Expression of spliceosome assembly factor SC-35 in TUNEL-positive atrial cardiomyocytes in mitral and tricuspid regurgitation: viability of atrial cardiomyocytes.
BACKGROUND
Most of the atrial cardiomyocytes with positive terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end-labelling (TUNEL) reaction are not apoptotic in patients with mitral and tricuspid valve diseases. The TUNEL-positive myocytes with expression of spliceosome assembly factor SC-35, an indicator of increased RNA synthesis, should be living cardiomyocytes.


METHODS
This study analyzed twenty-three patients with significant mitral and tricuspid regurgitation. Fifteen patients had persistent atrial fibrillation, and eight had sinus rhythm. Atrial appendageal tissues were obtained during surgery. Immunohistochemical study was performed.


RESULTS
Immunohistochemical study of fibrillating right atrial myocardium demonstrated that 44.8 ± 24.6% of myocytes had TUNEL-positive nuclei whereas 39.4 ± 21.4% of myocytes had TUNEL-positive nuclei in sinus right atrial myocardium (p=0.682). However, most (81.6%) nuclei of TUNEL-positive myocytes in the fibrillating right atria also expressed proliferating cell nuclear antigen (PCNA), an indicator of DNA replication and repair, and most nuclei (91.8%) of TUNEL-positive myocytes also expressed SC-35. In fibrillating left atria, most (88.1%) nuclei of TUNEL-positive myocytes also expressed SC-35. Similarly, in sinus right atrial myocardium, most (78.0%) nuclei of TUNEL-positive myocytes expressed PCNA, and most (91.4%) nuclei of TUNEL-positive myocytes also expressed SC-35, but none expressed Ki-67, a replication-associated antigen. Additionally, the percentage of TUNEL-positive myocytes in the right atria significantly and positively correlated with the percentage of PCNA-positive myocytes (r=0.826, p<0.001) and SC-35 positive myocytes (r=0.713, p<0.001).


CONCLUSIONS
Most TUNEL-positive atrial cardiomyocytes in patients with mitral and tricuspid regurgitation are living cardiomyocytes.
Chen
Mien-Cheng
MC
Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan, ROC. chenmien@ms76.hinet.net
Chang
Jen-Ping
JP
Ho
Wan-Chun
WC
Liu
Wen-Hao
WH
Chen
Chien-Jen
CJ
Yang
Cheng-Hsu
CH
Chen
Yung-Lung
YL
Tsai
Tzu-Hsien
TH
D000328:Adult; D000368:Aged; D020517:Atrial Appendage / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D012261:Ribonucleoproteins / Q000096:biosynthesis* / Q000235:genetics; D000068103:Serine-Arginine Splicing Factors; D017381:Spliceosomes / Q000378:metabolism*; D014262:Tricuspid Valve Insufficiency / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D012261:Ribonucleoproteins; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors