DNA repair in TUNEL-positive atrial cardiomyocytes of mitral and tricuspid valve diseases: Potential mechanism for preserving cardiomyocytes

Background: The reported presence of DNA breaks, based on a positive reaction to the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end-labelling (TUNEL) assay, in fibrillating human right atria of cardiac valve disease may suggest apoptotic myocyte death. However, TUNEL positivity may reflect conditions other than cell death. Methods: This study comprised 27 adult patients (14 patients with persistent atrial fibrillation and 13 in sinus rhythm) with significant mitral and tricuspid valve diseases. Atrial tissues were obtained during surgery. Results: Immunohistochemical study demonstrated that 31.1 ± 12.2% of the myocytes had TUNEL-positive nuclei in the fibrillating right atria whereas 37.4 ± 23.2% of the myocytes had TUNEL-positive nuclei in the right atrial myocardium in sinus rhythm (p = 0.505). However, most nuclei of TUNEL-positive myocytes in the right atria also expressed proliferating cell nuclear antigen (PCNA), an indicator of DNA replication and repair but never Ki-67, a replication-associated antigen (TUNEL⁺/PCNA⁺ vs. TUNEL⁺/PCNA^-, 30.5 ± 10.8% vs. 1.2 ± 1.5%, p = 0.005, in the atrial fibrillation group and 32.8 ± 18.6% vs. 4.6 ± 8.1%, p = 0.003, in the sinus group), suggesting that most TUNEL-positive myocytes were undergoing DNA repair. In addition, the incidence of TUNEL-positive myocytes significantly and positively correlated with the incidence of PCNA-positive myocytes (r = 0.5, p < 0.03 in the right atria; r = 0.661, p < 0.04 in the left atria). Conclusions: Cell death by apoptosis occurs in a small percentage of atrial cardiomyocytes in mitral and tricuspid valve diseases and DNA repair is more important and preserves the cardiomyocytes.