Механизмы, клиническая значимость и взаимоотношение тканевого фиброза и фибрилляции предсердий = Mechanisms, clinical significance and relationship of tissue fibrosis and atrial fibrillation = Механізми, клінічна значущість та взаємовідношення тканинного фіброзу і фібриляції передсердь

A. I. Gozhenko, E. M. Levchenko, V. V. Goriachyi, A. V. Goriachyi


Atrial fibrillation (AF) is the most common heart rhythm disorder in clinical practice. Today proved that traditional pharmacologic therapies are effective in patients with paroxysmal atrial fibrillation with no structural disorders of the myocardium. Data from clinical and experimental studies have shown the important role of the structural remodeling in the formation of the substrate of atrial fibrillation, producing fibrosis that alters the composition and function of the atrial tissue. The exact mechanism underlying atrial fibrosis is not fully elucidated, but recent experimental and clinical studies have provided important data. It has been shown that in the process of formation and propagation of fibrosis involved number of different signaling systems, including angiotensin-2 and related mediators. This article provides an overview of the current understanding of the formation of atrial fibrillation substrate by fibrosis remodeling. Sum-date data on the mechanisms underlying the fibrosis and progression as well as brightly lit modern therapeutic approaches aimed at reducing structural remodeling to prevent AF.


фибрилляция предсердий, фиброз, структурное ремоделирование, atrial fibrillation, fibrosis, structural remodeling

Full Text:



Walker AM, Bennett D. Epidemiology and outcomes in patients with atrial fibrillation in the United States. Heart Rhythm 2008 October;5(10):1365-72.

Zhou Z, Hu D. An epidemiological study on the prevalence of atrial fibrillation in the Chinese population of mainland China. J Epidemiol 2008;18(5):209-16.

Kannel WB, Benjamin EJ. Status of the epidemiology of atrial fibrillation. Med Clin North Am 2008 January;92(1):17-40, ix

Li D, Fareh S, Leung TK, Nattel S. Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort. Circulation 1999;100:87–95.

Dorn G.W. II, Force T.; Protein kinase cascade in the regulation of cardiac hypertrophy. J Clin Invest. 2005;115:527-537.

Nishida K., Qi X.Y., Wakili R., et al; Mechanisms of atrial tachyarrhythmias associated with coronary artery occlusion in a chronic canine model. Circulation. 2011;123:137-146.

Cardin S., Guasch E., Luo X., et al; Role for microRNA-21 in atrial profibrillatory fibrotic remodeling associated with experimental postinfarction heart failure. Circ Arrhythm Electrophysiol. 2012;5:1027-1035.

Abonnenc M., Nabeebaccus A.A., Mayr U., et al; Extracellular matrix secretion by cardiac fibroblasts: role of microRNA-29b and microRNA-30c. Circ Res. 2013;113:1138-1147.

Ohtani K, Yutani C, Nagata S, Koretsune Y, Hori M, Kamada T. High prevalence of atrial fibrosis in patients with dilated cardiomy- opathy. J Am Coll Cardiol 1995;25:1162–9.

Bailey GW, Braniff BA, Hancock EW, Cohn KE. Relation of left atrial pathology to atrial fibrillation in mitral valvular disease. Ann Intern Med 1968;69:13–20.

Sinno H, Derakhchan K, Libersan D, Merhi Y, Leung TK, Nattel S. Atrial ischemia promotes atrial fibrillation in dogs. Circulation 2003;107:1930 – 6.

Kostin S, Klein G, Szalay Z, Hein S, Bauer EP, Schaper J. Structural correlate of atrial fibrillation in human patients. Cardiovasc Res 2002;54:361–79.

Frustaci A, Chimenti C, Bellocci F, Morgante E, Russo MA, Maseri A. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 1997;96:1180–4.

Burstein B., Nattel S.; Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol. 2008;51:802-809.

Qi X.Y., Yeh Y.H., Xiao L., et al; Cellular signaling underlying atrial tachycardia remodeling of L-type calcium current. Circ Res. 2008;103:845-854.

Armstrong PW, Stopps TP, Ford SE, De Bold AJ. Rapid ventricular pacing in the dog: pathophysiologic studies of heart failure. Circula- tion 1986;74:1075–84.

Derakhchan K, Li D, Courtemanche M, et al. Method for simulta- neous epicardial and endocardial mapping of in vivo canine heart: application to atrial conduction properties and arrhythmia mecha- nisms. J Cardiovasc Electrophysiol 2001;12:548–55.

Fenelon G, Shepard RK, Stambler BS. Focal origin of atrial tachycardia in dogs with rapid ventricular pacing-induced heart failure. J Cardiovasc Electrophysiol 2003;14:1093–102.

Voigt N., Heijman J., Wang Q., et al; Cellular and molecular mechanisms of atrial arrhythmogenesis in patients with paroxysmal atrial fibrillation. Circulation. 2013;129:145-156.

Cardin S, Li D, Thorin-Trescases N, Leung TK, Thorin E, Nattel S. Evolution of the atrial fibrillation substrate in experimental conges- tive heart failure: angiotensin-dependent and -independent pathways. Cardiovasc Res 2003;60:315–25.

Barth AS, Merk S, Arnoldi E, et al. Reprogramming of the human atrial transcriptome in permanent atrial fibrillation: expression of a ventricular-like genomic signature. Circ Res 2005;96:1022–9.

Li D, Melnyk P, Feng J, et al. Effects of experimental heart failure on atrial cellular and ionic electrophysiology. Circulation 2000;101: 2631– 8.

Harada M., Luo X., Murohara T., Yang B., Nattel S.; MicroRNA regulation and cardiac calcium signaling: role in cardiac disease and therapeutic potential. Circ Res. 2014;114:689-705.

Tsai C.T., Tseng C.D., Hwang J.J., et al; Tachycardia of atrial myocytes induces collagen expression in atrial fibroblasts through transforming growth factor β1. Cardiovasc Res. 2011;89:805-815.

Rucker-Martin C, Milliez P, Tan S, et al. Chronic hemodynamic overload of the atria is an important factor for gap junction remod- eling in human and rat hearts. Cardiovasc Res 2006;72:69–79.

Makary S., Voigt N., Maguy A., et al; Differential protein kinase C isoform regulation and increased constitutive activity of acetylcholine-regulated potassium channels in atrial remodeling. Circ Res. 2011;109:1031-1043.

Dobaczewski M., Chen W., Frangogiannis N.G.; Transforming growth factor (TGF)-β in cardiac remodeling. J Mol Cell Cardiol. 2011;51:600-606.

Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 2005;45:1243–8.

Weber KT, Sun Y, Katwa LC, Cleutjens JP. Tissue repair and angiotensin II generated at sites of healing. Basic Res Cardiol 1997;92:75– 8.

Xiao HD, Fuchs S, Campbell DJ, et al. Mice with cardiac-restricted angiotensin-converting enzyme (ACE) have atrial enlargement, car- diac arrhythmia, and sudden death. Am J Pathol 2004;165:1019 –32.

Inoue N, Ohkusa T, Nao T, et al. Rapid electrical stimulation of

contraction modulates gap junction protein in neonatal rat cultured cardiomyocytes: involvement of mitogen-activated protein kinases and effects of angiotensin II-receptor antagonist. J Am Coll Cardiol 2004;44:914 –22.

Lee AA, Dillmann WH, McCulloch AD, Villarreal FJ. Angiotensin II stimulates the autocrine production of transforming growth factor- beta 1 in adult rat cardiac fibroblasts. J Mol Cell Cardiol 1995;27: 2347–57.

Kim S, Ohta K, Hamaguchi A, Yukimura T, Miura K, Iwao H. Angiotensin II induces cardiac phenotypic modulation and remod- eling in vivo in rats. Hypertension 1995;25:1252–9.

Everett AD, Tufro-McReddie A, Fisher A, Gomez RA. Angiotensin receptor regulates cardiac hypertrophy and transforming growth factor-beta 1 expression. Hypertension 1994;23:587–92.

Hao J, Wang B, Jones SC, Jassal DS, Dixon IM. Interaction between angiotensin II and SMAD proteins in fibroblasts in failing heart and in vitro. Am J Physiol Heart Circ Physiol 2000;279:H3020–30.

63. Nakajima H, Nakajima HO, Salcher O, et al. Atrial but not ventricular fibrosis in mice expressing a mutant transforming growth factor-beta(1) transgene in the heart. Circ Res 2000;86:571–9.

Kawamura M., Munetsugu Y., Kawasaki S., et al; Type III procollagen-N-peptide as a predictor of persistent atrial fibrillation recurrence after cardioversion. Europace. 2012;14:1719-1725.

Li N., Chiang D.Y., Wang S., et al; Ryanodine-receptor mediated calcium leak drives progressive development of an atrial fibrillation substrate in a transgenic mouse model. Circulation. 2014;129:1276-1285.

Hinescu ME, Gherghiceanu M, Mandache E, Ciontea SM, Popescu LM. Interstitial Cajal-like cells (ICLC) in atrial myocardium: ultra- structural and immunohistochemical characterization. J Cell Mol Med 2006;10:243–57.

Yokoyama T, Sekiguchi K, Tanaka T, et al. Angiotensin II and mechanical stretch induce production of tumor necrosis factor in cardiac fibroblasts. Am J Physiol 1999;276:H1968–76.

Riser BL, Cortes P, Heilig C, et al. Cyclic stretching force selectively up-regulates transforming growth factor-beta isoforms in cultured rat mesangial cells. Am J Pathol 1996;148:1915–23.

Kirchhof P., Marijon E., Fabritz L., et al; Overexpression of cAMP-response element modulator causes abnormal growth and development of the atrial myocardium resulting in a substrate for sustained atrial fibrillation in mice. Int J Cardiol. 2013;166:366-374.

Kamkin A, Kiseleva I, Lozinsky I, Scholz H. Electrical interaction of mechanosensitive fibroblasts and myocytes in the heart. Basic Res Cardiol 2005;100:337–45.

Cleutjens JP, Verluyten MJ, Smiths JF, Daemen MJ. Collagen remodeling after myocardial infarction in the rat heart. Am J Pathol 1995;147:325–38.

Zou Y, Akazawa H, Qin Y, et al. Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II. Nat Cell Biol 2004;6:499–506.

Malhotra R, Sadoshima J, Brosius FC, III, Izumo S. Mechanical stretch and angiotensin II differentially upregulate the renin- angiotensin system in cardiac myocytes in vitro. Circ Res 1999;85: 137– 46.

Burstein B, Qi XY, Yeh YH, Calderone A, Nattel S. Atrial cardiomyocyte tachycardia alters cardiac fibroblast function: a novel consideration in atrial remodeling. Cardiovasc Res 2007;76:442–52.

Pathak M, Sarkar S, Vellaichamy E, Sen S. Role of myocytes in myocardial collagen production. Hypertension 2001;37:833–40.

Rucker-Martin C, Pecker F, Godreau D, Hatem SN. Dedifferenti- ation of atrial myocytes during atrial fibrillation: role of fibroblast proliferation in vitro. Cardiovasc Res 2002;55:38 –52.

Bikou O., Thomas D., Trappe K., et al; Connexin 43 gene therapy prevents persistent atrial fibrillation in a porcine model. Cardiovasc Res. 2011;92:218-225.

Healey JS, Baranchuk A, Crystal E, et al. Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angio- tensin receptor blockers: a meta-analysis. J Am Coll Cardiol 2005; 45:1832–9.

Nomura M, Kawano T, Nakayasu K, Nakaya Y. The effects of losartan on signal-averaged P wave in patients with atrial fibrillation. Int J Cardiol 2007 May 15; [Epub ahead of print].

Milliez P, Deangelis N, Rucker-Martin C, et al. Spironolactone reduces fibrosis of dilated atria during heart failure in rats with myocardial infarction. Eur Heart J 2005;26:2193–9.

Lee KW, Everett TH, Rahmutula D, et al. Pirfenidone prevents the development of a vulnerable substrate for atrial fibrillation in a canine model of heart failure. Circulation 2006;114:1703–12.

Shiroshita-Takeshita A, Brundel BJ, Burstein B, et al. Effects of simvastatin on the development of the atrial fibrillation substrate in dogs with congestive heart failure. Cardiovasc Res 2007;74:75–84.

Sakabe M, Shiroshita-Takeshita A, Maguy A, et al. Omega-3 polyunsaturated fatty acids prevent atrial fibrillation associated with heart failure but not atrial tachycardia remodeling. Circulation 2007;116:2101–9.

Nishida K., Maguy A., Sakabe M., Comtois P., Inoue H., Nattel S.; The role of pulmonary veins versus autonomic ganglia in different experimental substrates of canine atrial fibrillation. Cardiovasc Res. 2011;89:825-833.

Levy BI. Can angiotensin II type 2 receptors have deleterious effects in cardiovascular disease? Implications for therapeutic blockade of the renin-angiotensin system. Circulation 2004;109:8–13.

Leone O, Boriani G, Chiappini B, et al. Amyloid deposition as a cause of atrial remodeling in persistent valvular atrial fibrillation. Eur Heart J 2004;25:1237– 41.

Saito T, Tamura K, Uchida D, et al. Histopathological features of the resected left atrial appendage as predictors of recurrence after surgery for atrial fibrillation in valvular heart disease. Circ J 2007;71:70 – 8.

Griffin WR, Nelson HG, Seal JR. Hemochromatosis with auricular fibrillation; a case report. Am Heart J 1950;39:904 – 812.

DOI: http://dx.doi.org/10.5281/zenodo.192387


  • There are currently no refbacks.

Copyright (c) 2016 © The Author (s) 2016

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Journal of Education, Health and Sport formerly Journal of Health Sciences

Declaration on the original version.

Editors indicates that the main version of the magazine is to issue a "electronic".

The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019.

1223 Journal of Education, Health and Sport eISSN 2391-8306 7

ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

Archives 2011 - 2014

PBN 2011 - 2014


POL-index 2011 - 2014


BASE 2011 - 2014




Indexed in Bases, Bazy indeksacyjne: ERIH Plus, Worldcat, PBN/POL-Index, ICI Journals Master List, Directory of Open Access Journals (DOAJ), ZBD, Ulrich's periodicals, Google Scholar, Polska Bibliografia Lekarska

US NLM = 101679844

101679844 - NLM Catalog Result - NCBI


Find a library that holds this journal: http://worldcat.org/issn/23918306

Journal Language(s): English 

PBN Poland






Redaction, Publisher and Editorial Office

Instytut Kultury Fizycznej Uniwersytet Kazimierza Wielkiego w Bydgoszczy, Institute of Physical Education Kazimierz Wielki University in Bydgoszcz, Poland 85-091 Bydgoszcz ul. Sportowa 2  www.ukw.edu.pl Copyright by Instytut Kultury Fizycznej UKW w Bydgoszczy http://ojs.ukw.edu.pl/index.php/johs  Open Access ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

The journal has been approved for inclusion in ERIH PLUS.

The ERIH PLUS listing of the journal is available at https://dbh.nsd.uib.no/publiseringskanaler/erihplus/periodical/info?id=485984

SIC Science citation index (calculated on the basis of TCI and Page Rank) 0

Russian Impact factor 0.16

Indexed in Index Copernicus Journals Master List.


ICV 2018 = 95.95 ICV 2017 = 91.30 ICV 2016 = 84.69 ICV 2015 = 93.34 ICV 2014 = 89.51 Standardized Value: 8.27 ICV 2013: 7.32 ICV 2012: 6.41 ICV 20115.48

The InfoBase Index IBI Factor for the year 2015 is 3.56 in InfoBase Index.com.

Website: www.infobaseindex.com

Universal Impact Factor 1.78 for year 2012. (http://www.uifactor.org/AppliedJournals.aspx)

Indexed in Polish Scholarly Bibliography (PBN) (PBN Polska Bibliografia Naukowa) (https://pbn.nauka.gov.pl/journals/36616)

is a portal of the Polish Ministry of Science and Higher Education, collecting information on publications of Polish scientists and on Polish and foreign scholarly journals. Polish Scholarly Bibliograhpy is a part of POL-on - System of Information on Higher Education. It is operated by the Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw.

Indexed in Russian Sciences Index Российский индекс научного цитирования (РИНЦ) http://elibrary.ru/contents.asp?titleid=37467

Indexed in Arianta Polish scientific and professional electronic journals Aneta Drabek i Arkadiusz Pulikowski