Troponin I Isoform Expression in Human and Experimental Atrial Fibrillation

Abstract

Background-Atrial fibrillation (AF) is accompanied by re-expression of fetal genes and activation of proteolytic enzymes. In this study both aspects were addressed with respect to troponin I (TnI) isoform expression. Methods and Results-Western blotting and real-time reverse transcription-polymerase chain reaction were used to study TnI isoform expression in patients with paroxysmal or chronic AF and in goats after 1, 2, 4, 8, and 16 weeks of AF. In addition to cardiac TnI (cTnI), low expression of slow-twitch skeletal TnI (ssTnI) protein was found in 60% of patients in sinus rhythm or paroxysmal AF and in 8% of patients with chronic AF. In adult goat atrium, ssTnI protein expression was undetectable. Calcium-dependent degradation of cTnI protein was found in 1 or 2 of 6 animals after 1 to 4 weeks of AF. Although always low, ssTnI mRNA levels were significantly higher in patients who expressed ssTnI protein than in those who did not. Relative ssTnI mRNA expression was significantly lower in patients with paroxysmal AF and chronic AF than in those in sinus rhythm. In goats there was a tendency toward higher relative levels of ssTnI at the onset of AF followed by a normalization when AF had become sustained. Conclusions-Atrial re-expression of ssTnI during paroxysmal AF in patients and during the first 2 weeks of pacing-induced AF in goats does not seem to be part of the process of AF-associated cardiomyocyte dedifferentiation but seems to result from transient cardiomyocyte stress at the onset of AF.

Effects of Chronic Atrial Fibrillation on Active and Passive Force Generation in Human Atrial Myofibrils

“…11 The predominant cTnI degradation product (cTnI 1 to 192 ) has been shown to significantly increase Ca 2ϩ sensitivity of human cardiac myofibrils. 14 However, in the present and previous studies 9,31 no changes in troponin content were observed and cTnI degradation products were undetectable in atrial samples from cAF patients.…”

“…30 Although re-expression of ssTnI has been described in the early stages of AF in human atria and in a goat model of the disease, ssTnI was undetectable in atrial samples from patients with cAF. 31 A relation has been found in human atria between cAF and the activity of calpain-1, 32 a protease involved in degradation of contractile proteins, 33 including cTn. 34 Degradation of cTn by calpain has been reported to occur in both human cAF and a cell model for tachypacinginduced remodeling.…”

Calmodulin kinase II–mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice

“…Using singlechannel bilayer recordings, Vest et al demonstrated an increased open probability of RyR2 channels isolated from dogs in persistent AF (4). This finding and the observation that RyR2 expression levels are unaltered or decreased in patients with chronic AF (33)(34)(35)(36) suggest that remodeling of the RyR2 macromolecular complex may underlie the defective channel function in chronic AF.…”

Atrial Fibrillation in Children

“…There has been a recent focus on hormonal control of atrial electrophysiology, including genes controlling atrial natriuretic peptide levels and mineralocorticoid receptor expression, in patients with atrial fibrillation (Hodgson-Zingman et al, 2008;Roberts & Gollob, 2010;Tsai et al, 2010). Re-expression of dormant fetal genes may be one mechanism associated with the development of atrial fibrillation in adults, as was demonstrated by the appearance of the fetal ssTnI isoform of troponin in patients with atrial fibrillation (Thijssen et al, 2004). These changes could be primary causes of atrial fibrillation or may represent secondary changes related to other changes in myocardial metabolism, function or distension.…”