A5084358563- Cardiovascular Function and Risk Factors
- Adipose Tissue and Metabolism
- Diabetes Treatment and Management
- Peptidase Inhibition and Analysis
- Neuropeptides and Animal Physiology
- Cancer, Hypoxia, and Metabolism
- Cardiovascular Effects of Exercise
- Sirtuins and Resveratrol in Medicine
- Mitochondrial Function and Pathology
- Hormonal Regulation and Hypertension
- Cardiac Fibrosis and Remodeling
- Signaling Pathways in Disease
- Cardiomyopathy and Myosin Studies
- Cardiac electrophysiology and arrhythmias
- Coronary Interventions and Diagnostics
- Cardiac and Coronary Surgery Techniques
- Cardiovascular Disease and Adiposity
- Receptor Mechanisms and Signaling
- Cardiac, Anesthesia and Surgical Outcomes
- Apelin-related biomedical research
- Chemokine receptors and signaling
- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Monoclonal and Polyclonal Antibodies Research
- Metabolomics and Mass Spectrometry Studies
Max Planck Institute for Heart and Lung Research
2023-2025
Nagoya University
2001-2024
Okayama University Hospital
2013
Okazaki City Hospital
2009-2011
Tokyo Institute of Technology
1996
Insulin resistance is a hallmark of obesity-associated type 2 diabetes. Insulin’s actions go beyond metabolic cells and also involve blood vessels, where insulin increases capillary flow delivery nutrients. We show that adrenomedullin, whose plasma levels are increased in obese humans mice, inhibited signaling human endothelial through protein-tyrosine phosphatase 1B–mediated dephosphorylation the receptor. In mice lacking adrenomedullin receptor, insulin-induced nitric oxide–synthase...
Abstract Activation of endothelial YAP/TAZ signaling is crucial for physiological and pathological angiogenesis. The mechanisms regulation are, however, incompletely understood. Here we report that the protocadherin FAT1 acts as a critical upstream regulator which limits activity these transcriptional cofactors during developmental tumor angiogenesis by promoting their degradation. We show loss results in increased cell proliferation vitro various models vivo. This effect due to perturbed...
Macrophages express numerous G protein-coupled receptors (GPCRs) that regulate adhesion, migration, and activation, but the function of orphan receptor GPRC5B in macrophages is unknown. Both resident peritoneal bone marrow-derived from myeloid-specific GPRC5B-deficient mice show increased migration phagocytosis, resulting improved bacterial clearance a peritonitis model. In other models such as myocardial infarction, myeloid cell recruitment has adverse effects. Mechanistically, we found...
Background— Ample evidence demonstrates cardiovascular protection by incretin-based therapy using dipeptidyl peptidase 4 inhibitor (DPP4i) and glucagon-like peptide-1 (GLP-1) under either diabetic or nondiabetic condition. Their action on myocardium is mediated the cyclic AMP (cAMP) signal; however, pathway remains uncertain. This study was conducted to address effect of DPP4i/GLP-1/cAMP axis cardiac dysfunction remodeling induced pressure overload (thoracic aortic constriction [TAC])...
Aims: Alcohol dehydrogenase β subunit (ADH2) Arg47His and aldehyde 2 (ALDH2) Glu487Lys were genotyped by a duplex polymerase chain reaction (PCR) with confronting two-pair primers (PCR–CTPP), which allows DNA amplification one-tube PCR including eight primers, subsequent electrophoresis. Methods: Several conditions tested to establish the optimal for distinguishing allele-specific bands two polymorphisms. Under conditions, 454 Japanese health check-up examinees genotyped. Results: The...
Atypical chemokine receptors (ACKRs) play pivotal roles in immune regulation by binding chemokines and regulating their spatial distribution without inducing G-protein activation. Recently, GPR182, provisionally named ACKR5, was identified as a novel ACKR expressed microvascular lymphatic endothelial cells, with functions hematopoietic stem cell homeostasis. Here, we comprehensively investigated the profile of human mouse GPR182. Competitive assays using flow cytometry revealed that besides...
Vascular smooth muscle cells (VSMCs) are highly plastic. Vessel injury induces a phenotypic transformation from differentiated to dedifferentiated VSMCs, which involves reduced expression of contractile proteins and increased production extracellular matrix inflammatory cytokines. This transition plays an important role in several cardiovascular diseases such as atherosclerosis, hypertension, aortic aneurysm. TGF-β (transforming growth factor-β) is critical for VSMC differentiation...
Chronic fibrotic tissue disrupts various organ functions. Despite significant advances in therapies, mortality and morbidity due to heart failure remain high, resulting poor quality of life. Beyond the cardiomyocyte-centric view failure, it is now accepted that alterations interstitial extracellular matrix (ECM) also play a major role development failure. Here, we show protein kinase N (PKN) expressed cardiac fibroblasts. Furthermore, PKN mediates conversion fibroblasts into myofibroblasts,...
We have developed a simple method to purify sequence-specific DNA-binding proteins directly from crude cell extracts by using DNA affinity latex beads. The enabled us not only proteins, but also their associated proteins. Using beads bearing the ATF/E4TF3 site adenovirus E4 gene promoter, protein kinase activity was copurified with family. found that interacted ATF1 in vitro efficiently. did bind DNA. mainly phosphorylated on serine 36, which one of target amino acids for casein (CK) II....
The force-frequency relation (FFR) is a hemodynamic index of the chronotropic relationship between left ventricular (LV) systolic function (percent change in dP/dtmax) and elevation heart rate. FFR marker myocardial contractile reserve follows an upward slope healthy myocardium [monophasic (MoF)], pattern that becomes biphasic (BiF) under pathological conditions. However, it remains uncertain whether determines patient's prognosis. We investigated promising role as predictor cardiac events...
Protein phosphorylation, controlled by protein kinases, is central to regulating various pathophysiological processes, including cardiac systolic function. The dysregulation of kinase activity plays a significant role in the pathogenesis dysfunction. While contraction mechanisms are well documented, underlying diastole remain elusive. This gap persists owing historical focus on dysfunction heart failure research. Recently, with preserved ejection fraction (HFpEF), an age-related disease...
Abstract Background Amyloid precursor protein (APP) gives rise to amyloid-β peptides and thus has a key role in the pathogenesis of Alzheimer´s disease. APP is also highly expressed outside brain including cells cardiovascular system, particular endothelial (1). However, its proteolytic fragments function disease remains unknown. Purpose The main purpose this study was understand close homologue, amyloid precursor-like 2 (APLP2) cells. Methods To test potential APLP2 vivo, we generated...
Introduction: Aging causes skeletal muscle atrophy (i.e. sarcopenia). In heart, aging is also known to cause cardiac dysfunction such as diastolic dysfunction; however, the impact of on myocardial cell growth remains uncertain. Hypothesis: Because pivotal role protein kinase Akt in cellular and cardiomyocytes, we hypothesized whether #1 may impairs activation leading aged heart #2 regular exercise enhance activity, augmentation cardiomyocyte that results reversal aging-mediated atrophy....
Aim: The purpose of this study is to screen the target metabolites diabetic microangiopathy in heart by use whole metabolome analysis. Methods: Diet-induced type 2 mouse were divided into two groups; control and those treated with remedy GLP-1 receptor agonist Ex-4 for 5 weeks. Mice euthanized analyzed at age 16 week-old. Results: capillary density T2DM was reduced as compared non-diabetic counterparts, which restored Ex4 treatment. Changes angiogenic signals detected immunoblotting analysis...
RATIONALE: Sirtuin 3 (SIRT3) is a mitochondrial protein deacetylase that maintains basal ATP yield and its expression level increased by fasting, exercise, some NAD+ intermediates. We recently reported the glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 (Ex-4) ameliorated cardiac remodeling in diabetic cardiomyopathy via increase cyclic AMP (AJP2013). Because changes regulated adenylyl cyclase which one of downstream target Ex-4, we hypothesized SIRT3 may involve Ex-4-mediated...
Purpose: Aging is one of the primary factors causing left-ventricular (LV) remodeling and susceptibility to heart failure (HF). Clinical evidences demonstrate a sustained exercise (EX) ameliorates HF; however, molecular mechanism underlying aging-related LV remains uncertain few data have demonstrated whether EX may be beneficial for contractility. Because preclinical studies indicate pivotal role protein kinase Akt in aging, we thus hypothesized exert benefits on HF induced by aging which...
Introduction: Hypertension is primary cause of heart failure (HF). Several reports demonstrated the blood-pressure (BP)-lowering property dipeptidyl peptidase 4 (DPP4) inhibitors. Hypothesis: We tested effect a new DPP4 inhibitor teneligliptin on BP and HF using preclinical models. Methods: Spontaneously hypertensive rats (SHR; 10 week-old male) normotensive counterpart (WKY) were treated with TEN (10mg/kg/day) for weeks. Hypertensive was evaluated in terms BP, cardiac function, histological...