Yano Masafumi

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Medical Science & Innovation Volume 70 Issue 1-2 pp. 7 - 17
published_at 2023-06
To investigate whether dantrolene (DAN), cardiac ryanodine receptor (RyR2) stabilizer, improves impaired diastolic function in an early pressure-overloaded hypertrophied heart, pressure-overload hypertrophy was induced by transverse aortic constriction (TAC) in mice. Wild-type (WT) mice were divided into four groups: sham-operated mice (Sham), sham-operated mice treated with DAN (DAN+Sham), TAC mice (TAC), and TAC mice treated with DAN (DAN+TAC). The mice were then followed up for 2 weeks. Left ventricular (LV) hypertrophy was induced in TAC, but not DAN+TAC mice, 2 weeks after TAC. There were no differences in LV fractional shortening among the four groups. Catheter tip micromanometer showed that the time constant of LV pressure decay, an index of diastolic function, was significantly prolonged in TAC but not in DAN+TAC mice. Diastolic function was significantly impaired in TAC, but not in DAN+TAC mice as determined by cell shortening and Ca^{2+} transients. An increase in diastolic Ca^{2+} leakage and a decrease in calmodulin (CaM) binding affinity to RyR2 were observed in TAC mice, while diastolic Ca^{2+} leakage improved in DAN+TAC mice. Thus, DAN prevented the progression of hypertrophy and improved the impairment of LV relaxation by inhibiting diastolic Ca^{2+} leakage through RyR2 and the dissociation of CaM from RyR2.
Medical Science & Innovation Volume 70 Issue 1-2 pp. 1 - 6
published_at 2023-06
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by a single point mutation in the cardiac type 2 ryanodine receptor (RyR2). Using knock-in mouse (KI) model (R2474S/+), we previously reported that a single point mutation within the RyR2 sensitized the channel to agonists, primarily mediated by defective inter-domain interaction within the RyR2 and subsequent dissociation of calmodulin (CaM) from the RyR2. Here, we examined whether CPVT can be genetically rescued by enhancing the binding affinity of CaM to the RyR2. We first determined whether there was a possible amino-acid substitution within the CaM-binding domain in the RyR2 (3584-3603) that can enhance its binding affinity to CaM, and found that V3599K substitution showed the highest binding affinity of CaM to CaM-binding domain. Hence, we generated a heterozygous KI mouse model (V3599K/+) with a single amino acid substitution in the CaM-binding domain of the RyR2, and crossbred it with the heterozygous CPVT –associated R2474S/+ KI mouse to obtain a double heterozygous R2474S/V3599K KI mouse model. The CPVT phenotypes, bidirectional or polymorphic ventricular tachycardia, were inhibited in the R2474S/V3599K mice. Thus, enhancement of the CaM binding affinity of the RyR2 is essential to prevent CPVT-associated arrhythmogenesis.
Creators : Nakamura Yoshihide Yamamoto Takeshi Kobayashi Shigeki Yano Masafumi Publishers : Yamaguchi University School of Medicine
Aberrant increases in protein phosphatase 1(PP1) activity have been shown to be associated with inefficient sarcoplasmic reticulum Ca^{2+} cycling, leading to cardiac dysfunction in the failing heart. In the present study, we investigated whether BNP promoter-inducible suppression of PP1β would ameliorate progression of pressure overload-induced heart failure in mice, a clinically relevant animal model. An Adeno-associated virus 9 (AAV9) vector encoding PP1βshRNA and a negative control (NC) shRNA driven by a brain natriuretic peptide (BNP) promoter with an emerald green fluorescent protein expression (EmGFP) cassette were used to test the hypothesis. AAV9 vectors (AAV9-BNP-EmGFP-PP1βshRNA and AAV9-BNP-EmGFP-NCshRNA) were introduced into the in vivo heart via the tail vein injection (4x10^{11} GC/mice) in 8-week-old C57BL6J mice, followed by transverse aortic constriction (TAC) 2 weeks after the AAV9 vector injection. Post TAC cardiac function was sequentially assessed every 2 week by echocardiography, followed by hemodynamic assessment at 1 month. AAV9-BNP-EmGFP-PP1βshRNA treatment suppressed myocardial PP1β expression by 15% compared with the NCshRNA group (p<0.001). The fractional shortening (%FS) of the left ventricle in the PP1βshRNA-treated group was significantly larger than the NCshRNA-treated group (21%±1.0% vs. 15%±0.01, p<0.01). The ratios of heart weight (HW) / body weight (BW) and lung weight (LW) / BW in the PP1βshRNA group were significantly smaller than those of the NCshRNA group (HW/BW: 9.20±0.49 vs. 10.6±0.45 mg/g
Creators : Shiraishi Kozo Ikeda Yasuhiro Miyazaki Yosuke Fujimoto Shizuka N. Yoshimura Koichi Miura Toshiro Matsuzaki Masanori Yano Masafumi Publishers : Yamaguchi University School of Medicine
山口医学 Volume 66 Issue 2 pp. 89 - 96
published_at 2017-05-01
Background The lipid-lowering therapy by statins may stabilize and reduce coronary plaques. We compare the effect of strong or moderate statins on the coronary plaque characteristics by using 64-slice multidetector computed tomography (MDCT). Methods and Results We analyzed 13 subjects with non-calcified coronary plaques(NCP)as determined by MDCT. Pitavastatin(PTV:2mg/day)or pravastatin(PRA:10mg/day)were randomly administered. MDCT were performed at 0, 6 and 12 months after lipid-lowering therapy. In PTV group(n=6),CT density of NCP increased by 35.6 ± 28.8 HU after 6 months(p=0.037)and by 30.6 ± 29.8 HU after 12 months(NS).NCP area was decreased by 35.9 ± 15.2 % after 6 months and by 41.0 ± 16.5 % after 12 months(both P=0.001).In PRA group(n=7),CT density of NCP did not significantly increased after 6 months(NS)and after 12 months(NS).NCP area was not significantly decreased at 6 months(NS),but decreased by 23.1 ± 16.7 % at 12 months(P=0.001). Conclusions Serial CT angiography revealed that the regression of NCP occurs rapidly by strong lipid lowering therapy compared to the moderate statin therapy.
Creators : Nao Tomoko Miura Toshiro Yoshimura Masayuki Fujimura Tatsuhiro Nakashima Yoshiteru Okada Munemasa Matsunaga Naofumi Yano Masafumi Publishers : 山口大学医学会
山口医学 Volume 65 Issue 4 pp. 161 - 166
published_at 2016-11-01
Creators : Murata Yoriyuki Aoe Keisuke Utsunomiya Toshiaki Sakamoto Kenji Oishi Keiji Kohtoku Wataru Chikamori Kenichi Maeda Tadashi Okabe Kazunori Murakami Tomoyuki Yano Masafumi Ueoka Hiroshi Publishers : 山口大学医学会
Background: Angiotensin II (AngII) increases reactive oxygen species (ROS) and induces glomerular sclerosis. Toll-like receptor 4 (TLR4)-mediated inflammation enhances the renal impairment in renal inflammatory diseases. The relationship between TLR4 and AngII-induced glomerular sclerosis is unknown.Methods: Mice lacking TLR4 function (Tlr4^{lps-d}) and wild-type (WT) mice were randomized into groups treated with AngII, norepinephrine (NE) or a sub-depressor dose of the AngII receptor blocker irbesartan along with AngII for 2 weeks. We then assessed the expressions of NADPH oxidase and monocyte chemoattractant protein-1 (MCP-1) and the inflammatory cell recruitment in the glomeruli. We also evaluated the mesangial matrix proliferation and ROS.Results: AngII and NE equally increased the systolic blood pressure compared to the control mice (p<0.05). In the WT mice treated with AngII, we observed glomerular sclerosis, an increase in NADPH oxidase, MCP-1 and the infiltration of macrophages as well as ROS content in the glomeruli compared to the control mice (p<0.05), whereas the Tlr4^{lps-d} mice showed little effects of AngII on these indices. In addition, the sub-depressor-dose irbesartan treatment reversed these changes. NE had little effects on these indices. Conclusions: TLR4 plays an important role in AngII-induced oxidative stress, inflammation and glomerular sclerosis through the AT1 receptor.
Creators : Okamoto Tadashi Umemoto Seiji Yoshimura Koichi Sakumura Toshihiro Murata Tomoaki Fukai Tohru Yano Masafumi Matsuzaki Masanori Publishers : Yamaguchi University School of Medicine
We investigated the relationship between myocardial oxidative stress and cardiac sympathetic hyperactivity in patients with takotsubo cardiomyopathy (TC) compared with acute anteroseptal myocardial infarction (AMI). Methods: In 10 TC patients and 10 AMI patients, electrocardiogram, echocardiography, cardiac catheterization were conducted, and plasma catecholamines and urinary (U) 8-hydroxy-2’-deoxyguanosine (8-OHdG) as a marker of oxidative DNA damage were taken for one week from onset. Results: On admission, the coronary sinus (CS) had significantly higher norepinephrine (NE) and 8-OHdG levels than the aortic root (Ao) and peripheral blood vessels. Circulating catecholamines in TC patients tended to be higher than those in AMI patients
Cardiology (Switzerland) Volume 127 Issue 2 pp. 105 - 113
published_at 2014-01
Creators : Kobayashi Shigeki Murakami Wakako Myoren Takeki Tateishi Hiroki Okuda Shinichi Doi Masahiro Nao Tomoko Wada Yasuaki Matsuzaki Masunori Yano Masafumi Publishers : Karger
Gan To Kagaku Ryoho Volume 40 Issue 12 pp. 1936 - 1938
published_at 2013-11
Creators : 来嶋 大樹 Kandkiyo Shinsuke 中須賀 千代 井上 由佳 新藤 芳太郎 筒井 理仁 吉野 茂文 久保 誠 矢野 雅文 尾本 雅彦 神田 隆 硲 彰一 岡 正朗 Publishers : 癌と化学療法社
JACC: Heart Failure Volume 1 Issue 6 pp. 459 - 466
published_at 2013-12
Creators : Fujita Takashi Fujino Noboru Anan Ryuichiro Tei Chuwa Kubo Toru Doi Yoshinori Kinugawa Shintaro Tsutsui Hiroyuki Kobayashi Shigeki Yano Masafumi Asakura Masanori Kitakaze Masafumi Komuro Issei Konno Tetsuo Hayashi Kenshi Kawashiri Masaaki Ino Hidekazu Yamagishi Masakazu Publishers : Elsevier
Circulation Journal Volume 78 Issue 3 pp. 772 - 774
published_at 2013
Creators : Tateishi Hiroki Okamura Takayuki Yamada Jutaro Nao Tomoko Maeda Takao Oda Takamasa Nakamura Takeshi Miura Toshiro Matsuzaki Masunori Yano Masafumi Publishers : Japanese Circulation Society
Circulation Journal Volume 77 Issue 7 pp. 1684 - 1686
published_at 2013
Creators : Okuda Shinichi Yano Masafumi Publishers : Japanese Circulation Society
山口医学 Volume 63 Issue 1 pp. 11 - 16
published_at 2014-02-01
Creators : Yano Masafumi Publishers : 山口大学医学会
Creators : Akashi Shintaro Miura Toshiro Shibuya Masaki Fukagawa Yasuhiro Oda Takamasa Nakamura Takeshi Ikeda Yasuhiro Matsuzaki Masunori Yano Masafumi Publishers : Yamaguchi University School of Medicine
Creators : Fukagawa Yasuhiro Miura Toshiro Shibuya Masaki Akashi Shintaro Oda Takamasa Nakamura Takeshi Matsuzaki Masunori Yano Masafumi Publishers : Yamaguchi University School of Medicine
Journal of Cardiology Cases Volume 8 Issue 4 pp. 134 - 137
published_at 2013-10
Creators : Kinbara Terufumi Hayano Tomoko Otani Nozomu Furutani Yuhji Murakami Tomoyuki Yano Masafumi Publishers : ELSEVIER
Clinical Calcium Volume 23 Issue 4 pp. 471 - 480
published_at 2013-04
Creators : Okuda Shinichi Yano Masafumi Publishers : 医薬ジャーナル社
日本薬理学雑誌 Volume 140 Issue 6 pp. 250 - 254
published_at 2012
Creators : Yano Masafumi Yamamoto Takeshi Kobayashi Shigeki Matsuzaki Masunori Publishers : 日本薬理學會編輯部
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by stress- or exercise- induced ventricular tachycardia, frequently leading to sudden cardiac death. A considerable body of evidence accumulated over recent years suggests that mutation-linked cardiac ryanodine receptor (RyR2) defects cause Ca^2+ leak from sarcoplasmic reticulum, which triggers delayed afterdepolarization and leads to CPVT. However, the underlying mechanism, by which a single mutation in such a large molecule causes drastic effects on the channel function, remains elusive. Here we report that introduction of a human CPVT mutation S2246L into the mouse RyR2 induces aberrant activation of channel gating by forming abnormally tight domain-domain interaction between the S2246L mutable domain and the K201-binding domain. This produces more global conformational change in the RyR2: namely, an aberrant domain unzipping between the N-terminal (a.a. 1–600) domain and the central (a.a. 2000–2500) domain owing to the allosteric conformational coupling mechanism. Pharmacological correction of the defective inter-domain interactions can stop the aberrant Ca^2+ release and lethal arrhythmia. These results provide a new pathogenic mechanism of CPVT and a novel therapeutic strategy against CPVT
Creators : Suetomi Takeshi Yano Masafumi Matsuzaki Masanori Publishers : Yamaguchi University School of Medicine
European journal of heart failure : journal of the Working Group on Heart Failure of the European Society of Cardiology Volume 13 Issue 1 pp. 29 - 36
published_at 2011-01
Creators : Kobayashi Shigeki Susa Takehisa Tanaka Takeo Wada Yasuaki Okuda Shinichi Doi Masahiro Nao Tomoko Yoshiga Yasuhiro Yamada Jutaro Okamura Takayuki Ueyama Takeshi Kawamura Syuji Yano Masafumi Matsuzaki Masunori Publishers : Elsevier | European Society of Cardiology
日本臨床 Volume 69 Issue 増刊9 pp. 595 - 604
published_at 2011-11
Creators : 奥田 真一 矢野 雅文 Publishers : 日本臨牀社
Cardiovascular research Volume 89 Issue 1 pp. 79 - 88
published_at 2011-01-01
Creators : Aoyama Hidekazu Ikeda Yasuhiro Miyazaki Yosuke Yoshimura Koichi Nishino Shizuka Yamamoto Takeshi Yano Masafumi Inui Makoto Aoki Hiroki Matsuzaki Masunori Publishers : British Medical Association | Elsevier Science
山口医学 Volume 54 Issue 4 pp. 109 - 115
published_at 2005-08-31
Creators : Inoue Noriko Ohkusa Tomoko Nao Tomoko Lee Jong Kook Matsumoto Tomo Hisamatsu Yuji Satoh Takashi Yano Masafumi Yasui Kenji Kodama Itsuo Publishers : 山口大学医学会
Creators : Oda Tetsuro Yano Masafumi Matsuzaki Masunori Publishers : Yamaguchi University School of Medicine
Creators : Yano Masafumi Publishers : Yamaguchi University Graduate School of Medicine