rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2016-12-5-582-589rpcardio-1340Research ArticlePOINT OF VIEWТОЧКА ЗРЕНИЯPathogenic Mechanisms of Atrial Fibrillation in ObesityПатогенетические механизмы развития фибрилляции предсердий при ожиренииДрапкинаО. М.DrapkinaO. M.

д.м.н., профессор, первый заместитель директора по научной и лечебной работе ГНИЦ ПМ

MD, PhD, Professor, Deputy Director for Research and Clinical Work, State Research Center for Preventive Medicine

drapkina@bk.ruНиколаеваМ. В.NikolaevaM. V.

студентка 5 курса Первого МГМУ им. И.М. Сеченова

5th Year Student, I.M. Sechenov First Moscow State Medical University

Государственный научно-исследовательский центр профилактической медицины Россия, 101990, Москва, Петроверигский пер., 10, стр 3РоссияState Research Center for Preventive Medicine. Petroverigsky per. 10, Moscow, 101990 RussiaRussian FederationПервый московский государственный медицинский университет имени И.М. Сеченова Россия, 119991, Москва, ул. Трубецкая, 8 стр. 2РоссияI.M. Sechenov First Moscow State Medical University. Trubetskaya ul. 8-2, Moscow, 119991 RussiaRussian Federation201606112016125582589Copyright © Drapkina O.M., Nikolaeva M.V., 20162016Драпкина О.М., Николаева М.В.Drapkina O.M., Nikolaeva M.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/1340

Atrial fibrillation (AF) is one of the most common arrhythmias. It reduces quality of life and its duration due to thromboembolic complications. Obesity contributes to the structural and electrical remodeling of atrial myocardium. This leads to occurrence of ectopic foci in the mouths of the pulmonary veins and the disruption of normal electrical conduction in the atria. Systemic inflammation, myocardial fibrosis, cardiomyocyte overload by Na+ and Ca2+ ions, accumulation in the cells of unoxidized metabolic products, imbalance of the autonomic regulation are considered as the main mechanisms of arrhythmogenic substrate formation. Hypertension, insulin resistance, and obstructive sleep apnea, associated with obesity, increase the risk of development and progression of the arrhythmia. Study of pathogenetic mechanisms of AF in obesity is necessary to develop new strategies for its prevention and the creation of more effective methods of treatment of these patients.

Фибрилляция предсердий (ФП) является одной из наиболее распространенных аритмий. Ее появление приводит к снижению качества жизни и уменьшению ее продолжительности за счет тромбоэмболических осложнений. Ожирение способствует структурному и электрическому ремоделированию миокарда предсердий, что приводит к возникновению эктопических фокусов в устьях легочных вен и нарушению нормального электрического проведения по предсердиям. К основным механизмам формирования аритмогенного субстрата относят системное воспаление, фиброз миокарда, перегрузку кардиомиоцитов ионами Na+ и Са2+, накопление в клетках недоокисленных продуктов метаболизма, дисбаланс вегетативной регуляции. Ассоциированные с ожирением артериальная гипертензия, инсулинорезистентность и синдром обструктивного апноэ сна повышают риск возникновения и прогрессирования аритмии. Исследование патогенетических механизмов возникновения ФП при ожирении необходимо для разработки новых стратегий ее профилактики и создания более эффективных методов лечения у данной группы пациентов.

фибрилляция предсердийожирениевоспалениефиброзatrial fibrillationobesityinflammationfibrosisReferencesPoirer P, Eckel R. Cardiovascular consequences of obesity. Drug Discovery Today: Therapeutic strategies. 2008; 5: 45-51. doi: 10.1016/j.ddstr.2008.05.005.Poirer P, Eckel R. Cardiovascular consequences of obesity. Drug Discovery Today: Therapeutic strategies. 2008; 5: 45-51. doi: 10.1016/j.ddstr.2008.05.005.Abed HS, Wittert GA. Obesity and atrial fibrillation. Obes Rev. 2013 Nov;14(11):929-38. doi: 10.1111/obr.12056.Abed HS, Wittert GA. Obesity and atrial fibrillation. Obes Rev. 2013 Nov;14(11):929-38. doi: 10.1111/obr.12056.McCully B, Hasan W, Streif C. Sypmathetic cardiac hyperinnervation and atrial autonomic imbalance in diet-induced obesity promote cardiac arrhythmias. Am J Heart Circ Physiol. 2013;305(10):1530- 7. doi: 10.1152/ajpheart.00196.2013.McCully B, Hasan W, Streif C. Sypmathetic cardiac hyperinnervation and atrial autonomic imbalance in diet-induced obesity promote cardiac arrhythmias. Am J Heart Circ Physiol. 2013;305(10):1530- 7. doi: 10.1152/ajpheart.00196.2013.Goudis CA, Korantzopoulos P, Ntalas IV, et al. Obesity and atrial fibrillation: A comprehensive review of the pathophysiological mechanisms and links. J Cardiol. 2015;66(5):361-9. doi: 10.1016/j.jjcc.2015.04.002.Goudis CA, Korantzopoulos P, Ntalas IV, et al. Obesity and atrial fibrillation: A comprehensive review of the pathophysiological mechanisms and links. J Cardiol. 2015;66(5):361-9. doi: 10.1016/j.jjcc.2015.04.002.Kotsis V, Stabouli S, Papakatsika S, et al. Mechanisms of obesity-induced hypertension. Hypertens Res. 2010;33(5):386-93. doi: 10.1038/hr.2010.9.Kotsis V, Stabouli S, Papakatsika S, et al. Mechanisms of obesity-induced hypertension. Hypertens Res. 2010;33(5):386-93. doi: 10.1038/hr.2010.9.Lin C, Pan C. Regulatory mechanisms of atrial fibrotic remodeling in atrial fibrillation. Cellular and Molecular Life Sciences. 2008;65:1489-508. doi: 10.1007/s00018-008-7408-8.Lin C, Pan C. Regulatory mechanisms of atrial fibrotic remodeling in atrial fibrillation. Cellular and Molecular Life Sciences. 2008;65:1489-508. doi: 10.1007/s00018-008-7408-8.Oleinik OA, Samoilova YG, Vorozhtsova IN, et al. Clinical and metabolic and molecular genetic mechanisms of cardiovascular complications of obesity. Sibirskiy Meditsinskiy Zhurnal. 2011; 26 (4): 16-22. (In Russian) [Олейник О.А., Самойлова Ю.Г., Ворожцова И.Н., и др. Клинико-метаболические и молекулярно-генетические механизмы формирования кардиоваскулярных осложнений при ожирении. Сибирский Медицинский Журнал. 2011;26(4):16-22].Oleinik OA, Samoilova YG, Vorozhtsova IN, et al. Clinical and metabolic and molecular genetic mechanisms of cardiovascular complications of obesity. Sibirskiy Meditsinskiy Zhurnal. 2011; 26 (4): 16-22. (In Russian) [Олейник О.А., Самойлова Ю.Г., Ворожцова И.Н., и др. Клинико-метаболические и молекулярно-генетические механизмы формирования кардиоваскулярных осложнений при ожирении. Сибирский Медицинский Журнал. 2011;26(4):16-22].Fantuzzi G. Health versus disease as the catalyst for biomedical research: the science of adipokines as a case in point. Front Endocrinol. 2014;5(136):1-3. doi:10.3389/fendo.2014.00136.Fantuzzi G. Health versus disease as the catalyst for biomedical research: the science of adipokines as a case in point. Front Endocrinol. 2014;5(136):1-3. doi:10.3389/fendo.2014.00136.Goudis C, Korantzopoulos P, Ntalas I. Diabetes mellitus and atrial fibrillation: Pathophysiological mechanisms and potential upstream therapies. International Journal of Cardiology. 2015;184:617-22. doi: 10.1016/j.ijcard.2015.03.052.Goudis C, Korantzopoulos P, Ntalas I. Diabetes mellitus and atrial fibrillation: Pathophysiological mechanisms and potential upstream therapies. International Journal of Cardiology. 2015;184:617-22. doi: 10.1016/j.ijcard.2015.03.052.Shkadova MG, Klaritskaya IL, Grigorenko EI. Obesity as a cause of obstructive sleep apnea and GERD. Krymskiy Terapevticheskiy Zhurnal. 2013; (2): 161-6. (In Russian) [Шкадова М.Г., Кларитская И.Л., Григоренко Е.И. Ожирение как причина синдрома обструктивного апноэ сна и ГЭРБ. Крымский Терапевтический Журнал. 2013;(2):161-6].Shkadova MG, Klaritskaya IL, Grigorenko EI. Obesity as a cause of obstructive sleep apnea and GERD. Krymskiy Terapevticheskiy Zhurnal. 2013; (2): 161-6. (In Russian) [Шкадова М.Г., Кларитская И.Л., Григоренко Е.И. Ожирение как причина синдрома обструктивного апноэ сна и ГЭРБ. Крымский Терапевтический Журнал. 2013;(2):161-6].Shamsheva D.Sh. Obstructive sleep apnea syndrome: state of the art. Lechebnoe Delo. 2014; (1): 1-13. (In Russian) [Шамшева Д.Ш. Синдром обструктивного апноэ сна: современное состояние проблемы. Лечебное Дело. 2014;(1):1-13].Shamsheva D.Sh. Obstructive sleep apnea syndrome: state of the art. Lechebnoe Delo. 2014; (1): 1-13. (In Russian) [Шамшева Д.Ш. Синдром обструктивного апноэ сна: современное состояние проблемы. Лечебное Дело. 2014;(1):1-13].Yagmur J, Yetkin O, Cansel M. Assessment of atrial electromechanical delay and influential factors in patients with obstructive sleep apnea. Sleep Breath. 2012;16(1):83-8. doi: 10.1007/s11325-010- 0477-6.Yagmur J, Yetkin O, Cansel M. Assessment of atrial electromechanical delay and influential factors in patients with obstructive sleep apnea. Sleep Breath. 2012;16(1):83-8. doi: 10.1007/s11325-010- 0477-6.Khawaja O, Bartz T, Ix JH, et al. Plasma free fatty acids and risk of atrial fibrillation (from the Cardiovascular Health Study). Am J Cardiol. 2012;110(2):212-6. doi: 10.1016/j.a mjcard.2012.03.010.Khawaja O, Bartz T, Ix JH, et al. Plasma free fatty acids and risk of atrial fibrillation (from the Cardiovascular Health Study). Am J Cardiol. 2012;110(2):212-6. doi: 10.1016/j.a mjcard.2012.03.010.Gizurarson S, Stahlman M, Omerovic E, et al. Atrial fibrillation in patients admitted to coronary care unit in western Sweden – focus on obesity and lipotoxicity. J Electrocardiol. 2015 Sep-Oct;48(5):853- 60. doi: 10.1016/j.jelectrocard.2014.12.010.Gizurarson S, Stahlman M, Omerovic E, et al. Atrial fibrillation in patients admitted to coronary care unit in western Sweden – focus on obesity and lipotoxicity. J Electrocardiol. 2015 Sep-Oct;48(5):853- 60. doi: 10.1016/j.jelectrocard.2014.12.010.Chubrieva SY, Glukhov NV, Zaichik AM. Adipose tissue as an endocrine regulator. Vestnik Sankt-Peterburgskogo Universiteta. 2008; 11 (1): 32-42. (In Russian) [Чубриева С.Ю., Глухов Н.В., Зайчик А.М. Жировая ткань как эндокринный регулятор. Вестник Санкт- Петербургского Университета. 2008;11(1):32-42].Chubrieva SY, Glukhov NV, Zaichik AM. Adipose tissue as an endocrine regulator. Vestnik Sankt-Peterburgskogo Universiteta. 2008; 11 (1): 32-42. (In Russian) [Чубриева С.Ю., Глухов Н.В., Зайчик А.М. Жировая ткань как эндокринный регулятор. Вестник Санкт- Петербургского Университета. 2008;11(1):32-42].Gil A, María Aguilera C, Gil-Campos M, Cañete R. Altered signaling and gene expression associated with the immune system and inflammatory response in obesity. Br J Nutr. 2007 Oct;98 Suppl 1:S121-6. doi: 10.1017/S0007114507838050.Gil A, María Aguilera C, Gil-Campos M, Cañete R. Altered signaling and gene expression associated with the immune system and inflammatory response in obesity. Br J Nutr. 2007 Oct;98 Suppl 1:S121-6. doi: 10.1017/S0007114507838050.Schwartz B. Inflammation of adipose tissue (part 1). Morphological and functional manifestations. Problemy Endokrinologii. 2009; 55 (4): 44-9. (In Russian) [Шварц В. Воспаление жировой ткани (часть 1). Морфологические и функциональные проявления. Проблемы Эндокринологии. 2009;55(4):44-9].Schwartz B. Inflammation of adipose tissue (part 1). Morphological and functional manifestations. Problemy Endokrinologii. 2009; 55 (4): 44-9. (In Russian) [Шварц В. Воспаление жировой ткани (часть 1). Морфологические и функциональные проявления. Проблемы Эндокринологии. 2009;55(4):44-9].Adiarto S, Emoto N, Iwasa N. Obesity-indused upregulation of myocardial endothelin-1 expression is mediated by leptin. Biochemical and Biophysical Research Communication. 2007;353:623-7. doi:10.1016/j.bbrc.2006.12.066.Adiarto S, Emoto N, Iwasa N. Obesity-indused upregulation of myocardial endothelin-1 expression is mediated by leptin. Biochemical and Biophysical Research Communication. 2007;353:623-7. doi:10.1016/j.bbrc.2006.12.066.Fukui A, Takanashi N, Nakada C. Role of leptin signaling in the pathogenesis of angiotensis II-mediated atrial fibrosis and fibrillation. Circ Arrhythm Electrophysiol. 2013;6(2):402-9. doi: 10.1161/CIRCEP. 111.000104.Fukui A, Takanashi N, Nakada C. Role of leptin signaling in the pathogenesis of angiotensis II-mediated atrial fibrosis and fibrillation. Circ Arrhythm Electrophysiol. 2013;6(2):402-9. doi: 10.1161/CIRCEP. 111.000104.Lin Y, Chen Y, Huang J. Leptin modulates electrophysiological characteristics and isoproterenol-induced arrhythmogenesis in atrial myocytes. J Biomed Sci. 2013;20:94. doi: 10.1186/1423-0127-20-94.Lin Y, Chen Y, Huang J. Leptin modulates electrophysiological characteristics and isoproterenol-induced arrhythmogenesis in atrial myocytes. J Biomed Sci. 2013;20:94. doi: 10.1186/1423-0127-20-94.Jacobsen M, Junker Mentzel C, Olesen A, et al. Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity. J Diabetes Res. 2016;2016:8539057. doi: 10.1155/2016/8539057.Jacobsen M, Junker Mentzel C, Olesen A, et al. Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity. J Diabetes Res. 2016;2016:8539057. doi: 10.1155/2016/8539057.Hatem S, Redheuil A, Gandjbakhch A. Cardiac adipose tissue and atrial fibrillation: the perils of adiposity. Cardiovasc Res. 2016;109(4):502-9. doi: 10.1093/cvr/cvw001.Hatem S, Redheuil A, Gandjbakhch A. Cardiac adipose tissue and atrial fibrillation: the perils of adiposity. Cardiovasc Res. 2016;109(4):502-9. doi: 10.1093/cvr/cvw001.Wong C, Ganesan A, Selvanayagam J. Epicardial fat and atrial fibrillation: current evidence, potential mechanisms, clinical implications, and future direction. Eur Heart J. 2016 Mar 1. pii: ehw045. doi:10.1093/eurheart/ehw045.Wong C, Ganesan A, Selvanayagam J. Epicardial fat and atrial fibrillation: current evidence, potential mechanisms, clinical implications, and future direction. Eur Heart J. 2016 Mar 1. pii: ehw045. doi:10.1093/eurheart/ehw045.Gaborit B, Venteclef, Ancel P. et al. Human Epicardial adipose tissue has a specific transcriptomic signature depending on its anatomical peri-atrial, peri-ventricular, or peri- coronary location. Cardiovasc Res. 2015;108:62-73. doi: 10.1093/cvr/cvv208.Gaborit B, Venteclef, Ancel P. et al. Human Epicardial adipose tissue has a specific transcriptomic signature depending on its anatomical peri-atrial, peri-ventricular, or peri- coronary location. Cardiovasc Res. 2015;108:62-73. doi: 10.1093/cvr/cvv208.Lin Y, Chen Y, Chen S. Potential atrial arrhythmogenicity of adipocytes: Implications for the genesis of atrial fibrillation. Med Hypotheses. 2010;74(6):1026-9. doi: 10.1016/j.mehy.2010.01.004.Lin Y, Chen Y, Chen S. Potential atrial arrhythmogenicity of adipocytes: Implications for the genesis of atrial fibrillation. Med Hypotheses. 2010;74(6):1026-9. doi: 10.1016/j.mehy.2010.01.004.Chilukoti R, Giese A, Malenke W, et al. Atrial fibrillation and rapid acute pacing regulate adipocyte/adipositas-related gene expression in the atria. International Journal of Cardiology. 2014;187:604-13. doi: 10.1016/j.ijcard.2015.03.072.Chilukoti R, Giese A, Malenke W, et al. Atrial fibrillation and rapid acute pacing regulate adipocyte/adipositas-related gene expression in the atria. International Journal of Cardiology. 2014;187:604-13. doi: 10.1016/j.ijcard.2015.03.072.Stavrakis S, Nakagawa H, Po SS, et al. The role of the Autonomic Ganglia in Atrial Fibrillation. JACC Clin Electrophysiol. 2015;1(1-2):1-13. doi: 10.1016/j.jacep.2015.01.005Stavrakis S, Nakagawa H, Po SS, et al. The role of the Autonomic Ganglia in Atrial Fibrillation. JACC Clin Electrophysiol. 2015;1(1-2):1-13. doi: 10.1016/j.jacep.2015.01.005Guauque-Olarte S, Gaudreault N, PichéMÈ, et al. The Transkriptome of Human Epicardial, Mediastinal and Subcutaneous Adipose Tissues in Men with Coronary Artery Disease. PLoS One. 2011;6(5):e19908. doi: 10.1371/journal.pone.0019908.Guauque-Olarte S, Gaudreault N, PichéMÈ, et al. The Transkriptome of Human Epicardial, Mediastinal and Subcutaneous Adipose Tissues in Men with Coronary Artery Disease. PLoS One. 2011;6(5):e19908. doi: 10.1371/journal.pone.0019908.Yang W, Xu L, Zhang H. Association of CETP and CRP gene polymorphisms with non-valvular Atrial Fibrillation in Chinese Han population. Zhonghua Yi Chuan Xue Za Zhi. 2008; 25: 225-9.Yang W, Xu L, Zhang H. Association of CETP and CRP gene polymorphisms with non-valvular Atrial Fibrillation in Chinese Han population. Zhonghua Yi Chuan Xue Za Zhi. 2008; 25: 225-9.Lim J, Iyer A, Liu L. Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism. FASEB J. 2013;27(12):4757-67. doi: 10.1096/fj.13-232702.Lim J, Iyer A, Liu L. Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism. FASEB J. 2013;27(12):4757-67. doi: 10.1096/fj.13-232702.GalalAzzam HA. Chapter 6. Thrombogenesis in Atrial Fibrillation. In: Liu T, ed. Atrial Fibrillation - Mechanisms and Treatment. InTech; 2013. P.138.GalalAzzam HA. Chapter 6. Thrombogenesis in Atrial Fibrillation. In: Liu T, ed. Atrial Fibrillation - Mechanisms and Treatment. InTech; 2013. P.138.

The authors declare that there are no conflicts of interest present.