- Cardiovascular Function and Risk Factors
- Cardiac Structural Anomalies and Repair
- Cardiac electrophysiology and arrhythmias
- Cardiac Valve Diseases and Treatments
- Pulmonary Hypertension Research and Treatments
- Cardiac Imaging and Diagnostics
- Mechanical Circulatory Support Devices
- Organ Transplantation Techniques and Outcomes
- Phosphodiesterase function and regulation
- Cardiac Ischemia and Reperfusion
- Cardiovascular Issues in Pregnancy
- Cardiac Arrest and Resuscitation
- Heart Failure Treatment and Management
- Congenital Heart Disease Studies
- Receptor Mechanisms and Signaling
- Cardiovascular Disease and Adiposity
- Bone Metabolism and Diseases
- Mitochondrial Function and Pathology
- Adenosine and Purinergic Signaling
- Immune Response and Inflammation
- Liver Disease and Transplantation
- Bone and Dental Protein Studies
- S100 Proteins and Annexins
- Cardiac Fibrosis and Remodeling
- Coronary Interventions and Diagnostics
University of Tokyo Hospital
2008-2025
The University of Tokyo
2011-2024
Icahn School of Medicine at Mount Sinai
2019-2024
Johns Hopkins Medicine
2019-2024
Johns Hopkins University
2019-2024
Tokyo Medical University
2020
Kariya City Board of Education
2012-2019
Nihon University
2012-2017
Tokyo Metropolitan Geriatric Hospital
2017
Dokkyo Medical University
2016
Experimental evidence has clarified distant organ dysfunctions induced by AKI. Crosstalk between the kidney and heart, which been recognized recently as cardiorenal syndrome, appears to have an important role in clinical settings, but mechanisms AKI causes cardiac injury remain poorly understood. Both heart are highly energy-demanding organs that rich mitochondria. Therefore, we investigated of mitochondrial dynamics kidney–heart crosstalk. Renal ischemia reperfusion (IR) was bilateral renal...
Low‐intensity pulsed ultrasound (LIPUS) is used for bone healing in orthopedics and dentistry. It has been shown that LIPUS induces the secretion of extracellular adenosine triphosphate (ATP), a key mediator osteoblast response to mechanical stimuli. However, detailed mechanism LIPUS‐induced osteogenesis elusive. In this study, we investigated role P2X7 receptor osteogenesis. induced release ATP, differentiation osteoblasts via receptor, without affecting activity alkaline phosphatase...
Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Acute mechanical left ventricular (LV) support has been suggested to improve perfusion. However, its regulatory mechanism remains unclear. We investigated the physiological mechanisms in six Yorkshire pigs, which were subjected 90-min balloon occlusion of anterior descending artery. During acute reperfusion phase, LV using an Impella heart pump was initiated. pressure, coronary flow and pressure artery...
Pharmacologic beta-blockade is a well-established therapy for reducing adverse effects from sympathetic overactivity in cardiovascular diseases, such as heart failure. Despite decades of research efforts, vivo cardiac functional studies utilizing genetic animal models remain scant. We generated mouse model cardiomyocyte-specific deletion beta-1 adrenergic receptor (ADRB1) , the primary subtype expressed myocytes, and demonstrated role ADRB1 maintenance function at baseline during exposure to...
Tobacco smoking is an important risk factor for the development of several cancers, osteoporosis, and inflammatory diseases such as periodontitis. Nicotine one major components tobacco. In previous study, we showed that nicotine inhibits mineralized nodule formation by osteoblasts, culture medium from osteoblasts containing lipopolysaccharide increases osteoclast differentiation. However, direct effect on differentiation function osteoclasts poorly understood. Thus, examined effects...
The currently proposed criteria for identifying patients who would benefit from cardiac resynchronization therapy (CRT) still need to be optimized. A multi-scale heart simulation capable of reproducing the electrophysiology and mechanics a beating may help resolve this problem. objective retrospective study was test capability patient-specific models reproduce response CRT by applying latest technology.We created with realistic three-dimensional morphology based on clinical data recorded...
Krüppel-like factors (KLFs) are a family of transcription which play important roles in the heart under pathological and developmental conditions. We previously identified cloned Klf6 whose homozygous mutation mice results embryonic lethality suggesting role cardiovascular development. Effects KLF6 on regulation were investigated present study. Mice heterozygous for resulted significantly diminished levels cardiac fibrosis response to angiotensin II infusion. Intriguingly, similar phenotype...
Using genetically engineered mice lacking estrogen receptor-α non-nuclear signaling, this study demonstrated that receptor−α signaling activated myocardial cyclic guanosine monophosphate-dependent protein kinase G and conferred protection against cardiac remodeling induced by pressure overload. This pathway was indispensable to the therapeutic efficacy of monophosphate−phosphodiesterase 5 inhibition but not soluble guanylate cyclase stimulation. These results might partially explain...
ABSTRACT Orthodontic tooth movement induces alveolar bone resorption and formation by mechanical stimuli. Force exerted on the traction side promotes formation. Adenosine triphosphate (ATP) is one of key mediators that respond to cells However, effect tension force (TF)‐induced ATP osteogenesis inadequately understood. Accordingly, we investigated TF production in MC3T3‐E1 cells. Cells were incubated presence or absence P2X7 receptor antagonist A438079, then stimulated with without cyclic...
The heart responds to hemodynamic overload through cardiac hypertrophy and activation of the fetal gene program. However, these changes have not been thoroughly examined in individual cardiomyocytes, relation between cardiomyocyte size expression remains elusive. We established a method high-throughput single-molecule RNA imaging analysis vivo cardiomyocytes determined spatial temporal during development failure.We applied three novel single-cell methods, namely, quantitative PCR (sc-qPCR),...
Background Recent studies, supported by advances in computer science, have successfully simulated the excitation and repolarization processes of heart, based on detailed cell models electrophysiology implemented with realistic morphology . Methods In this study, we extend these approaches to simulate body surface electrocardiogram (ECG) specific individuals. Patient‐specific finite element heart torso are created for four patients various diseases, clinical data including tomography, while...
In this paper, we propose an algorithm that optimizes the ventricular fiber structure of human heart. A number histological studies and diffusion tensor magnetic resonance imaging analyses have revealed myocardial forms a right-handed helix at endocardium. However, formation changes its orientation as function transmural depth, becoming left-handed epicardium. To determine how nature can construct such structure, which obtains surprising pumping performance, introduce macroscopic modeling...
We report a mechanism that underlies stress-induced cognitive inflexibility at the molecular level. In mouse model under subacute cellular stress in which deficits rule shifting tasks were elicited, nuclear glyceraldehyde dehydrogenase (N-GAPDH) cascade was activated specifically microglia prelimbic cortex. The normalized with pharmacological intervention compound (the RR compound) selectively blocked initiation of N-GAPDH without affecting glycolytic activity. normalization also observed...
Oestrogen exerts beneficial cardiovascular effects by binding to specific receptors on various cells activate nuclear and non-nuclear actions. receptor α (ERα) signalling confers protection against heart failure remodelling, involving myocardial cyclic guanosine monophosphate (cGMP)-cGMP-dependent protein kinase G (PKG) activation; however, its tissue-specific role remains elusive. Herein, we examine the cell type-specific of ERα in oestrogen-conferred failure.
Adeno-associated virus-based gene therapy is a promising avenue in heart failure treatment, but has shown limited cardiac virus uptake humans, requiring new approaches for clinical translation. Using Yorkshire swine ischemic model, we demonstrate significant improvement with temporary coronary occlusions assisted by mechanical circulatory support. We first show that support during artery prevents hemodynamic deterioration (n = 5 female). Subsequent experiments delivery improve transduction,...
Right ventricular (RV) dysfunction following left (LV) failure is associated with poor prognosis. RV remodeling thought initiated by the increase in afterload of due to secondary pulmonary hypertension (PH) impaired LV function; however, molecular changes might occur earlier stages disease. cGMP (cyclic guanosine monophosphate)-phosphodiesterase 5 (PDE5) inhibitors, widely used treat PH through their vasorelaxation properties, have shown direct cardiac benefits, but impacts on diseases are...
Coronary microembolization is one of the main causes "no-reflow" phenomenon, which commonly occurs after reperfusion an occluded coronary artery. Given its high incidence and fact that it has been proven to be independent predictor cardiac morbidity mortality, there imperative need study underlying mechanisms pathophysiology. Large animal models are essential perform translational studies. Currently no model recapitulates a clinical scenario thrombogenic microembolism with preceding...
Sobel et al., 1 reporting the prevalence of apolipoprotein E (apoE) genotypes among Finnish centenarians, noted that presence e4 allele does not necessarily lead to Alzheimer's disease (AD) in this population and suggested relationship between apoE AD may be age-dependent. Recently, we also carried out an almost complete survey centenarians living Yamanashi prefecture, a district Japan with 0.87 million, determined …
Acute pancreatitis remains a disease of uncertain pathogenesis and no established specific therapy. Previously, we found predominant increase active proliferation macrophages in the inflamed tissues rat duct-ligation model. To analyze origin possible role these macrophages, investigated their situ cellular kinetics model using recently method multicolor immunostaining for macrophage markers proliferating cells with ethynyl deoxyuridine. detect monocyte-derived green fluorescent...
Lymphocyte recruitment into the portal tract is crucial not only for homeostatic immune surveillance but also many liver diseases. However, exact route of entry lymphocytes still obscure. We investigated this question using a rat hepatic allograft rejection model.A migration was analyzed by immunohistological methods including recently developed scanning electron microscopy method. Transmigration-associated molecules such as selectins, integrins, and chemokines their receptors expressed...