Quantification of DNA Damage in Heart Tissue as a Novel Prediction Tool for Therapeutic Prognosis of Patients With Dilated Cardiomyopathy

Toshiyuki Ko, MD, PhD; Kanna Fujita, MD; Seitaro Nomura, MD, PhD; Yukari Uemura, PhD; Shintaro Yamada, MD; Takashige Tobita, MD; Manami Katoh, MD, PhD; Masahiro Satoh, MD, PhD; Masamichi Ito, MD, PhD; Yukako Domoto, MD, PhD; Yumiko Hosoya, MD, PhD; Eisuke Amiya, MD, PhD; Masaru Hatano, MD, PhD; Hiroyuki Morita, MD, PhD; Masashi Fukayama, MD, PhD; Hiroyuki Aburatani, MD, PhD; Issei Komuro, MD, PhD

JACC: Basic to Translational Science (Oct 2019)

Quantification of DNA Damage in Heart Tissue as a Novel Prediction Tool for Therapeutic Prognosis of Patients With Dilated Cardiomyopathy

Toshiyuki Ko, MD, PhD,
Kanna Fujita, MD,
Seitaro Nomura, MD, PhD,
Yukari Uemura, PhD,
Shintaro Yamada, MD,
Takashige Tobita, MD,
Manami Katoh, MD, PhD,
Masahiro Satoh, MD, PhD,
Masamichi Ito, MD, PhD,
Yukako Domoto, MD, PhD,
Yumiko Hosoya, MD, PhD,
Eisuke Amiya, MD, PhD,
Masaru Hatano, MD, PhD,
Hiroyuki Morita, MD, PhD,
Masashi Fukayama, MD, PhD,
Hiroyuki Aburatani, MD, PhD,
Issei Komuro, MD, PhD

Affiliations

Toshiyuki Ko, MD, PhD: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Kanna Fujita, MD: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Seitaro Nomura, MD, PhD: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Yukari Uemura, PhD: Biostatistics Division, Clinical Research Support Center, University of Tokyo Hospital, Tokyo, Japan
Shintaro Yamada, MD: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Takashige Tobita, MD: Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan
Manami Katoh, MD, PhD: Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan
Masahiro Satoh, MD, PhD: Department of Cardiovascular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
Masamichi Ito, MD, PhD: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Yukako Domoto, MD, PhD: Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Yumiko Hosoya, MD, PhD: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Eisuke Amiya, MD, PhD: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Masaru Hatano, MD, PhD: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Hiroyuki Morita, MD, PhD: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Masashi Fukayama, MD, PhD: Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Hiroyuki Aburatani, MD, PhD: Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan
Issei Komuro, MD, PhD: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Address for correspondence: Dr. Issei Komuro, Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Journal volume & issue: Vol. 4, no. 6
pp. 670 – 680

Abstract

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Summary: This study evaluated myocardial nuclear staining for the DNA damage markers poly(ADP-ribose) (PAR) and γ-H2A.X in 58 patients with dilated cardiomyopathy. Patients with left ventricular reverse remodeling (LVRR) showed a significantly smaller proportion of PAR-positive nuclei and γ-H2A.X–positive nuclei in biopsy specimens compared with those without LVRR. Propensity analysis showed that the proportion of both PAR-positive and γ-H2A.X–positive nuclei were independent prognostic factors for LVRR. In conclusion, we showed the utility of DNA damage-marker staining to predict the probability of LVRR, thus revealing a novel prognostic predictor of medical therapy for dilated cardiomyopathy. Key Words: dilated cardiomyopathy, DNA damage, left ventricular reverse remodeling, poly ADP-ribose

Published in JACC: Basic to Translational Science

ISSN: 2452-302X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.journals.elsevier.com/jacc-basic-to-translational-science/

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