A5017902899- Protein Kinase Regulation and GTPase Signaling
- Cardiovascular Function and Risk Factors
- Hormonal Regulation and Hypertension
- Cardiac Fibrosis and Remodeling
- Adipose Tissue and Metabolism
- Coronary Interventions and Diagnostics
- Cardiomyopathy and Myosin Studies
- Cardiac Arrhythmias and Treatments
- Signaling Pathways in Disease
- Heart Failure Treatment and Management
- Muscle Physiology and Disorders
- Peptidase Inhibition and Analysis
- Receptor Mechanisms and Signaling
- Nitric Oxide and Endothelin Effects
- Cardiac Imaging and Diagnostics
- Angiogenesis and VEGF in Cancer
- Protease and Inhibitor Mechanisms
- Cardiac electrophysiology and arrhythmias
- Extracellular vesicles in disease
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiac pacing and defibrillation studies
- Atrial Fibrillation Management and Outcomes
- Hippo pathway signaling and YAP/TAZ
- Mesenchymal stem cell research
- Cell Adhesion Molecules Research
Nagoya University
2016-2025
Asahi University
2017
Mizuho (Japan)
2017
Max Planck Institute for Heart and Lung Research
2012-2016
Indiana University – Purdue University Indianapolis
2016
Indiana University School of Medicine
2016
Goethe University Frankfurt
2016
Kerckhoff Klinik
2016
Max Planck Society
2013
Heidelberg University
2012
Rationale: Activated cardiac fibroblasts (CF) are crucial players in the damage response; excess fibrosis, however, may result myocardial stiffening and heart failure development. Inhibition of activated CF has been suggested as a therapeutic strategy disease, but whether this truly improves function is unclear. Objective: To study effect ablation on remodeling. Methods Results: We characterized subgroups murine by single-cell expression analysis identified periostin marker showing highest...
Cardiomyocytes are susceptible to apoptosis caused by hypoxia during the acute and subacute phases of myocardial infarction (MI). Angiogenesis can reduce MI-induced damage mitigating hypoxia. It has been speculated that ischemic border zone is a unique area rescued angiogenic therapy. However, mechanism timing for new vessel formation in mammalian heart following unclear. Identifying targets benefit from angiogenesis treatment indispensable development revolutionary therapies. Here, we...
Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication that the potential to improve cardiac function when used in cell-based therapy. However, means by which cardiomyocytes respond EVs remains unclear. Here, we sought clarify role exosomes improving investigating effect cardiomyocyte endocytosis from mesenchymal stem cells on acute myocardial infarction (MI). Exposing culture supernatant adipose-derived regenerative (ADRCs) prevented cell damage under...
To maintain and restore skeletal muscle mass function is essential for healthy aging. We have found that myonectin acts as a cardioprotective myokine. Here, we investigate the effect of on atrophy in various male mouse models dysfunction. Disruption exacerbates age-associated, sciatic denervation-induced or dexamethasone (DEX)-induced models. Myonectin deficiency also contributes to exacerbated mitochondrial dysfunction reduces expression biogenesis-associated genes including PGC1α...
Myofibroblasts have roles in tissue repair following damage associated with ischemia, aging, and inflammation also promote fibrosis stiffening, causing organ dysfunction. One source of myofibroblasts is mesenchymal stromal/stem cells that exist as resident fibroblasts multiple tissues. We previously identified meflin (mesenchymal stromal cell- fibroblast-expressing Linx paralogue), a glycosylphosphatidylinositol-anchored membrane protein, specific marker regulator their undifferentiated...
Cardiac remodeling in response to pressure or volume overload plays an important role the pathogenesis of heart failure. Various mechanisms have been suggested translate mechanical stress into structural changes, one them being release humoral factors such as angiotensin II and endothelin-1, which turn promote cardiac hypertrophy fibrosis. A large body evidence suggests that prohypertrophic effects these are mediated by receptors coupled G(q/11) family heterotrimeric G proteins. Most...
Arterial hypertension is a major risk factor for cardiovascular diseases. The kidney and its natriuretic function are in the centre of prevailing models to explain pathogenesis hypertension; however, mechanisms underlying blood pressure elevation remain unclear most patients. Development strongly correlated with age, this increase typically accelerates fourth decade life. cause age-dependent poorly understood. This study aims understand role procontractile G-protein-mediated signalling...
Secreted factors produced by adipose tissue are involved in the pathogenesis of cardiovascular disease. We previously identified adipolin, also known as C1q/TNF-related protein 12, an insulin-sensitizing adipokine. However, role adipolin vascular disease remains unknown. Here, we investigated whether modulates pathological remodelling.Adipolin-knockout (APL-KO) and wild-type (WT) mice were subjected to wire-induced injury femoral artery. APL-KO showed increased neointimal thickening after...
Abstract Chronic kidney disease is a life‐threatening worldwide. PPARα crucial transcriptional regulator of lipid metabolism and inflammation. Here, we examine whether novel selective modulator, pemafibrate modulates renal injury in model unilateral ureteral obstruction (UUO). Administration to wild‐type (WT) mice led reduction dysfunction fibrosis after UUO with accompanying increases plasma levels fibroblast growth factor (FGF) 21 ketone body β‐hydroxybutyrate (BHB). Treatment WT FGF21 or...
Despite the efficacy of many therapies for heart failure, it remains a leading cause morbidity and mortality worldwide, with patients progressing to advanced stages condition. Since standard treatment failure includes small-molecule drugs targeting G protein-coupled receptors (GPCRs), GPCRs are still considered novel targets diagnosis cardiovascular diseases. Corticotropin-releasing hormone receptor 2, highly expressed GPCR in cardiomyocytes, its ligand, urocortin2 (UCN2), have been...
Cell migration is important in the development of atherosclerotic lesions. Macrophages and smooth muscle cells migrate into subendothelial space arteries, leading to plaque formation. Long‐term inhibition activity Rho‐kinase induces a regression coronary lesions, probably by preventing macrophages cells. Previous reports concerning effect inhibitors on cell are contradictory, however. We examined here type specificity found that endothelial cells, macrophages, was inhibited treatment with...
RhoA is transiently activated by specific extracellular signals such as endothelin-1 (ET-1) in vascular smooth muscle cells. RhoGAP negatively regulates activity: thus, becomes the GDP-bound inactive form afterward. Sustained activation of induced with high doses and implicated certain diseases vasospasms. However, it remains largely unknown how prolonged induced. Here we show that Rho-kinase, an effector RhoA, phosphorylated p190A at Ser1150 attenuated activity COS7 Binding Rnd to thought...
Heart failure is a complex syndrome that results from structural or functional impairment of ventricular filling blood ejection. Protein phosphorylation major and essential intracellular mechanism mediates various cellular processes in cardiomyocytes response to extracellular signals. The RHOA-associated protein kinase (ROCK/Rho-kinase), an effector regulated by the small GTPase RHOA, causes pathological proteins, resulting cardiovascular diseases. RHOA also activates N (PKN); however, role...
After binding of epidermal growth factor (EGF), the EGF receptor is activated, internalized by endocytosis, and subsequently degraded in lysosomal pathway. Endocytotic trafficking activated essential for controlling signaling. Upon ligand‐induced activation receptors, Cbl (ubiquitin ligase) binds to leads translocation CIN85 (Cbl‐interacting protein 85 kDa)/endophilin complex vicinity receptors. Endophilin known as a key regulator clathrin‐mediated endophilin active thought promote...
Structural cardiac remodeling, including hypertrophy and fibrosis, plays a crucial role in the pathogenesis of heart failure. In vitro studies suggested small GTPase RhoA hypertrophic cardiomyocyte growth, but neither molecular mechanisms leading to activation nor their relevance vivo are known. We use here mass spectrometric approach identify Rho guanine nucleotide exchange factors (RhoGEFs) activated during pressure overload show that RhoGEF12 is central player remodeling. required for...
Heart failure occurs when the heart is unable to effectively pump blood and maintain tissue perfusion. Despite numerous therapeutic advancements over previous decades, prognosis of patients with chronic remains poor, emphasizing need identify additional pathophysiological factors. Here, we show that corticotropin releasing hormone receptor 2 (Crhr2) a G protein-coupled highly expressed in cardiomyocytes continuous infusion Crhr2 agonist, urocortin (Ucn2), reduced left ventricular ejection...
Vascular smooth muscle (Sm) cells (VSMCs) are highly plastic. Their differentiation state can be regulated by serum response factor (SRF), which activates genes involved in Sm and proliferation recruiting cofactors, such as members of the myocardin family ternary complex factors (TCFs), respectively. However, extracellular cues upstream signaling mechanisms regulating SRF-dependent VSMC under vivo conditions poorly understood. In this study, we show that procontractile pathways mediated G...
In the heart, fatty acid is a major energy substrate to fuel contraction under aerobic conditions. Ischemia downregulates metabolism adapt limited oxygen supply, making glucose preferred substrate. However, mechanism underlying myocardial metabolic shift during ischemia remains unknown. Here, we show that lipoprotein lipase (LPL) expression in cardiomyocytes, principal enzyme converts triglycerides free acids and glycerol, increases infarction (MI). Cardiomyocyte-specific LPL deficiency...
Background Circadian rhythm disorders, often seen in modern lifestyles, are a major social health concern. The aim of this study was to examine whether circadian disorders would influence angiogenesis and blood perfusion recovery mouse model hind limb ischemia. Methods Results A jet-lag established C57BL/6J mice using light-controlled isolation box. Control were kept at light/dark 12:12 (12-hour light 12-hour dark) condition. Concentrations plasma vascular endothelial growth factor...
Abstract Mesenchymal stem cells (MSCs) are the likely precursors of multiple lines mesenchymal cells. The existence bona fide MSCs with self‐renewal capacity and differentiation potential into all lineages, however, has been unclear because lack MSC‐specific marker(s) that not expressed by terminally differentiated progeny. Meflin, a glycosylphosphatidylinositol‐anchored protein, is an MSC marker candidate specifically in rare stromal tissues. Our previous report showed Meflin expression...
Abstract Identifying specific markers of adipose stem and progenitor cells (ASPCs) in vivo is crucial for understanding the biology white tissues (WAT). PDGFRα‐positive perivascular stromal represent best candidates ASPCs. This cell lineage differentiates into myofibroblasts that contribute to impairment WAT function. However, ASPC marker protein(s) are functionally maintaining homeostasis unknown. We previously identified Meflin as a mesenchymal (MSCs) bone marrow tissue‐resident...