DOI: 10.1161/01.cir.99.21.2757. Significance of Myocytes With Positive DNA In Situ Nick End-Labeling (TUNEL) in Hearts With Dilated Cardiomyopathy

Significance of Myocytes With Positive DNA In Situ Nick End-Labeling (TUNEL) in Hearts With Dilated Cardiomyopathy

10.1161/01.cir.99.21.2757

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Circulation (276)

Abstract

Background —The presence of apoptotic myocytes has been reported in human hearts with dilated cardiomyopathy (DCM) on the basis of a positive finding of DNA in situ nick end-labeling (TUNEL). However, ultrastructural evidence of myocyte apoptosis has not been obtained. Methods and Results —A total of 80 endomyocardial biopsies were obtained from right and left ventricles of 20 patients with DCM and 20 normal control subjects. TUNEL-positive myocytes were found by light microscope in 15% of DCM specimens (controls, 0%, P <0.05), and the percentage of TUNEL-positive myocytes per section in DCM was 1.0±2.7% (mean±SD). According to TUNEL at the electron microscopic level (EM-TUNEL), immunogold particles, which label DNA breaks with 3′-OH terminals, were markedly accumulated in the bizarre-shaped nuclei, with widespread clumping of chromatin (so-called “hypertrophied nuclei”) of the myocytes obtained from DCM. Their ultrastructure was neither apoptotic nor necrotic but rather that of living cells. Taq polymerase–based DNA in situ ligation assay, which detects double-stranded DNA fragments more specifically than TUNEL, did not detect a positive reaction in any case. In mirror sections, all of the TUNEL-positive myocytes in DCM simultaneously expressed proliferating cell nuclear antigen, which is required for both DNA replication and repair, but Ki-67, a replication-associated antigen, was completely negative in all cases, which appeared to rule out cell proliferation activity. Conclusions —Most of the TUNEL-positive myocytes in hearts with DCM are not apoptotic but rather living cells with increasing activity of DNA repair.

Bibliography

Kanoh, M., Takemura, G., Misao, J., Hayakawa, Y., Aoyama, T., Nishigaki, K., Noda, T., Fujiwara, T., Fukuda, K., Minatoguchi, S., & Fujiwara, H. (1999). Significance of Myocytes With Positive DNA In Situ Nick End-Labeling (TUNEL) in Hearts With Dilated Cardiomyopathy. Circulation, 99(21), 2757â2764.

Authors 11

Motoo Kanoh (first)
Genzou Takemura (additional)
Jun Misao (additional)
Yukihiro Hayakawa (additional)
Takuma Aoyama (additional)
Kazuhiko Nishigaki (additional)
Toshiyuki Noda (additional)
Takako Fujiwara (additional)
Kazunori Fukuda (additional)
Shinya Minatoguchi (additional)
Hisayoshi Fujiwara (additional)

References 21 Referenced 239

10.1056/NEJM199610173351603
10.1056/NEJM199704173361603
10.1016/S0735-1097(97)00055-7
Arends MJ, Morris RG, Wyllie AH. Apoptosis: the role of the endonuclease. Am J Pathol. 1990;136:593–608. / Am J Pathol (1990)
10.1679/aohc.58.185
10.1161/circ.98.14.1422
10.1136/hrt.77.6.498
Kockx MM, Muhring J, Knaapen MWM, de Mayer GRY. RNA synthesis and splicing interferes with DNA in situ end labeling techniques used to detect apoptosis. Am J Pathol. 1998;152:885–888. / Am J Pathol (1998)
10.1083/jcb.135.5.1369
10.1161/circ.98.14.1355
10.1016/0092-8674(92)90416-A
10.1002/path.1711680202
10.1161/circ.93.5.841
Takemura G, Ohno M, Hayakawa Y, Kanoh M, Ohno A, Minatoguchi S, Uno Y, Fujiwara T, Fujiwara H. Role of apoptosis in the disappearance of infiltrated and proliferated interstitial cells after myocardial infarction. Circ Res. 1998;81:1130–1138. / Circ Res (1998)
10.1161/circ.63.6.6452971
10.1083/jcb.119.3.493
Maron BJ, Ferrans VJ, Roberts WC. Ultrastructural features of degenerated cardiac muscle cells in patients with cardiac hypertrophy. Am J Pathol. 1975;79:387–434. / Am J Pathol (1975)
10.1161/res.75.6.7955143
Hall PA, McKee PH, Menage HD, Dover R, Lane DP. High levels of p53 protein in UV-irradiated normal human skin. Oncogene. 1993;8:203–207. / Oncogene (1993)
10.1016/S0021-9258(17)32808-9
10.1002/jcp.1041540310

Dates

Type	When
Created	13 years, 2 months ago (June 11, 2012, 8:42 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 12:38 p.m.)
Indexed	1 month, 3 weeks ago (July 8, 2025, 7:31 a.m.)
Issued	26 years, 2 months ago (June 1, 1999)
Published	26 years, 2 months ago (June 1, 1999)
Published Print	26 years, 2 months ago (June 1, 1999)

Funders 0

None

BibTeX

@article{Kanoh_1999, title={Significance of Myocytes With Positive DNA In Situ Nick End-Labeling (TUNEL) in Hearts With Dilated Cardiomyopathy: Not Apoptosis but DNA Repair}, volume={99}, ISSN={1524-4539}, url={http://dx.doi.org/10.1161/01.cir.99.21.2757}, DOI={10.1161/01.cir.99.21.2757}, number={21}, journal={Circulation}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Kanoh, Motoo and Takemura, Genzou and Misao, Jun and Hayakawa, Yukihiro and Aoyama, Takuma and Nishigaki, Kazuhiko and Noda, Toshiyuki and Fujiwara, Takako and Fukuda, Kazunori and Minatoguchi, Shinya and Fujiwara, Hisayoshi}, year={1999}, month=jun, pages={2757–2764} }

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  "abstract": "<jats:p>\n            <jats:italic>Background</jats:italic>\n            \u2014The presence of apoptotic myocytes has been reported in human hearts with dilated cardiomyopathy (DCM) on the basis of a positive finding of DNA in situ nick end-labeling (TUNEL). However, ultrastructural evidence of myocyte apoptosis has not been obtained.\n          </jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results</jats:italic>\n            \u2014A total of 80 endomyocardial biopsies were obtained from right and left ventricles of 20 patients with DCM and 20 normal control subjects. TUNEL-positive myocytes were found by light microscope in 15% of DCM specimens (controls, 0%,\n            <jats:italic>P</jats:italic>\n            &lt;0.05), and the percentage of TUNEL-positive myocytes per section in DCM was 1.0\u00b12.7% (mean\u00b1SD). According to TUNEL at the electron microscopic level (EM-TUNEL), immunogold particles, which label DNA breaks with 3\u2032-OH terminals, were markedly accumulated in the bizarre-shaped nuclei, with widespread clumping of chromatin (so-called \u201chypertrophied nuclei\u201d) of the myocytes obtained from DCM. Their ultrastructure was neither apoptotic nor necrotic but rather that of living cells.\n            <jats:italic>Taq</jats:italic>\n            polymerase\u2013based DNA in situ ligation assay, which detects double-stranded DNA fragments more specifically than TUNEL, did not detect a positive reaction in any case. In mirror sections, all of the TUNEL-positive myocytes in DCM simultaneously expressed proliferating cell nuclear antigen, which is required for both DNA replication and repair, but Ki-67, a replication-associated antigen, was completely negative in all cases, which appeared to rule out cell proliferation activity.\n          </jats:p>\n          <jats:p>\n            <jats:italic>Conclusions</jats:italic>\n            \u2014Most of the TUNEL-positive myocytes in hearts with DCM are not apoptotic but rather living cells with increasing activity of DNA repair.\n          </jats:p>",
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