- Heart Failure Treatment and Management
- Cardiac Fibrosis and Remodeling
- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Renin-Angiotensin System Studies
- Biochemical Analysis and Sensing Techniques
- Signaling Pathways in Disease
- Diabetes Management and Research
- Hormonal Regulation and Hypertension
- Receptor Mechanisms and Signaling
- Cardiovascular Disease and Adiposity
- Cardiomyopathy and Myosin Studies
- Lipoproteins and Cardiovascular Health
- Diabetes Treatment and Management
- Nitric Oxide and Endothelin Effects
- ATP Synthase and ATPases Research
- Cardiovascular Function and Risk Factors
- Protein Kinase Regulation and GTPase Signaling
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Angiogenesis and VEGF in Cancer
- Ion Transport and Channel Regulation
- Chemotherapy-induced cardiotoxicity and mitigation
- Chronic Kidney Disease and Diabetes
- Cardiovascular Issues in Pregnancy
Toyooka Hospital
2016-2025
Kurashiki Medical Center
2025
National Cerebral and Cardiovascular Center
2009-2019
King's College London
2015
British Heart Foundation
2015
Osaka University
2015
Obihiro National Hospital
2015
Kobe City Medical Center General Hospital
2015
Tokushima University
2009-2014
National Sagamihara Hospital
2007-2011
We previously demonstrated that brain natriuretic peptide (BNP) is a cardiac hormone mainly produced in the ventricle, while major production site of atrial (ANP) atrium. To assess pathophysiological role BNP ventricular overload, we have examined gene expression BNP, In comparison with ANP, model hypertrophy using cultured neonatal rat cardiocytes. During cardiocyte evoked by endothelin-1, Phenylephrine, or PMA, steady state level mRNA increased as rapidly "immediate-early" induction c-fos...
We have established a specific radioimmunoassay (RIA) for C-type natriuretic peptide (CNP), the third member of family, and elucidated its tissue distribution molecular form. In rats, high concentrations CNP-like immunoreactivity (-LI) were detected in anterior lobe (19.8 +/- 8.6 pmol/g) neurointermediate (4.64 0.74 pituitary gland. CNP-LI was present throughout brain with hypothalamus cerebellum. Small amounts also lower part gastrointestinal tract kidney. However, no significant amount...
Guanylyl cyclase-A (NPR-A; GC-A) is the major and possibly only receptor for atrial natriuretic peptide (ANP) or B-type peptide. Although mice deficient in GC-A display an elevated blood pressure, resultant cardiac hypertrophy much greater than other mouse models of hypertension. Here we overproduce myocytes wild-type null animals. Introduction transgene did not alter pressure heart rate as a function genotype. Cardiac myocyte size was larger (approximately 20%) However, introduction reduced...
Background— Patients with PCSK9 gene gain of function (GOF) mutations have a rare form autosomal dominant hypercholesterolemia. However, data examining their clinical characteristics and geographic distribution are lacking. Furthermore, no randomized treatment study in this population has been reported. Methods Results— We compiled GOF mutation carriers multinational retrospective, cross-sectional, observational study. then performed placebo-phase, double-blind alirocumab 150 mg administered...
A recent study suggests that exogenous ghrelin administration might decrease renal sympathetic nerve activity in conscious rabbits. In the present study, we investigated whether would attenuate left ventricular (LV) remodeling following myocardial infarction (MI) via suppression of cardiac activity. Ghrelin (100 microg/kg sc, twice daily, n = 15) or saline (n were administered for 2 wk from day after MI operation Sprague-Dawley rats. The effects on evaluated by echocardiographic,...
Disruption of guanylyl cyclase-A (GC-A) results in mice displaying an elevated blood pressure, which is not altered by high or low dietary salt. However, atrial natriuretic peptide (ANP), a proposed ligand for GC-A, has been suggested as critical the maintenance normal pressure during salt intake. In this report, we show that infusion ANP substantial natriuresis and diuresis wild-type but fails to cause significant changes sodium excretion urine output GC-A-deficient mice. ANP, therefore,...
To elucidate the physiological and pathophysiological roles of natriuretic peptide family in vascular smooth muscle cells, which is implicated growth inhibition as well vasorelaxation, we have examined phenotype-related expression three kinds receptors rat aortic cells. The at mRNA level was studied by Northern blot hybridization, protein determined cGMP production method receptor binding assay. In intact media, atrial (ANP)-A ANP-B were detected, potency ANP least two orders magnitude...
Abstract Objective Tumour budding, defined as small clusters of undifferentiated cancer cells at invasive margins, has been shown to reflect biologic aggressiveness colorectal cancers. We therefore examined the prognostic significance tumour budding in patients with carcinoma, particularly focusing on comparisons other clinicopathological findings. Method was investigated surgically resected specimens from 159 carcinoma. With haematoxylin and eosin stained slides containing entire margin,...
Mice lacking guanylyl cyclase-A (GC-A), a natriuretic peptide receptor, have pressure-independent cardiac hypertrophy. However, the mechanism underlying GC-A-mediated inhibition of hypertrophy remains to be elucidated. In present report, we examined role regulator G-protein signaling subtype 4 (RGS4), GTPase activating protein for G(q) and G(i), in antihypertrophic effects GC-A.In cultured myocytes, treatment atrial stimulated binding guanosine 3',5'-cyclic monophosphate-dependent kinase...
Most patients suffering from cancer die of metastatic disease. Surgical removal solid tumors is performed as an initial attempt to cure patients; however, surgery often accompanied with trauma, which can promote early recurrence by provoking detachment tumor cells into the blood stream or inducing systemic inflammation both. We have previously reported that administration atrial natriuretic peptide (ANP) during perioperative period reduces inflammatory response and has a prophylactic effect...
A small GTPase, Rho, participates in agonist‐induced cytoskeletal organization and gene expression many cell types including cardiac myocytes. However, little is known about the functions of Rho's downstream targets We examined role ROCK, a target ET‐1‐induced hypertrophic response. Y27632, selective ROCK inhibitor, inhibited increases natriuretic peptide production, size, protein synthesis, myofibrillar organization. In addition, dominant‐negative mutant p160 suppressed transcription BNP...
Induction of the atrial natriuretic peptide (ANP) gene is a common feature ventricular hypertrophy. A number cis-acting enhancer elements for several transcriptional activators have been shown to play central roles in regulation ANP expression, but much less known about contributions made by repressors. The neuron-restrictive silencer element (NRSE), also as repressor 1, mediates repression neuronal expression nonneuronal cells. We found that NRSE, which located 3′ untranslated region gene,...
Acute myocardial infarction (AMI) remains the leading cause of death in developed countries. Although reperfusion coronary arteries reduces mortality, it is associated with tissue injury. Endothelial P-selectin–mediated infiltration neutrophils plays a key role However, mechanism P-selectin induction not known. Here we show that infarct size after ischemia/reperfusion was significantly smaller mice lacking guanylyl cyclase-A (GC-A), natriuretic peptide receptor. The decrease accompanied by...
Abstract Recently, we have demonstrated that C-type natriuretic peptide (CNP) is produced in vascular endothelial cells (ECs). In the present study, investigated interaction of ECs and smooth muscle (SMCs) for production CNP its action on growth, using EC/SMC coculture system. The concentration CNP-like immunoreactivity medium was increased 60-fold within 48 hours with direct contact compared EC alone. Northern blot analysis revealed augmented expression mRNA coculture. accumulation...
Recent clinical trials have shown that systemic infusion of nesiritide, a recombinant human brain natriuretic peptide (BNP), improves hemodynamic parameters in acutely decompensated hearts. This suggests BNP exerts direct cardioprotective effect and might thus be useful therapeutic agent with which to treat acute myocardial infarction (MI). In the present study, we used BNP-transgenic (BNP-Tg) mice elevated plasma determine whether how contributes left ventricular remodeling healing after...
C-type natriuretic peptide (CNP) is known to play a role in the local regulation of vascular tone. We recently found that CNP also produced by cardiac ventricular cells. However, its effect on myocyte hypertrophy remains be elucidated. The present study investigated effects cultured and interaction between endothelin-1 (ET-1) signaling pathways. attenuated basal ET-1-augumented protein synthesis, atrial secretion, hypertrophy-related gene expression, GATA-4 MEF-2 DNA binding activities,...
Acute myocardial infarction (MI) initiates an increase in cardiac sympathetic nerve activity (CSNA), which ultimately exacerbates chronic dysfunction. Ghrelin (Ghr), a GH-releasing peptide, is effective treatment for improving function heart failure. Ghr also suppresses renal (SNA) and, therefore, may have important therapeutic benefits the early stages of acute MI: by reducing CSNA. In this study we hypothesized that administration prevent CSNA phase after MI. was continuously recorded...
Natriuretic peptides produced by the heart in response to cardiac overload exert cardioprotective and renoprotective effects eliciting natriuresis, reducing BP, inhibiting cell proliferation fibrosis. These also antagonize renin-angiotensin-aldosterone system, but whether this mechanism contributes their effect is unknown. Here, we examined kidneys of mice lacking guanylyl cyclase-A (GC-A) receptor for natriuretic under conditions high aldosterone dietary salt. After 4 weeks administering a...
Natriuretic peptides have been proposed as biomarkers of cardiovascular disease, especially heart failure. Brain natriuretic peptide (BNP) has also shown to be upregulated at the transcriptional and translational levels by pro-inflammatory cytokines in cardiac myocytes. Although we often measure plasma BNP cancer patients, it remains unknown whether cancer-related inflammation affects levels. We investigated relationship between human cancers.We retrospectively studied 2,923 patients whom...