A5005948118- Atrial Fibrillation Management and Outcomes
- Cardiac Arrhythmias and Treatments
- Cardiac electrophysiology and arrhythmias
- Cardiac pacing and defibrillation studies
- Cardiovascular Effects of Exercise
- ECG Monitoring and Analysis
- RNA Research and Splicing
- Cardiovascular Syncope and Autonomic Disorders
- Cardiac Valve Diseases and Treatments
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
- Endoplasmic Reticulum Stress and Disease
- Cardiac Fibrosis and Remodeling
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Autophagy in Disease and Therapy
- Cell Adhesion Molecules Research
- Tissue Engineering and Regenerative Medicine
- Neurogenetic and Muscular Disorders Research
- Cardiac Structural Anomalies and Repair
- Gastric Cancer Management and Outcomes
- Calcium signaling and nucleotide metabolism
- RNA regulation and disease
- Extracellular vesicles in disease
Tokyo Medical and Dental University
2013-2024
The University of Tokyo
2020-2023
Dokkyo Medical University
2018
Yokohama Municipal Minato Red Cross Hospital
2011-2015
Saitama Red Cross Hospital
2010-2011
Red Cross Hospital
2011
Yokohama Minami Kyosai Hospital
2008-2010
Hiroshima University
2008
Abstract Our understanding of the spatiotemporal regulation cardiogenesis is hindered by difficulties in modeling this complex organ currently vitro models. Here we develop a method to generate heart organoids from mouse embryonic stem cell-derived embryoid bodies. Consecutive morphological changes proceed self-organizing manner presence laminin-entactin (LN/ET) and fibroblast growth factor 4 (FGF4), resulting organoid possesses atrium- ventricle-like parts containing cardiac muscle,...
Glycosylphosphatidylinositol (GPI), covalently attached to many eukaryotic proteins, not only acts as a membrane anchor but is also thought be sorting signal for GPI-anchored proteins that are associated with sphingolipid and sterol-enriched domains. GPI anchors contain core structure conserved among all species. The synthesized in two topologically distinct stages on the leaflets of endoplasmic reticulum (ER). Early intermediates assembled cytoplasmic side ER then flipped into lumen where...
Abstract Dilated cardiomyopathy (DCM) is a fatal heart disease characterized by left ventricular dilatation and cardiac dysfunction. Recent genetic studies on DCM have identified causative mutations in over 60 genes, including RBM20 , which encodes regulator of heart-specific splicing. patients with been reported to present more severe phenotypes, impaired function, atrial fibrillation (AF), arrhythmias leading sudden death, compared those the other genes. An RSRSP stretch RBM20, hotspot...
Recent experimental studies have demonstrated that several microRNAs (miRNAs) expressed in atrial tissue promote a substrate of fibrillation (AF). However, because it has not been fully elucidated whether these data contribute to identifying circulating miRNAs as biomarkers for AF, we used combined analysis human serum and murine samples with the aim predicting AF.Methods Results:Comprehensive analyses were performed screen 733 from 10 AF patients 5 controls, 672 6 inducible tachycardia...
Abstract The approval of splice-switching oligonucleotides with phosphorodiamidate morpholino oligomers (PMOs) for treating Duchenne muscular dystrophy (DMD) has advanced the field oligonucleotide therapy. Despite this progress, PMOs encounter challenges such as poor tissue uptake, particularly in heart, diaphragm, and central nervous system (CNS), thereby affecting patient’s prognosis quality life. To address these limitations, we have developed a PMOs-based heteroduplex (HDO) technology....
Background: Few studies have explored risk stratification of arrhythmic events in patients with ischemic heart diseases according to T-wave alternans (TWA) using modified moving average (MMA) method and rate turbulence (HRT). Methods Results: A retrospective analysis 63 who underwent MMA-based TWA HRT divided the into 3 groups: group-C 21 controls, group-O old myocardial infarction (OMI) showing no episodes sustained ventricular tachyarrhythmia (SVT), group-V OMI SVT received an implantable...
The administration of anthracycline drugs induces progressive and dose-related cardiac damage through several cytotoxic mechanisms, including endoplasmic reticulum (ER) stress. unfolded protein response plays a crucial role for mitigating misfolded accumulation induced by excessive ER stress.We aimed to clarify whether reticulum-selective autophagy machinery (ER-phagy) serves as an alternative system protect cardiomyocytes from stress caused drugs.Primary cultured cardiomyocytes, H9c2 cell...
Drug-induced bradycardia is common during antiarrhythmic therapy; the major culprits are beta-blockers. However, whether other drugs also a significant cause of this, alone or in combination with beta-blockers, not well known.We retrospectively investigated records all patients hospitalized at our institution for drug-related from years 2004 to 2012. Patients cardiac disease and electrolytic hormonal abnormalities that could bradyarrhythmias were excluded.Eight identified (mean age, 79±5...
Abstract Systemic inflammation is assumed to be the consequence and cause of atrial fibrillation (AF); however, underlying mechanism remains unclear. We aimed evaluate level cell-free DNA (cfDNA) in patients with AF mimicking models, illuminate its impact on inflammation. Peripheral blood was obtained from 54 104 non-AF controls, cfDNA extracted. extracted total conditioned medium after rapid pacing HL-1 cells. Nuclear mitochondrial were separately fragmented simulate nuclear-cfDNA (n-cfDNA)...
Background Sacubitril/valsartan (SacVal) has been shown to improve the prognosis of heart failure; however, whether SacVal reduces occurrence atrial fibrillation (AF) in failure not yet elucidated. In this study, we aimed determine is effective reducing AF and identify underlying mechanism its electrophysiological effect mice. Methods Adult male mice underwent transverse aortic constriction, followed by SacVal, valsartan, or vehicle treatment for two weeks. Electrophysiological study (EPS)...
Abstract Manipulating lymphocyte functions with gene silencing approaches is promising for treating autoimmunity, inflammation, and cancer. Although oligonucleotide therapy has been proven to be successful in several conditions, efficient vivo delivery of populations remains a challenge. Here, we demonstrate that intravenous injection heteroduplex (HDO), comprised an antisense (ASO) its complementary RNA conjugated α-tocopherol, silences endogenous expression higher potency, efficacy, longer...
Abstract RBM20 is one of the genes predisposing to dilated cardiomyopathy (DCM). Variants in RS domain have been reported many DCM patients, but pathogenicity variants within RNA-recognition motif remains unknown. Two human patients with I536T- variant without an apparent phenotype were identified sudden death cohorts. A splicing reporter assay was performed, and I538T knock-in mouse model ( Rbm20 ) generated determine significance this variant. The demonstrated that I536T affected TTN...
Neuropathic pain, a heterogeneous condition, affects 7%-10% of the general population. To date, efficacious and safe therapeutic approaches remain limited. Antisense oligonucleotide (ASO) therapy has opened door to treat spinal muscular atrophy, with many ongoing clinical studies determining its utility. ASO for neuropathic pain peripheral nerve disease requires efficient gene delivery knockdown in both dorsal root ganglion (DRG) sciatic nerve, key tissues signaling. We previously developed...
Recent genome-wide association studies targeting atrial fibrillation (AF) have indicated a strong between the genotype and electrophysiological phenotype in atria. That encourages us to utilize genetically-engineered mouse model elucidate mechanism of AF. However, it is difficult evaluate properties murine atria due their small size. This protocol describes evaluation using an optical mapping system with high temporal spatial resolution Langendorff perfused hearts. The assembled dual...
Abstract Background Ventricular fibrillation (VF) in Brugada syndrome (BrS) is known to occur more frequently during nighttime and from spring early summer. In this study, we investigated whether repolarization (ERS) has the same seasonal, weekly, circadian distribution of VF events as BrS using data “J‐wave associated with prior cardiac event” (J‐PREVENT) registry. Methods The study included 90 consecutive patients 31 ERS a mean follow‐up 49±37 months. Follow‐up implantable...
Calcium antagonists, nicorandil and long-acting nitrates are highly effective for preventing coronary spasm. The withdrawal of vasodilators, especially calcium is risky in cases vasospastic angina. We herein present a case cardiopulmonary arrest that occurred due to spasm triggered by the discontinuation vasodilators during peri-operative period gastrectomy. Vasospastic angina patients who not able take oral should be maintained on parenteral vasodilator until they them orally. Physicians...
Background:The purpose of this study was to clarify the relation between atrial defibrillation threshold (ADFT) for internal cardioversion (IC) and arrhythmogenicity superior vena cava (SVC).Methods Results:A total 159 consecutive patients (139 male, age 59.9±10.3 years) who underwent radiofrequency catheter ablation fibrillation (AF) were assessed. IC performed in 50 with non-long-standing persistent AF (non-LSAF) a purpose-built which direct current is delivered right atrium coronary...