Cookies Notification

We use cookies to improve your website experience. To learn about our use of cookies and how you can manage your cookie settings, please see our Cookie Policy.
×

Regulatory role of cardiomyocyte metabolism via AMPK activation in modulating atrial structural, contractile, and electrical properties following atrial fibrillation

Publication: Canadian Journal of Physiology and Pharmacology
13 October 2020

Abstract

The number of patients diagnosed with atrial fibrillation (AF) has been rising due to increased incidence, enhanced detection methods, and greater survival rates following diagnosis. Due to this increase, AF is now the most commonly diagnosed arrhythmia in clinical practice. AF is characterized by irregular, high-frequency contractions of atrial myocytes that lead to turbulent blood flow and the potential for thrombus formation, stroke, or heart failure. These high-frequency contractions of the atrial myocytes cause an imbalance between metabolic supply and demand. Although advances have been made in understanding the pathophysiology of AF, the etiology and underlying pathogenic mechanism remain unknown. However, recent evidence suggests that cardiomyocyte metabolism involving 5′ AMP-activated protein kinase (AMPK) activation is altered in patients with AF. Here, we critically reviewed the current understanding of AMPK activation in AF and how it could affect structural, contractile, and electrophysiological cellular properties in the pathogenesis of AF.

Résumé

Le nombre de patient ayant reçu un diagnostic de fibrillation atriale (FA) est à la hausse en raison d’une augmentation de son incidence, de l’amélioration des modes de détection et d’une augmentation des taux de survie à la suite du diagnostic. En raison de cette augmentation, la FA est maintenant l’arythmie la plus fréquemment diagnostiquée en pratique clinique. La FA se caractérise par des contractions irrégulières à fréquence élevée des myocytes atriaux, menant à un flux sanguin turbulent et à la possibilité de la formation d’un thrombus ainsi que de l’apparition d’un AVC et d’une insuffisance cardiaque. Ces contractions à haute fréquence des myocytes atriaux entraînent un déséquilibre entre l’apport et la demande métaboliques. Bien que des avancées aient été réalisées dans la compréhension de la physiopathologie de la FA, son étiologie et les modes d’action pathogènes sous-jacents demeurent inconnus. Cependant, des données récentes laissent entrevoir que le métabolisme des cardiomyocytes mettant en jeu l’activation de la protéine kinase activée par le 5′ AMP (AMPK) serait altéré chez les patients atteints de FA. Nous présentons ici une synthèse critique de la littérature portant sur la compréhension actuelle du rôle de l’activation de l’AMPK dans la FA, et sur comment celle-là pourrait affecter les propriétés structurelles, contractiles et électrophysiologiques des cellules dans la pathogenèse de la FA. [Traduit par la Rédaction]

Get full access to this article

View all available purchase options and get full access to this article.

References

Alaynick W.A., Kondo R.P., Xie W., He W., Dufour C.R., Downes M., et al. 2007. ERRgamma directs and maintains the transition to oxidative metabolism in the postnatal heart. Cell Metab. 6(1): 13–24.
Allessie M.A., Boyden P.A., Camm A.J., Kléber A.G., Lab M.J., Legato M.J., et al. 2001. Pathophysiology and prevention of atrial fibrillation. Circulation, 103(5): 769–777.
Arad M., Moskowitz I.P., Patel V.V., Ahmad F., Perez-Atayde A.R., Sawyer D.B., et al. 2003. Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff-Parkinson-White syndrome in glycogen storage cardiomyopathy. Circulation, 107(22): 2850–2856.
Arad M., Seidman C.E., and Seidman J.G. 2007. AMP-activated protein kinase in the heart: role during health and disease. Circ. Res. 100(4): 474–488.
Beauloye C., Bertrand L., Horman S., and Hue L. 2011. AMPK activation, a preventive therapeutic target in the transition from cardiac injury to heart failure. Cardiovasc. Res. 90(2): 224–233.
Chugh S.S., Havmoeller R., Narayanan K., Singh D., Rienstra M., Benjamin E.J., et al. 2014. Worldwide epidemiology of atrial fibrillation: a global burden of disease 2010 study. Circulation, 129(8): 837–847.
Colilla S., Crow A., Petkun W., Singer D.E., Simon T., and Liu X. 2013. Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population. The Am. J. ogy. 112(8): 1142–1147.
Disch D.L. 1994. Managing chronic atrial fibrillation: a Markov decision analysis comparing warfarin, quinidine, and low-dose amiodarone. Ann. Intern. Med. 120(6): 449.
Dyck J.R.B. and Lopaschuk G.D. 2006. AMPK alterations in cardiac physiology and pathology: enemy or ally? J. Physiol. 574(Pt. 1): 95–112.
Frederich M. and Balschi J.A. 2002. The relationship between AMP-activated protein kinase activity and AMP concentration in the isolated perfused rat heart. J. Biol. Chem. 277(3): 1928–1932.
Frost L., Vestergaard P., Mosekilde L., and Mortensen L.S. 2005. Trends in incidence and mortality in the hospital diagnosis of atrial fibrillation or flutter in Denmark, 1980–1999. Int. J. Cardiol. 103(1): 78–84.
Galuska D., Zierath J., Thörne A., Sonnenfeld T., and Wallberg-Henriksson H. 1991. Metformin increases insulin-stimulated glucose transport in insulin-resistant human skeletal muscle. Diabetes Metab. 17(1 Pt. 2): 159–163.
Ghezelbash S., Molina C.E., and Dobrev D. 2015. Altered atrial metabolism: an underappreciated contributor to the initiation and progression of atrial fibrillation. J. Am. Heart Assoc. 4(3): e001808.
Harada M., Nattel S.N., and Nattel S. 2012. AMP-activated protein kinase: potential role in cardiac electrophysiology and arrhythmias. Circ. Arrhythm. Electrophysiol. 5(4): 860–867.
Harada M., Tadevosyan A., Qi X., Xiao J., Liu T., Voigt N., et al. 2015. Atrial fibrillation activates AMP-dependent protein kinase and its regulation of cellular calcium handling: potential role in metabolic adaptation and prevention of progression. J. Am. Coll. Cardiol. 66(1): 47–58.
Harada M., Melka J., Sobue Y., and Nattel S. 2017. Metabolic considerations in atrial fibrillation - mechanistic insights and therapeutic opportunities. Circ. J. 81(12): 1749–1757.
Hardie D.G., Hawley S.A., and Scott J.W. 2006. AMP-activated protein kinase–development of the energy sensor concept. J. Physiol. 574(Pt. 1): 7–15.
Ikeda Y., Sato K., Pimentel D.R., Sam F., Shaw R.J., Dyck J.R.B., and Walsh K. 2009. Cardiac-specific deletion of LKB1 leads to hypertrophy and dysfunction. J. Biol. Chem. 284(51): 35839–35849.
Kim J., Yang G., Kim Y., Kim J., and Ha J. 2016. AMPK activators: mechanisms of action and physiological activities. Exp. Mol. Med. 48: e224.
Kim M.H., Johnston S.S., Chu B.-C., Dalal M.R., and Schulman K.L. 2011. Estimation of total incremental health care costs in patients with atrial fibrillation in the United States. Circ. Cardiovasc. Qual. Outcomes, 4(3): 313–320.
Kolwicz S.C., Purohit S., and Tian R. 2013. Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes. Circ. Res. 113(5): 603–616.
Krijthe B.P., Kunst A., Benjamin E.J., Lip G.Y.H., Franco O.H., Hofman A., et al. 2013. Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060. Eur. Heart J. 34(35): 2746–2751.
Lee W.C., Lamas G.A., Balu S., Spalding J., Wang Q., and Pashos C.L. 2008. Direct treatment cost of atrial fibrillation in the elderly American population: a Medicare perspective. J. Med. Econ. 11(2): 281–298.
Lehman J.J., Barger P.M., Kovacs A., Saffitz J.E., Medeiros D.M., and Kelly D.P. 2000. Peroxisome proliferator–activated receptor γ coactivator-1 promotes cardiac mitochondrial biogenesis. J. Clin. Invest. 106(7): 847–856.
Lenski M., Schleider G., Kohlhaas M., Adrian L., Adam O., Tian Q., et al. 2015. Arrhythmia causes lipid accumulation and reduced glucose uptake. Basic Res. Cardiol. 110(4): 40.
Lip G.Y., Metcalfe M.J., and Rae A.P. 1993. Management of paroxysmal atrial fibrillation. Q. J. Med. 86(8): 467–472.
Liu Y., Bai F., Liu N., Zhang B., Qin F., Tu T., et al. 2020. Metformin improves lipid metabolism and reverses the Warburg effect in a canine model of chronic atrial fibrillation. BMC Cardiovasc. Disord. 20: 50.
Michalik L., Desvergne B., Dreyer C., Gavillet M., Laurini R.N., and Wahli W. 2002. PPAR expression and function during vertebrate development. Int. J. Dev. Biol. 46(1): 105–114.
Miyasaka Y., Barnes M.E., Gersh B.J., Cha S.S., Bailey K.R., Abhayaratna W.P., et al. 2006. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation, 114(2): 119–125.
Nattel S., Guasch E., Savelieva I., Cosio F.G., Valverde I., Halperin J.L., et al. 2014. Early management of atrial fibrillation to prevent cardiovascular complications. Eur. Heart J. 35(22): 1448–1456.
Ozcan C., Battaglia E., Young R., and Suzuki G. 2015. LKB1 knockout mouse develops spontaneous atrial fibrillation and provides mechanistic insights into human disease process. J Am. Heart Assoc. 4(3): e001733.
Ozcan C., Li Z., Kim G., Jeevanandam V., and Uriel N. 2019. Molecular mechanism of the association between atrial fibrillation and heart failure includes energy metabolic dysregulation due to mitochondrial dysfunction. J. Card. Fail. 25(11): 911–920.
Piccini J.P., Hammill B.G., Sinner M.F., Jensen P.N., Hernandez A.F., Heckbert S.R., et al. 2012. Incidence and prevalence of atrial fibrillation and associated mortality among medicare beneficiaries: 1993–2007. Circ. Cardiovasc. Qual. Outcomes, 5(1): 85–93.
Raney M.A. and Turcotte L.P. 2008. Evidence for the involvement of CaMKII and AMPK in Ca2+-dependent signaling pathways regulating FA uptake and oxidation in contracting rodent muscle. J. Appl. Physiol. (1985), 104(5): 1366–1373.
Semenza G.L. 2011. Hypoxia-inducible factor 1: Regulator of mitochondrial metabolism and mediator of ischemic preconditioning. Biochim. Biophys. Acta, 1813(7): 1263–1268.
Stewart S., Murphy N., Walker A., McGuire A., and McMurray J.J.V. 2004. Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart, 90(3): 286–292.
Sugden M.C. and Holness M.J. 2003. Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs. Am. J. Physiol. Endocrinol. Metab. 284(5): E855–E862.
Towler M.C. and Hardie D.G. 2007. AMP-activated protein kinase in metabolic control and insulin signaling. Circ. Res. 100(3): 328–341.
Viollet B., Horman S., Leclerc J., Lantier L., Foretz M., Billaud M., et al. 2010. AMPK inhibition in health and disease. Crit. Rev. Biochem. Mol. Biol. 45(4): 276–295.
Wakili R., Voigt N., Kääb S., Dobrev D., and Nattel S. 2011. Recent advances in the molecular pathophysiology of atrial fibrillation. J. Clin. Invest. 121(8): 2955–2968.
Wann L.S., January C.T., Ellenbogen K.A., Lowe J.E., Estes N.A.M., Page R.L., et al. 2011. 2011 ACCF/AHA/HRS Focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation, 123(1): 1144–1123.
Witters L.A. 2001. The blooming of the French lilac. J. Clin. Invest. 108(8): 1105–1107.
Wood A.J.J. and Pritchett E.L.C. 1992. Management of atrial fibrillation. N. Eng. J. Med. 326(19): 1264–1271.
Young L.H. 2008. AMP-activated protein kinase conducts the ischemic stress response orchestra. Circulation, 117(6): 832–840.

Information & Authors

Information

Published In

cover image Canadian Journal of Physiology and Pharmacology
Canadian Journal of Physiology and Pharmacology
Volume 99Number 1January 2021
Pages: 36 - 41

History

Received: 14 June 2020
Accepted: 4 October 2020
Accepted manuscript online: 13 October 2020
Version of record online: 13 October 2020

Notes

This paper is part of a special issue of selected papers from the Joint North American/European IACS 2019.

Permissions

Request permissions for this article.

Key Words

  1. atrial fibrillation
  2. cardiomyocyte metabolism
  3. cardiomyocyte
  4. cardiac metabolism
  5. arrhythmias
  6. AMPK

Mots-clés

  1. fibrillation atriale
  2. métabolisme des cardiomyocytes
  3. cardiomyocytes
  4. métabolisme cardiaque
  5. arythmies
  6. AMPK

Authors

Affiliations

Sean M. Brown
Creighton University School of Medicine, Omaha, NE 68178, USA.
Nicholas K. Larsen
Creighton University School of Medicine, Omaha, NE 68178, USA.
Finosh G. Thankam
Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA.
Devendra K. Agrawal [email protected]
Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA.

Notes

Devendra K. Agrawal serves as an Associate Editor; peer review and editorial decisions regarding this manuscript were handled by Dragan Djuric.
Copyright remains with the author(s) or their institution(s). Permission for reuse (free in most cases) can be obtained from copyright.com.

Metrics & Citations

Metrics

Other Metrics

Citations

Cite As

Export Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

Cited by

1. Hygrothermal stress increases malignant arrhythmias susceptibility by inhibiting the LKB1-AMPK-Cx43 pathway
2. The Management of Postoperative Atrial Fibrillation (POAF): A Systematic Review
3. Cannabinoid receptor agonist attenuates angiotensin II–induced enlargement and mitochondrial dysfunction in rat atrial cardiomyocytes
4. Intermittent fasting attenuates obesity-related atrial fibrillation via SIRT3-mediated insulin resistance mitigation
5. Protective effects of metformin in various cardiovascular diseases: Clinical evidence and AMPK ‐dependent mechanisms

View Options

Get Access

Login options

Check if you access through your login credentials or your institution to get full access on this article.

Subscribe

Click on the button below to subscribe to Canadian Journal of Physiology and Pharmacology

Purchase options

Purchase this article to get full access to it.

Restore your content access

Enter your email address to restore your content access:

Note: This functionality works only for purchases done as a guest. If you already have an account, log in to access the content to which you are entitled.

View options

PDF

View PDF

Full Text

View Full Text

Media

Media

Other

Tables

Share Options

Share

Share the article link

Share on social media