A5102866064- Cardiac Ischemia and Reperfusion
- Cardiac electrophysiology and arrhythmias
- Cardiomyopathy and Myosin Studies
- Cardiovascular Function and Risk Factors
- Nitric Oxide and Endothelin Effects
- Cardiac Fibrosis and Remodeling
- Metabolism, Diabetes, and Cancer
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- Cardiac Arrest and Resuscitation
- Heart Failure Treatment and Management
- Signaling Pathways in Disease
- Cardiac Imaging and Diagnostics
- Adenosine and Purinergic Signaling
- Congenital heart defects research
- Endoplasmic Reticulum Stress and Disease
- Angiogenesis and VEGF in Cancer
- Receptor Mechanisms and Signaling
- Anesthesia and Neurotoxicity Research
- Cell Adhesion Molecules Research
- Renin-Angiotensin System Studies
- Mechanical Circulatory Support Devices
- Cardiovascular Effects of Exercise
- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
Osaka University
2016-2025
Ube Frontier University
2020-2024
Medical Research Foundation
2024
Teijin (Japan)
2006-2023
Hyogo University
2023
Japan Science and Technology Agency
2015-2020
Osaka Medical and Pharmaceutical University
2016
National Cerebral and Cardiovascular Center
2003-2014
Toyohashi Heart Center
2010
Southern Medical University
2010
Background Moyamoya disease is an idiopathic vascular disorder of intracranial arteries. Its susceptibility locus has been mapped to 17q25.3 in Japanese families, but the gene unknown. Methodology/Principal Findings Genome-wide linkage analysis eight three-generation families with moyamoya revealed (P<10-4). Fine mapping demonstrated a 1.5-Mb bounded by D17S1806 and rs2280147. We conducted exome index cases these results filtered through Ng criteria. There was variant p.N321S PCMTD1 p.R4810K...
The endoplasmic reticulum (ER) is recognized as an organelle that participates in folding secretory and membrane proteins. ER responds to stress by upregulating chaperones, but prolonged and/or excess leads apoptosis. However, the potential role of pathophysiological hearts remains unclear.Mice were subjected transverse aortic constriction (TAC) or sham operation. Echocardiographic analysis demonstrated mice 1 4 weeks after TAC had cardiac hypertrophy failure, respectively. Cardiac...
Apoptosis may contribute to the development of heart failure, but role apoptotic signaling initiated by endoplasmic reticulum in this condition has not been well clarified.In myocardial samples from patients with quantitative real-time polymerase chain reaction revealed an increase messenger RNA for C/EBP homologous protein (CHOP), a transcriptional factor that mediates reticulum-initiated cell death. We performed transverse aortic constriction or sham operation on wild-type (WT) and...
Neuropilins (NP1 and NP2) are vascular endothelial growth factor (VEGF) receptors that mediate developmental tumor angiogenesis. Transgenic mice, in which both NP1 NP2 were targeted −/− ) died utero at E8.5. Their yolk sacs totally avascular. Mice deficient for but heterozygous +/− or also embryonic lethal survived to E10–E10.5. The E10 embryos easier analyze phenotype than the fragile poorly formed 8.5 embryos. phenotypes of these mice very abnormal. sacs, although normal size, lacked...
The heparin-binding epidermal growth factor (EGF)-like (HB-EGF) is a member of the EGF family factors that binds to and activates receptor (EGFR) related tyrosine kinase, ErbB4. HB-EGF-null mice (HB del/del ) were generated examine role HB-EGF in vivo . More than half HB died first postnatal week. survivors developed severe heart failure with grossly enlarged ventricular chambers. Echocardiographic examination showed chambers dilated cardiac function was diminished. Moreover, valves. valve...
Objective: Insulin resistance (IR) was reported to be associated with chronic heart failure (CHF). Adiponectin, an insulin-sensitizing hormone anti-inflammatory activity, improves energy metabolism via AMP-activated protein kinase (AMPK). AMPK deficiency is depressed cardiac function under stress conditions. However, it not clear whether adiponectin plays important role in CHF. We hypothesize that of might result deterioration failure.
BACKGROUND Adenosine has been reported to mediate the necrosis-limiting effects of ischemic preconditioning; however, it is unclear how this mediation occurs. The present study was undertaken test hypothesis that preconditioning increases 5'-nucleotidase activity and adenosine release during sustained ischemia subsequent reperfusion. METHODS AND RESULTS After thoracotomy, left anterior descending coronary artery cannulated perfused with blood redirected from carotid in 32 dogs. Ischemic...
Marked sarcomere disorganization is a well-documented characteristic of cardiomyocytes in the failing human myocardium. Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC2v), which involved development cardiomyopathy, an important structural protein that affects physiologic cardiac formation and heart development. Integrated cDNA expression analysis myocardia uncovered novel kinase, cardiac-specific myosin kinase (cardiac-MLCK), acts on MLC2v. Expression levels...
Although AMPK plays well-established roles in the modulation of energy balance, recent studies have shown that activation has potent anti-inflammatory effects. In present experiments, we examined role phagocytosis. We found ingestion Escherichia coli or apoptotic cells by macrophages increased activity. ability neutrophils to ingest bacteria (by 46±7.8 85±26%, respectively, compared control, P<0.05) and 21±1.4%, P<0.05 control). resulted cytoskeletal reorganization, including enhanced...
Dilated cardiomyopathy (DCM) and hypertrophic (HCM) are genetically phenotypically heterogeneous. Cardiac function is improved after treatment in some patients, but little known about genetic predictors of long-term outcomes myocardial recovery following medical treatment. To elucidate the basis Japan genotypes involved prognosis left ventricular reverse remodeling (LVRR), we performed targeted sequencing on 120 DCM (70 sporadic 50 familial) 52 HCM (15 37 patients integrated their with...
Foxp3+ regulatory T (Treg) cells, which suppress immune responses, are highly proliferative in vivo. However, it remains unclear how the active replication of Treg cells is maintained Here, we show that branched-chain amino acids (BCAAs), including isoleucine, required for maintenance state via acid transporter Slc3a2-dependent metabolic reprogramming. Mice fed BCAA-reduced diets showed decreased numbers with defective vivo capacity. lacking Slc3a2 specifically impaired and cells....
Significance We identified hypoxia-inducible domain family, member 1A (Higd1a) as a positive regulator of cytochrome c oxidase (CcO). CcO, the terminal component mitochondrial electron transfer system, reductively converts molecular oxygen to water coupled pump protons across inner membrane. Higd1a is transiently induced under hypoxic conditions and increases CcO activity by directly interacting with in vicinity its active center. Induction leads increased consumption subsequent ATP...
Heparin-binding EGF-like growth factor (HB-EGF) is first synthesized as a membrane-anchored form (proHB-EGF), and its soluble (sHB-EGF) released by ectodomain shedding from proHB-EGF. To examine the significance of proHB-EGF processing in vivo, we generated mutant mice targeted gene replacement, expressing either an uncleavable (HBuc) or transmembrane domain–truncated (HBΔtm) molecule. HBuc/uc developed severe heart failure enlarged valves, phenotypes similar to those null mice. On other...
BACKGROUND We have previously reported that ischemic preconditioning increases 5'-nucleotidase activity and adenosine release during ischemia reperfusion. However, its direct cause-and-effect relation has not been proven. To test the idea infarct size-limiting effect of is blunted by inhibition ectosolic activity, we assessed release, size caused sustained with without an exposure to alpha,beta,-methylene 5'-diphosphate (AOPCP) in ischemia-preconditioned myocardium. METHODS AND RESULTS In 67...
Proteasome inhibitors are a novel class of anticancer agents that induce tumour cell death via endoplasmic reticulum (ER) stress. Since ER stress is involved in the development heart failure, we investigated role ER-initiated cardiomyocyte by proteasome inhibition.Rat neonatal cardiomyocytes were used this study. activity was assayed using peptidase substrates. Cell viability and apoptosis measured 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenol tetrazolium bromide flow cytometry, respectively....
We characterized the time course of left ventricular (LV) geometric and functional changes after aortic banding, validated them by necropsy, investigated sensitivity echocardiographic findings on LV hypertrophy. C57BL/6 mice were subjected to transverse constriction (TAC) or sham operation; assessments performed before at 2, 4, 6, 11 wk surgery; some euthanized corresponding points. There was a progressive increase in diastolic posterior wall thickness systolic dimension; percentage...