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Histone Modification Is Correlated With Reverse Left Ventricular Remodeling in Nonischemic Dilated Cardiomyopathy  Emiko Ito, PhD, Shigeru Miyagawa, MD,

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Presentation on theme: "Histone Modification Is Correlated With Reverse Left Ventricular Remodeling in Nonischemic Dilated Cardiomyopathy  Emiko Ito, PhD, Shigeru Miyagawa, MD,"— Presentation transcript:

1 Histone Modification Is Correlated With Reverse Left Ventricular Remodeling in Nonischemic Dilated Cardiomyopathy  Emiko Ito, PhD, Shigeru Miyagawa, MD, PhD, Satsuki Fukushima, MD, PhD, Yasushi Yoshikawa, MD, Shunsuke Saito, MD, PhD, Tetsuya Saito, MD, Akima Harada, MSc, Maki Takeda, PhD, Noriyuki Kashiyama, MD, Yuki Nakamura, MD, Motoko Shiozaki, PhD, Koichi Toda, MD, PhD, Yoshiki Sawa, MD, PhD  The Annals of Thoracic Surgery  Volume 104, Issue 5, Pages (November 2017) DOI: /j.athoracsur Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

2 Fig 1 (A) End-diastolic dimension, (B) end-systolic dimension, and (C) left ventricular ejection fraction were serially assessed by transthoracic echocardiography at the time of left ventricular assist device implantation (pre), at 3 months (3m) after left ventricular assist device implantation, and at the time of cardiac transplantation (post). (D) The plasma brain natriuretic peptide (BNP) level was assessed at the time of left ventricular assist device implantation (pre) and at the time of cardiac transplantation (post). Apical left ventricular tissue was histologically assessed by (E) periodic acid–Schiff staining to determine myocyte cell size and by (F) Masson trichrome staining to determine interstitial fibrosis at the time of left ventricular assist device implantation (pre) and at the time of cardiac transplantation (post). The p values were analyzed between pre and post. (*p < 0.05; **p < 0.01.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

3 Fig 1 (A) End-diastolic dimension, (B) end-systolic dimension, and (C) left ventricular ejection fraction were serially assessed by transthoracic echocardiography at the time of left ventricular assist device implantation (pre), at 3 months (3m) after left ventricular assist device implantation, and at the time of cardiac transplantation (post). (D) The plasma brain natriuretic peptide (BNP) level was assessed at the time of left ventricular assist device implantation (pre) and at the time of cardiac transplantation (post). Apical left ventricular tissue was histologically assessed by (E) periodic acid–Schiff staining to determine myocyte cell size and by (F) Masson trichrome staining to determine interstitial fibrosis at the time of left ventricular assist device implantation (pre) and at the time of cardiac transplantation (post). The p values were analyzed between pre and post. (*p < 0.05; **p < 0.01.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

4 Fig 2 Histone modification profiles in the left ventricle were assessed by immunohistolabeling for each related protein in the pre– and post–left ventricular assist device implantation samples. The degree of histone modification was statistically compared between the left ventricular samples of pre– and post–left ventricular assist device implantation and those of normal subjects. (*p < 0.05; **p < 0.01; H3K4me2 = histone H3 lysine 4 dimethylation; H3K4me3 = histone H3 lysine 4 trimethylation; H3K9ac = histone H3 lysine 9 acetylation; H3K9me2 = histone H3 lysine 9 dimethylation; H3K9me3 = histone H3 lysine 9 trimethylation; H4K20me3 = histone H4 lysine 20 trimethylation.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

5 Fig 3 Gene expression of (A) H3 lysine 9 (H3K9) methyltransferase, suppressor of variegation 3-9 homologue 1 (SUV39H1), (B) H3K9 demethylase, jumonji domain–containing 1A (JMJD1A), (C) jumonji domain–containing 2A (JMJD2A), and (D) jumonji domain–containing 2D (JMJD2D) in the left ventricle was assessed by real-time polymerase chain reaction in the samples at pre– and post–left ventricular assist device implantation. (**p < 0.01; GAPDH = glyceraldehyde-3-phosphate dehydrogenase.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

6 Fig 4 Gene expression of atrial natriuretic peptide (ANP) (A) and brain natriuretic peptide (BNP) (B) in the left ventricle was assessed by real-time polymerase chain reaction in the samples at pre– and post–left ventricular assist device implantation. (**p < 0.01; GAPDH = glyceraldehyde-3-phosphate dehydrogenase.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

7 Fig 5 Correlations in gene expressions of the individual cohorts were statistically assessed by Spearman’s method between (A) atrial natriuretic peptide (ANP) and histone H3 lysine 9 dimethylation (H3K9me2), (B) ANP and histone H3 lysine 9 trimethylation (H3K9me3), (C) brain natriuretic peptide (BNP) and H3K9me2, and (D) BNP and H3K9me3. (mRNA = messenger ribonucleic acid; r = correlation coefficient.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

8 Supplemental Fig S1 The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions


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