Autophagy: A potential novel mechanistic contributor to atrial fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia associated with pronounced morbidity and mortality [ [1] Iwasaki Y.K. Nishida K. Kato T. Nattel S. Atrial fibrillation pathophysiology: implications for management. Circulation. 2011; 124: 2264-2274 Crossref PubMed Scopus (520) Google Scholar ]. Accumulating studies have revealed that atrial remodeling (including electric, structural and autonomic remodeling) is critical to most acquired forms of AF. Among them, atrial fibrosis and apoptosis have been demonstrated playing important roles in AF-promoting pathologies [ [2] Wakili R. Voigt N. Kääb S. Dobrev D. Nattel S. Recent advances in the molecular pathophysiology of atrial fibrillation. J Clin Invest. 2011; 121: 2955-2968 Crossref PubMed Scopus (416) Google Scholar ]. Autophagy, type II programmed cell death, is an intracellular lysosomal degradative process that is essential for survival, differentiation, development, and homeostasis [ [3] Levine B. Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008; 132: 27-42 Abstract Full Text Full Text PDF PubMed Scopus (5433) Google Scholar ]. It was found that AMP-induced protein kinase (AMPK) and beclin-1 dependent pathways play distinct roles in the process of autophagy [ [3] Levine B. Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008; 132: 27-42 Abstract Full Text Full Text PDF PubMed Scopus (5433) Google Scholar ]. Recently, more attention has been paid to the crucial role of autophagy in heart diseases [ [4] Nishida K. Kyoi S. Yamaguchi O. Sadoshima J. Otsu K. The role of autophagy in the heart. Cell Death Differ. 2009; 16: 31-38 Crossref PubMed Scopus (306) Google Scholar ]. For example, Nishida et al. reported that impaired autophagosome clearance contributed to the increased cardiomyocyte death in myocardial ischemia/reperfusion [ [5] Ma X. Liu H. Foyil S.R. et al. Impaired autophagosome clearance contributes to cardiomyocyte death in ischemia/reperfusion injury. Circulation. 2012; 125: 3170-3181 Crossref PubMed Scopus (351) Google Scholar ]. Recently, a couple of studies hinted a close relationship between autophagy and AF in patients developing postoperative AF after coronary artery bypass surgery or mitral regurgitation [ 6 Garcia L. Verdejo H.E. Kuzmicic J. et al. Impaired cardiac autophagy in patients developing postoperative atrial fibrillation. J Thorac Cardiovasc Surg. 2012; 143: 451-459 Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar , 7 Chen M.C. Chang J.P. Wang Y.H. Liu W.H. Ho W.C. Chang H.W. Autophagy as a mechanism for myolysis of cardiomyocytes in mitral regurgitation. Eur J Clin Invest. 2011; 41: 299-307 Crossref PubMed Scopus (24) Google Scholar ]. However, changes of autophagy in most common abnormal electrical activity-induced AF remain unknown. Therefore, our study was performed to explore the alteration of autophagy in atrial myocytes of rapid atrial pacing-induced experimental AF canines and chronic AF patients.