TY - JOUR
T1 - Troponin I isoform expression in human and experimental atrial fibrillation
AU - Thijssen, Victor L J L
AU - Ausma, Jannie
AU - Gorza, Luisa
AU - van der Velden, Huub M W
AU - Allessie, Maurits A
AU - Van Gelder, Isabelle C
AU - Borgers, Marcel
AU - van Eys, Guillaume J J M
PY - 2004/8/17
Y1 - 2004/8/17
N2 - 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.
AB - 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.
KW - Acute Disease
KW - Animals
KW - Atrial Fibrillation/genetics
KW - Blotting, Western
KW - Calcium/physiology
KW - Chronic Disease
KW - Fetal Heart/metabolism
KW - Gene Expression Regulation
KW - Goats/embryology
KW - Humans
KW - Mitral Valve Insufficiency/genetics
KW - Models, Animal
KW - Models, Genetic
KW - Myocytes, Cardiac/metabolism
KW - Phosphorylation
KW - Protein Isoforms/biosynthesis
KW - Protein Processing, Post-Translational
KW - RNA, Messenger/biosynthesis
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Species Specificity
KW - Troponin I/biosynthesis
U2 - 10.1161/01.CIR.0000138849.03311.C6
DO - 10.1161/01.CIR.0000138849.03311.C6
M3 - Article
C2 - 15289369
VL - 110
SP - 770
EP - 775
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 7
ER -