Article
Medicine, General & Internal
Irene Hiniesto-Inigo, Laura M. Castro-Gonzalez, Valentina Corradi, Mark A. Skarsfeldt, Samira Yazdi, Siri Lundholm, Johan Nikesjo, Sergei Yu Noskov, Bo Hjorth Bentzen, D. Peter Tieleman, Sara I. Liin
Summary: In this study, the researchers investigated the potential modulation of the cardiac voltage-gated potassium channel KV7.1/KCNE1 by endocannabinoids. They found that certain endocannabinoids facilitate channel activation and have protective effects in Long QT Syndrome.
Article
Cardiac & Cardiovascular Systems
Cherry Alexander, Martin J. Bishop, Rebecca J. Gilchrist, Francis L. Burton, Godfrey L. Smith, Rachel C. Myles
Summary: This study demonstrates that activation of L-type calcium channels (LTCC) at sites displaying steep voltage gradients generates premature ventricular complexes (PVCs) which induce polymorphic ventricular tachycardia (TdP), providing a mechanism and rationale for using LTCC blockers as a novel therapeutic approach in long QT syndrome (LQTS).
CARDIOVASCULAR RESEARCH
(2023)
Article
Medicine, General & Internal
Jose Alberto Navarro-Garcia, Rafael Salguero-Bodes, Laura Gonzalez-Lafuente, Laura Martin-Nunes, Elena Rodriguez-Sanchez, Teresa Bada-Bosch, Eduardo Hernandez, Evangelina Merida-Herrero, Manuel Praga, Jorge Solis, Fernando Arribas, Hector Bueno, Makoto Kuro-O, Maria Fernandez-Velasco, Luis Miguel Ruilope, Carmen Delgado, Gema Ruiz-Hurtado
Summary: This study found that the FGF23-Klotho axis is associated with cardiac arrhythmias in CKD patients. The increase in FGF23 levels in CKD patients is related to prolonged QT intervals. Experimental results show that FGF23 can induce QT prolongation in healthy mice. This prolongation and changes in cardiac repolarization were also observed in Nfx mice and Klotho deficient mice.
Article
Cardiac & Cardiovascular Systems
Koichi Kato, Holly M. Isbell, Veronique Fressart, Isabelle Denjoy, Amal Debbiche, Hideki Itoh, Jacques Poinsot, Alfred L. George, Alain Coulombe, Madeline A. Shea, Pascale Guicheney
Summary: This study identified a novel CALM3 variant, p.N138K, associated with LQTS and compared its pathogenicity with a severe LQTS phenotype associated with p.D130G-CaM variant. The p.N138K variant impairs Ca2+-binding affinity of CaM and I-CaL inactivation but potentiates I-Ks. The variable clinical phenotype of this variant compared with previously published de novo LQTS-CaM variants can be explained by a milder impairment of I-CaL inactivation combined with I-Ks augmentation.
CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Dena Esfandyari, Bio Maria Gheo Idrissou, Konstantin Hennis, Petros Avramopoulos, Anne Dueck, Ibrahim El-Battrawy, Laurenz Grueter, Melanie Annemarie Meier, Anna Christina Naeger, Deepak Ramanujam, Tatjana Dorn, Thomas Meitinger, Christian Hagl, Hendrik Milting, Martin Borggrefe, Stefanie Fenske, Martin Biel, Andreas Dendorfer, Yassine Sassi, Alessandra Moretti, Stefan Engelhardt
Summary: MicroRNA-365 regulates human cardiac action potential by modulating key cardiac repolarizing channels.
NATURE COMMUNICATIONS
(2022)
Article
Cardiac & Cardiovascular Systems
Takanori Aizawa, Yuko Wada, Kanae Hasegawa, Hai Huang, Tomohiko Imamura, Jingshan Gao, Asami Kashiwa, Hirohiko Kohjitani, Megumi Fukuyama, Koichi Kato, Eri Toda Kato, Takashi Hisamatsu, Seiko Ohno, Takeru Makiyama, Takeshi Kimura, Minoru Horie
Summary: This study aimed to investigate the clinical phenotypes of LQT2 patients, with one-third of the patients carrying KCNH2 non-missense variants resulting in haploinsufficiency (HI). These patients exhibited milder phenotypes. The remaining two-thirds of patients had missense variants causing trafficking deficiency and resulting in either haploinsufficiency (HI) or dominant-negative (DN) effects. Through molecular mechanism studies, we were able to better predict the clinical outcomes in the patients.
Article
Pharmacology & Pharmacy
Chunyun Du, Randall L. Rasmusson, Glenna C. Bett, Brandon Franks, Henggui Zhang, Jules C. Hancox
Summary: The aim of this study was to establish the effects of the D172N mutation on ventricular repolarization through real-time replacement of I-K1 using the dynamic clamp technique. The results showed that the D172N mutation significantly abbreviated AP duration and accelerated maximal AP repolarization velocity, with no significant hyperpolarization of resting potential.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maliheh Najari Beidokhti, Alexander C. Bertalovitz, Weizhen Ji, Jorge McCormack, Lauren Jeffries, Emily Sempou, Mustafa K. Khokha, Thomas V. McDonald, Saquib A. Lakhani
Summary: Next-generation sequencing platforms are increasingly used in clinical genetic settings to improve diagnostic accuracy in families with suspected heritable diseases. A functional testing approach was described in this study to identify potential genetic variants associated with long QT syndrome in a family, leading to precise diagnosis and personalized clinical management. Functional characterization was found to be a valuable adjunct to in silico analyses of whole exome sequencing results.
MOLECULAR GENETICS AND GENOMICS
(2021)
Article
Cardiac & Cardiovascular Systems
Alexander M. Kaizer, Annika Winbo, Sally-Ann B. Clur, Susan P. Etheridge, Michael J. Ackerman, Hitoshi Horigome, Ulrike Herberg, Federica Dagradi, Carla Spazzolini, Stacy A. S. Killen, Annette Wacker-Gussmann, Arthur A. M. Wilde, Elena Sinkovskaya, Alfred Abuhamad, Margherita Torchio, Chai-Ann Ng, Annika Rydberg, Peter J. Schwartz, Bettina F. Cuneo
Summary: The study evaluates the effects of various factors on fetal heart rate (FHR) in pregnancies with familial long QT syndrome (LQTS) and develops a FHR/GA threshold for predicting LQTS type 1 (LQT1) and LQT2 with high accuracy, sensitivity, and specificity.
Article
Multidisciplinary Sciences
Marion Pierre, Mohammed Djemai, Hugo Poulin, Mohamed Chahine
Summary: Cardiomyocytes derived from patient-specific induced pluripotent stem cells successfully model the pathogenic mechanisms of various channelopathies, including experiments involving knockout of the cardiac sodium channel. A Na(V)1.5 KO iPSC line capable of differentiating into cardiomyocytes was developed using CRISPR/Cas9 technology. Changes in action potentials (APs) and electrophysiological properties in Na(V)1.5 KO iPSC-CMs, as well as the impact of a long QT syndrome 3 (LQT3) variant on Na+ channel function, were observed.
SCIENTIFIC REPORTS
(2021)
Article
Physiology
Xinle Zou, Xiaoan Wu, Kevin J. Sampson, Henry M. Colecraft, H. Peter Larsson, Robert S. Kass
Summary: This study investigates the potential of compounds ML277 and R-L3 as treatment options for LQT1 and LQT5 mutant channels. The results show that ML277 and R-L3 can enhance mutant channel currents and slow down current deactivation, suggesting their potential utility in specific LQTS therapeutics.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Marina Rieder, Paul Kreifels, Judith Stuplich, David Ziupa, Helge Servatius, Luisa Nicolai, Alessandro Castiglione, Christiane Zweier, Babken Asatryan, Katja E. Odening
Summary: This study aimed to assess the association of different electrical parameters with the genotype and symptoms in patients with LQTS. The results showed that electrical parameters can distinguish between symptomatic and asymptomatic patients with different genetic forms of LQTS.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Physiology
Majid K. Al Salmani, Rezvan Tavakoli, Wajid Zaman, Ahmed Al Harrasi
Summary: This study investigated the effects of the T1019PfsX38 mutation on hERG channels. The results showed that the T1019PfsX38 mutation accelerated the deactivation rate of hERG channels and shifted the voltage dependence of inactivation in the negative direction. In addition, the mutant variant showed reduced outward currents and integrals during membrane repolarization. These changes may contribute to the pathology seen in LQT2 patients.
PHYSIOLOGICAL REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Chunyun Du, Henggui Zhang, Stephen C. Harmer, Jules C. Hancox
Summary: The T618I KCNH2-encoded hERG mutation is the most frequent mutation in congenital short QT syndrome (SQTS) and affects cardiac currents and action potentials. This mutation exacerbates repolarizing differences between Purkinje fiber and ventricular action potentials, which may contribute to U waves in T618I carriers. However, it has a smaller effect on atrial action potentials, which may help explain the absence of reported atrial fibrillation in T618I carriers.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cardiac & Cardiovascular Systems
Megumi Fukuyama, Minoru Horie, Hisaaki Aoki, Junichi Ozawa, Koichi Kato, Yuichi Sawayama, Sachiko Tanaka-Mizuno, Takeru Makiyama, Masao Yoshinaga, Yoshihisa Nakagawa, Seiko Ohno
Summary: School-based ECG screenings in Japan are effective in identifying young patients with long QT syndrome (LQTS) who require genetic analysis. Students with prolonged QT intervals during regular screenings are more likely to have risk factors for LQTS, and they have fewer symptomatic patients compared to clinically consulted patients. Screening at a younger age allows for early identification of at-risk patients and provision of preventative treatments.
Article
Anesthesiology
Kei Nakahira, Kensuke Oshita, Masayuki Itoh, Makoto Takano, Yoshiro Sakaguchi, Keiko Ishihara
ANESTHESIA AND ANALGESIA
(2016)
Article
Biochemistry & Molecular Biology
Kazuhiro Sakamaki, Takahiro M. Ishii, Toshiya Sakata, Kiwamu Takemoto, Chiyo Takagi, Ayako Takeuchi, Ryo Morishita, Hirotaka Takahashi, Akira Nozawa, Hajime Shinoda, Kumiko Chiba, Haruyo Sugimoto, Akiko Saito, Shuhei Tamate, Yutaka Satou, Sang-Kee Jung, Satoshi Matsuoka, Koji Koyamada, Tatsuya Sawasaki, Takeharu Nagai, Naoto Ueno
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2016)
Article
Neurosciences
Yuzo Murata, Toshiharu Yasaka, Makoto Takano, Keiko Ishihara
NEUROSCIENCE LETTERS
(2016)
Article
Physiology
Keiko Ishihara
JOURNAL OF GENERAL PHYSIOLOGY
(2018)
Article
Multidisciplinary Sciences
Bongju Kim, Ayako Takeuchi, Masaki Hikida, Satoshi Matsuoka
SCIENTIFIC REPORTS
(2016)
Article
Cell Biology
Ayako Takeuchi, Bongju Kim, Satoshi Matsuoka
Review
Neurosciences
Ayako Takeuchi, Satoshi Matsuoka
JOURNAL OF PHYSIOLOGY-LONDON
(2020)
Article
Physiology
Mohammed M. Islam, Ayako Takeuchi, Satoshi Matsuoka
JOURNAL OF PHYSIOLOGICAL SCIENCES
(2020)
Article
Cell Biology
Ayako Takeuchi, Satoshi Matsuoka
Summary: NCLX plays a significant role in the forward mode of mitochondrial Na+-Ca2+ exchange activity in isolated mouse brain mitochondria. However, the Na+-dependent Ca2+ influx into mitochondria (reverse mode) appears to be insensitive to the blockers tested, indicating the presence of unidentified Ca2+ transport systems.
Review
Biochemistry & Molecular Biology
Ayako Takeuchi, Satoshi Matsuoka
Summary: The gene SLC24A6/SLC8B1 has been identified as the responsible gene for mitochondrial Na+-Ca2+ exchange for over 10 years, leading to a deeper understanding of the structure-function relationships and physiological/pathophysiological contributions of NCLX. Recent achievements regarding NCLX, focusing on its heart-specific characteristics, biophysical properties, spatial distribution in cardiomyocytes, and roles in cardiac functions under physiological and pathophysiological conditions, have been summarized in this review.
Article
Cardiac & Cardiovascular Systems
Yukari Takeda, Satoshi Matsuoka
Summary: Mitochondria play a role in regulating local calcium release (LCR) generation by modulating sarcoplasmic reticulum (SR) Ca2+ content through NCXm-mediated Ca2+ efflux in murine sinoatrial nodal cells (SANCs). Inhibiting mitochondrial Ca2+ efflux using an NCXm inhibitor reduces the amplitude and duration of LCR, prolongs LCR period and cycle length (CL), and impacts the Ca2+ transient. This study sheds light on the spatial and functional association between mitochondria and LCR in SANCs.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ayako Takeuchi, Satoshi Matsuoka
Summary: In this study, the spatial and functional coupling between mitochondrial Na+-Ca2+ exchanger (NCLX) and sarcoplasmic reticulum Ca2+ pump SERCA in cardiomyocytes was investigated. The results demonstrated a close interaction between NCLX and SERCA, indicating their important role in modulating cellular functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Meeting Abstract
Biophysics
Mohammed M. Islam, Ayako Takeuchi, Satoshi Matsuoka
BIOPHYSICAL JOURNAL
(2020)
Article
Cardiac & Cardiovascular Systems
Yaopeng Hu, Yubin Duan, Ayako Takeuchi, Lin Hai-Kurahara, Jun Ichikawa, Keizo Hiraishi, Tomohiro Numata, Hiroki Ohara, Gentaro Iribe, Michio Nakaya, Masayuki X. Mori, Satoshi Matsuoka, Genshan Ma, Ryuji Inoue
CARDIOVASCULAR RESEARCH
(2017)
Meeting Abstract
Biophysics
Ayako Takeuchi, Ryuta Saito, Yukiko Himeno, Satoshi Matsuoka
BIOPHYSICAL JOURNAL
(2017)
Article
Cardiac & Cardiovascular Systems
Andrew B. Harvey, Renelyn A. Woltes, Raymond N. Deepe, Hannah G. Tarolli, Jenna R. Drummond, Allison Trouten, Auva Zandi, Jeremy L. Barth, Rupak Mukherjee, Martin J. Romeo, Silvia G. Vaena, Ge Tao, Robin Muise-Helmericks, Paula S. Ramos, Russell A. Norris, Andy Wessels
Summary: This study highlights the importance of SOX9 in the regulation of epicardial cell invasion and emphasizes the role of EPDCs in regulating atrioventricular valve development and homeostasis. It also reports a novel expression profile of Cd109, a gene with previously unknown relevance in heart development.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Review
Cardiac & Cardiovascular Systems
MariaSanta C. Mangione, Jinhua Wen, Dian J. Cao
Summary: mTOR, a mechanistic target of rapamycin, is an evolutionarily conserved pathway that plays a fundamental role in nutrient sensing, growth, metabolism, lifespan, and aging. Recent studies have highlighted the regulatory role of mTOR in innate immune responses and its involvement in the pathogenesis of cardiovascular diseases, especially in acute inflammation and atherosclerotic cardiovascular disease. This review also discusses mTOR's role in trained immunity, immune senescence, and clonal hematopoiesis, as well as its architecture and regulatory complexes.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Junlin Li, Yajun Gong, Yiren Wang, Huihui Huang, Huan Du, Lianying Cheng, Cui Ma, Yongxiang Cai, Hukui Han, Jianhong Tao, Gang Li, Panke Cheng
Summary: Myocardial ischemia-reperfusion injury is closely related to the final infarct size in acute myocardial infarction. Regulatory T cells play an important role in the inflammatory response after AMI, but different subtypes of Tregs have different effects on the injury.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Yuxin Chu, Yutao Hua, Lihao He, Jin He, Yunxi Chen, Jing Yang, Ismail Mahmoud, Fanfang Zeng, Xiaochang Zeng, Gloria A. Benavides, Victor M. Darley-Usmar, Martin E. Young, Scott W. Ballinger, Sumanth D. Prabhu, Cheng Zhang, Min Xie
Summary: This study demonstrates that administering beta-hydroxybutyrate (beta-OHB) at the time of reperfusion can reduce infarct size and preserve cardiac function by activating autophagy and preserving mitochondrial homeostasis, potentially through mTOR inhibition.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)