline connexin43 knockout mice. Circ Res 2004; 95 (2) 170-178
    CrossrefPubMedGoogle Scholar
  • 4 Unger VM, Kumar NM, Gilula NB, Yeager M. Three-dimensional structure of a recombinant gap junction membrane channel. Science 1999; 283 (5405) 1176-1180
    CrossrefPubMedGoogle Scholar
  • 5 Dhein S. Gap junction channels in the cardiovascular system: pharmacological and physiological modulation. Trends Pharmacol Sci 1998; 19 (6) 229-241
    CrossrefPubMedGoogle Scholar
  • 6 Polontchouk L, Haefliger JA, Ebelt B , et al. Effects of chronic atrial fibrillation on gap junction distribution in human and rat atria. J Am Coll Cardiol 2001; 38 (3) 883-891
    CrossrefPubMedGoogle Scholar
  • 7 Kostin S, Klein G, Szalay Z, Hein S, Bauer EP, Schaper J. Structural correlate of atrial fibrillation in human patients. Cardiovasc Res 2002; 54 (2) 361-379
    CrossrefPubMedGoogle Scholar
  • 8 Wetzel U, Boldt A, Lauschke J , et al. Expression of connexins 40 and 43 in human left atrium in atrial fibrillation of different aetiologies. Heart 2005; 91 (2) 166-170
    CrossrefPubMedGoogle Scholar
  • 9 Kostin S, Dammer S, Hein S, Klövekorn WP, Bauer EP, Schaper J. Connexin 43 expression and distribution in compensated and decompensated cardiac hypertrophy in patients with aortic stenosis. Cardiovasc Res 2004; 62 (2) 426-436
    CrossrefPubMedGoogle Scholar
  • 10 Salameh A, Wustmann A, Karl S , et al. Cyclic mechanical stretch induces cardiomyocyte orientation and polarization of the gap junction protein connexin43. Circ Res 2010; 106 (10) 1592-1602
    CrossrefPubMedGoogle Scholar
  • 11 Dupont E, Matsushita T, Kaba RA , et al. Altered connexin expression in human congestive heart failure. J Mol Cell Cardiol 2001; 33 (2) 359-371
    CrossrefPubMedGoogle Scholar
  • 12 Kaprielian RR, Gunning M, Dupont E , et al. Downregulation of immunodetectable connexin43 and decreased gap junction size in the pathogenesis of chronic hibernation in the human left ventricle. Circulation 1998; 97 (7) 651-660
    CrossrefPubMedGoogle Scholar
  • 13 Salameh A, Frenzel C, Boldt A , et al. Subchronic alpha- and beta-adrenergic regulation of cardiac gap junction protein expression. FASEB J 2006; 20 (2) 365-367
    PubMedGoogle Scholar
  • 14 Salameh A, Dhein S. Adrenergic control of cardiac gap junction function and expression. Naunyn Schmiedebergs Arch Pharmacol 2011; 383 (4) 331-346
    CrossrefPubMedGoogle Scholar
  • 15 Polontchouk L, Ebelt B, Jackels M, Dhein S. Chronic effects of endothelin 1 and angiotensin II on gap junctions and intercellular communication in cardiac cells. FASEB J 2002; 16 (1) 87-89
    PubMedGoogle Scholar
  • 16 Dhein S, Rothe S, Busch A , et al. Effects of metoprolol therapy on cardiac gap junction remodelling and conduction in human chronic atrial fibrillation. Br J Pharmacol 2011; 164 (2b) 607-616
    CrossrefPubMedGoogle Scholar
  • 17 Overvad TF, Rasmussen LH, Skjøth F, Overvad K, Lip GY, Larsen TB. Body mass index and adverse events in patients with incident atrial fibrillation. Am J Med 2013; 126 (7) e9-e17
    PubMedGoogle Scholar
  • 18 Murphy NF, MacIntyre K, Stewart S, Hart CL, Hole D, McMurray JJV. Long-term cardiovascular consequences of obesity: 20-year follow-up of more than 15 000 middle-aged men and women (the Renfrew-Paisley study). Eur Heart J 2006; 27 (1) 96-106
    PubMedGoogle Scholar
  • 19 Frost L, Hune LJ, Vestergaard P. Overweight and obesity as risk factors for atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study. Am J Med 2005; 118 (5) 489-495
    CrossrefPubMedGoogle Scholar
  • 20 Wang TJ, Parise H, Levy D , et al. Obesity and the risk of new-onset atrial fibrillation. JAMA 2004; 292 (20) 2471-2477
    CrossrefPubMedGoogle Scholar
  • 21 Henry WL, Morganroth J, Pearlman AS , et al. Relation between echocardiographically determined left atrial size and atrial fibrillation. Circulation 1976; 53 (2) 273-279
    CrossrefPubMedGoogle Scholar
  • 22 Satoh T, Zipes DP. Unequal atrial stretch in dogs increases dispersion of refractoriness conducive to developing atrial fibrillation. J Cardiovasc Electrophysiol 1996; 7 (9) 833-842
    CrossrefPubMedGoogle Scholar
  • 23 Parkash R, Green MS, Kerr CR , et al; Canadian Registry of Atrial Fibrillation. The association of left atrial size and occurrence of atrial fibrillation: a prospective cohort study from the Canadian Registry of Atrial Fibrillation. Am Heart J 2004; 148 (4) 649-654
    CrossrefPubMedGoogle Scholar
  • 24 Boldt A, Wetzel U, Lauschke J , et al. Fibrosis in left atrial tissue of patients with atrial fibrillation with and without underlying mitral valve disease. Heart 2004; 90 (4) 400-405
    CrossrefPubMedGoogle Scholar
  • 25 Lin Y-K, Chen Y-C, Chen J-H, Chen S-A, Chen Y-J. Adipocytes modulate the electrophysiology of atrial myocytes: implications in obesity-induced atrial fibrillation. Basic Res Cardiol 2012; 107 (5) 293
    CrossrefPubMedGoogle Scholar
  • 26 Kwak BR, Pepper MS, Gros DB, Meda P. Inhibition of endothelial wound repair by dominant negative connexin inhibitors. Mol Biol Cell 2001; 12 (4) 831-845
    CrossrefPubMedGoogle Scholar
  • 27 Pfannmüller B, Boldt A, Reutemann A , et al. Gender-specific remodeling in atrial fibrillation?. Thorac Cardiovasc Surg 2013; 61 (1) 66-73
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 28 Canoy D, Cairns BJ, Balkwill A , et al; Million Women Study Collaborators. Coronary heart disease incidence in women by waist circumference within categories of body mass index. Eur J Prev Cardiol 2013; 20 (5) 759-762
    CrossrefPubMedGoogle Scholar
  • 29 Burke AP, Litovsky S, Virmani R. Lipomatous hypertrophy of the atrial septum presenting as a right atrial mass. Am J Surg Pathol 1996; 20 (6) 678-685
    CrossrefPubMedGoogle Scholar
  • 30 Abed HS, Wittert GA. Obesity and atrial fibrillation. Obes Rev 2013; 14 (11) 929-938
    CrossrefPubMedGoogle Scholar
  • 31 Zacharias A, Schwann TA, Riordan CJ, Durham SJ, Shah AS, Habib RH. Obesity and risk of new-onset atrial fibrillation after cardiac surgery. Circulation 2005; 112 (21) 3247-3255
    CrossrefPubMedGoogle Scholar
  • 32 Tsang TS, Barnes ME, Miyasaka Y , et al. Obesity as a risk factor for the progression of paroxysmal to permanent atrial fibrillation: a longitudinal cohort study of 21 years. Eur Heart J 2008; 29 (18) 2227-2233
    CrossrefPubMedGoogle Scholar
  • 33 Schnabel RB, Sullivan LM, Levy D , et al. Development of a risk score for atrial fibrillation (Framingham Heart Study): a community-based cohort study. Lancet 2009; 373 (9665) 739-745
    CrossrefPubMedGoogle Scholar
  • 34 Magnani JW, Hylek EM, Apovian CM. Obesity begets atrial fibrillation: a contemporary summary. Circulation 2013; 128 (4) 401-405
    CrossrefPubMedGoogle Scholar
  • 35 Lin YK, Chen YJ, Chen SA. Potential atrial arrhythmogenicity of adipocytes: implications for the genesis of atrial fibrillation. Med Hypotheses 2010; 74 (6) 1026-1029
    CrossrefPubMedGoogle Scholar
  • 36 Tsao HM, Hu WC, Wu MH , et al. Quantitative analysis of quantity and distribution of epicardial adipose tissue surrounding the left atrium in patients with atrial fibrillation and effect of recurrence after ablation. Am J Cardiol 2011; 107 (10) 1498-1503
    CrossrefPubMedGoogle Scholar
  • 37 Al Chekakie MO, Welles CC, Metoyer R , et al. Pericardial fat is independently associated with human atrial fibrillation. J Am Coll Cardiol 2010; 56 (10) 784-788
    CrossrefPubMedGoogle Scholar
  • 38 Abed HS, Wittert GA, Leong DP , et al. Effect of weight reduction and cardiometabolic risk factor management on symptom burden and severity in patients with atrial fibrillation: a randomized clinical trial. JAMA 2013; 310 (19) 2050-2060
    CrossrefPubMedGoogle Scholar
  • 39 Beardslee MA, Laing JG, Beyer EC, Saffitz JE. Rapid turnover of connexin43 in the adult rat heart. Circ Res 1998; 83 (6) 629-635
    CrossrefPubMedGoogle Scholar
  • 40 Weber PA, Chang HC, Spaeth KE, Nitsche JM, Nicholson BJ. The permeability of gap junction channels to probes of different size is dependent on connexin composition and permeant-pore affinities. Biophys J 2004; 87 (2) 958-973
    CrossrefPubMedGoogle Scholar
  • 41 Haubrich S, Schwarz HJ, Bukauskas F , et al. Incompatibility of connexin 40 and 43 Hemichannels in gap junctions between mammalian cells is determined by intracellular domains. Mol Biol Cell 1996; 7 (12) 1995-2006
    CrossrefPubMedGoogle Scholar