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Kobayashi Shigeki

Affiliate Master Yamaguchi University

Publish Date (<span class="translation_missing" title="translation missing: en.view.asc">Asc</span>)
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
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
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
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
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
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 3-4 pp. 19 - 26
published_at 2023-12
Right ventricular (RV) dysfunction and its linked arrhythmias play a crucial role in determining the prognosis of pulmonary arterial hypertension (PAH). Our paper aimed to explore the potential protective effects of direct pharmacological intervention in the RV muscle using dantrolene (DAN), a stabilizer of the cardiac ryanodine receptor (RyR2), against RV dysfunction and arrhythmia in a rat model of monocrotaline (MCT)-induced PAH. To induce PAH, male 8-week-old Sprague-Dawley rats received MCT injections. The study also assessed the induction of ventricular tachycardia (VT) by catecholamines, examining RyR2-mediated Ca^{2+} release properties in isolated cardiomyocytes. Additionally, a pulmonary artery-banding model was established to evaluate the independent effects of chronic pressure overload on RV morphology and function. In the MCT-induced PAH rat model, findings revealed RV hypertrophy, dilation, and functional decline, resulting in 0% survival rate two months post-MCT induction. Conversely, chronic DAN treatment demonstrated improvements in these RV parameters and an 80% increase in survival. Furthermore, chronic DAN treatment prevented the dissociation of calmodulin from RyR2, inhibiting Ca^{2+} sparks and spontaneous Ca^{2+} transients in MCT-induced hypertrophied RV cardiomyocytes. Epinephrine induced VT in over 50% of rats with MCT-induced PAH, while chronic DAN treatment achieved complete suppression of VT. The paper concludes that stabilizing RyR2 with DAN holds promise as a novel therapeutic approach against the development of RV dysfunction and fatal arrhythmias associated with PAH.
Creators : Tanaka Shinji Yamamoto Takeshi Kobayashi Shigeki Yano Masafumi Publishers : Yamaguchi University School of Medicine