Basic Research in Cardiology

, Volume 101, Issue 3, pp 261–267

ACE–inhibitor treatment attenuates atrial structural remodeling in patients with lone chronic atrial fibrillation

  • A. Boldt
  • A. Scholl
  • J. Garbade
  • M. E. Resetar
  • F. W. Mohr
  • J. F. Gummert
  • St. Dhein
ORIGINAL CONTRIBUTION

Abstract

Objective

Chronic atrial fibrillation (AF) is characterized by a remodeling process which involves the development of fibrosis. Since angiotensin II has been suspected to be involved in this process, the aim of our study was to investigate a possible influence of an ACE–I therapy in patients with chronic AF regarding the occurrence of left atrial structural remodeling.

Methods

Atrial tissue samples were obtained from patients with lone chronic AF or sinus rhythm (SR). Collagen I, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) protein expression were measured by quantitative Western Blotting techniques and calculated as mean ± SEM. Histological tissue samples were used for calculating microvessel density (microvessel/mm2 ± SEM).

Results

In AF, the collagen amount was higher (1.78 ± 0.21; p = 0.01) vs. SR (0.37 ± 0.07) accompanied by declining microcapillary density (AF: 145 ± 13 vs. SR: 202 ± 9; p = 0.01). Additionally, a negative correlation (p = 0.01) between collagen content and microcapillary density was observed. To investigate the influence of an ACE–I therapy on this remodeling process, patient groups were divided into AF and SR both with or without ACE–I. Interestingly, there was a significantly lower expression of collagen I in AF with ACE–I (1.04 ± 0.26) vs. AF without ACE–I treatment (2.07 ± 0.24, p = 0.02). The microcapillaries were not diminished in AF with ACE–I (180 ± 15) vs. SR with ACE–I (196 ± 9), but there was a significant rarification in AF without ACE–I (123 ± 18; p = 0.03). The expression of VEGF and bFGF did not reveal any significant differences.

Conclusion

In patients undergoing ACE–I treatment: atrial structural remodeling was attenuated and the loss of atrial microcapillaries was prevented.

Key words

arrhythmia growth factor collagen ACE angiogenesis 

Abbreviations

ACE-I

angiotensin converting enzyme inhibitor

AF

atrial fibrillation

bFGF

basic fibroblast growth factor lone

CAF

lone chronic atrial fibrillation

SR

sinus rhythm

VEGF

vascular endothelial growth factor

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Allessie M, Ausma A, Schotten U (2002) Electrical, contractile and structural remodeling promote stability of atrial fibrillation. Cardiovasc Res 54:230–246CrossRefPubMedGoogle Scholar
  2. 2.
    Belichard P, Savard P, Cardinal R et al. (1994) Markedly different effects on ventricular remodeling result in a decrease in inducibility of ventricular arrhythmias. J Am Coll Cardiol 23:505–513PubMedGoogle Scholar
  3. 3.
    Boldt A, Wetzel U, Lauschke J et al. (2004) Fibrosis in left atrial tissue of patients with atrial fibrillation with and without underlying mitral valve disease. Heart 90:400–405CrossRefPubMedGoogle Scholar
  4. 4.
    Boldt A, Wetzel U, Weigl J et al. (2003) Expression of angiotensin II receptors in human left and right atrial tissue in atrial fibrillation with and without underlying mitral valve disease. J Am Coll Cardiol 42:1785–1792CrossRefPubMedGoogle Scholar
  5. 5.
    Dai Y, Wang X, Cao L, Yang M, Wu T (2004) Expression of extracellular signalregulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation. J Huazhong Univ Sci Technolog Med Sci 24:32–36PubMedGoogle Scholar
  6. 6.
    Goette A, Arndt M, Roecken C et al. (2000) Regulation of angiotensin II receptor subtypes during atrial fibrillation in humans. Circulation 101:2678–2681PubMedGoogle Scholar
  7. 7.
    Goette A, Staack T, Rocken C et al. (2000) Increased expression of extracellular signal-regulated kinase and angiotensinconverting enzyme in human atria during atrial fibrillation. J Am Coll Cardiol 35:1669–1677CrossRefPubMedGoogle Scholar
  8. 8.
    Grammer JB, Bohm J, Dufour A et al. (2005) Atrial fibrosis in heart surgery patients. Decreased collagen III/I ratio in postoperative atrial fibrillation. Basic Res Cardiol 100:288–294CrossRefPubMedGoogle Scholar
  9. 9.
    Kottkamp H, Hindricks G, Autschbach R, et al. (2002) Specific linear left atrial lesions in atrial fibrillation: intraoperative radiofrequency ablation using minimally invasive surgical techniques. J Am Coll Cardiol 40:475–480CrossRefPubMedGoogle Scholar
  10. 10.
    Li D, Fareh S, Leung TK et al. (1999) Promotion of atrial fibrillation by heart failure in dogs. Atrial remodeling of a different sorts. Circulation 100:87–95PubMedGoogle Scholar
  11. 11.
    Li D, Shinagawa K, Pang L et al. (2001) Effects of angiotensin converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure. Circulation 104:2608–2614PubMedGoogle Scholar
  12. 12.
    Nattel S (2002) New ideas about atrial fibrillation 50 years on. Nature 415:219–226CrossRefPubMedGoogle Scholar
  13. 13.
    Sabbah HN, Sharov VG, Lesch M, Goldstein S (1995) Progression of heart failure: a role for interstitional fibrosis. Mol Cell Biochem 147:29–34CrossRefPubMedGoogle Scholar
  14. 14.
    Sakabe M, Fujiki A, Nishida K et al. (2004) Enalapril prevents perpetuation of atrial fibrillation by suppressing atrial fibrosis and over-expression of connexin 43 in a canine model of atrial pacinginduced left ventricular dysfunction. J Cardiovasc Pharmacol 43:851–859PubMedGoogle Scholar
  15. 15.
    Shi Y, Li D, Tardif J-C, Nattel S (2002) Enalapril effects on atrial remodeling and atrial fibrillation in experimental congestive heart failure. Cardiovasc Res 54:456–461CrossRefPubMedGoogle Scholar
  16. 16.
    Youn TJ, Kim HS, Oh BH (1999) Ventricular remodeling and transforming growth factor-beta 1 mRNA expression after nontransmural myocardial infarction in rats: effects of angiotensin converting enzyme inhibition and angiotensin II type 1receptor blockade. Basic Res Cardiol 94:246–253CrossRefPubMedGoogle Scholar
  17. 17.
    Van Noord T, Crijns HGJM, van den Berg MP et al. (2005) Pretreatment with ACE inhibitors improves acute outcome of electrical cardioversion in patients with persistent atrial fibrillation. BMC Cardiovasc Disord 5:3CrossRefPubMedGoogle Scholar
  18. 18.
    Wang JM, Wang Y, Zhu ZS et al. (2004) Diverse effects of long-term treatment with imidapril and irbesartan on cell growth signal, apoptosis and collagen type I expression in the left ventricle of spontaneously hypertensive rats. Life Sci 75:407–420CrossRefPubMedGoogle Scholar

Copyright information

© Steinkopff-Verlag 2005

Authors and Affiliations

  • A. Boldt
    • 1
  • A. Scholl
    • 1
  • J. Garbade
    • 1
  • M. E. Resetar
    • 1
  • F. W. Mohr
    • 1
  • J. F. Gummert
    • 1
  • St. Dhein
    • 1
  1. 1.University of Leipzig—Heart CenterDepartment of Cardiac SurgeryLeipzigGermany

Personalised recommendations