Hitoshi Tachikawa

Niigata University, Niahi-niigata, Niigata, Japan

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Publications (34)99.35 Total impact

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    ABSTRACT: The aim was to evaluate the role of the combination of olmesartan, an angiotensin II (Ang II) receptor blocker (ARB), with daunorubicin (DNR) in reducing cardiac toxicity in rats. DNR was administered at a dose of 3 mg/kg/day every other day for 12 days. Olmesartan was administered orally every day for 12 days. Rats treated with DNR alone showed cardiac toxicity as evidenced by worsening cardiac function, elevation of malondialdehyde level in heart tissue and decreased in the level of total glutathione peroxidase activity; treatment with ARB reversed these changes. Furthermore, ARB treatment down-regulated matrix metalloproteinase-2 expression, myocardial expression of Ang II, attenuated the increased protein expressions of p67phox and Nox4 and reduced oxidative stress-induced DNA damage evaluated by expression of 8-hydroxydeoxyguanosine. In conclusion, the result demonstrated that Ang II and oxidative stress play a key role in anthracycline-induced cardiotoxicity and that treatment with ARB will be beneficial against DNR-induced cardiotoxicity.
    Free Radical Research 11/2010; 44(11):1369-77. DOI:10.3109/10715762.2010.509399 · 2.99 Impact Factor
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    ABSTRACT: Experimental autoimmune myocarditis (EAM) is mediated by myocardial infiltration by myosin-specific T-cells secreting inflammatory cytokines. In this study, rat models of EAM were prepared by injection with porcine cardiac myosin. One week after immunization, edaravone was administered intraperitoneally at 3 or 10 mg/kg/day to rats for 2 weeks. Cardiac function was measured by haemodynamic and echocardiographic studies and TUNEL assay was performed. Left ventricular (LV) expression of NADPH oxidase sub-units (p47(phox) and p67(phox)), pro-inflammatory cytokines (TNF-alpha), endoplasmic reticulum (ER) stress signalling proteins (GRP78, caspase-12 and GADD153) and mitogen-activated protein kinase (MAPK) family proteins (phospho-p38 MAPK and phospho-JNK) were measured by western blotting. Edaravone improved LV function in a dose-dependent manner. Central venous pressure was significantly low and LV ejection fraction and fractional shortening was significantly high in edaravone groups compared with those in the vehicle group. In addition, edaravone treatment down-regulated LV expressions of p47(phox), TNF-alpha, GADD153, phospho-p38 MAPK and phospho-JNK. Furthermore, the LV expressions of p67(phox), GRP78, caspase-12 and TUNEL-positive cells of rats with EAM treated with edaravone were significantly low compared with those of the vehicle group. These findings suggest that edaravone ameliorated the progression of EAM by inhibiting oxidative and ER stress and, subsequently, cardiac apoptosis.
    Free Radical Research 09/2010; 44(9):1082-90. DOI:10.3109/10715762.2010.499904 · 2.99 Impact Factor
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    ABSTRACT: Cardiovascular disease is a leading cause of death worldwide. Diabetes mellitus is a well-known and important risk factor for cardiovascular diseases. The occurrence of diabetic cardiomyopathy is independent of hypertension, coronary artery disease, or any other known cardiac diseases. There is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Diabetic cardiomyopathy is characterized by morphologic and structural changes in the myocardium and coronary vasculature mediated by the activation of various signaling pathways. Myocardial apoptosis, hypertrophy and fibrosis are the most frequently proposed mechanisms to explain cardiac changes in diabetic cardiomyopathy. Mammalian 14-3-3 proteins are dimeric phosphoserine-binding proteins that participate in signal transduction and regulate several aspects of cellular biochemistry. 14-3-3 protein regulates diabetic cardiomyopathy via multiple signaling pathways. This review focuses on emerging evidence suggesting that 14-3-3 protein plays a key role in the pathogenesis of the cardiovascular complications of diabetes, which underlie the development and progression of diabetic cardiomyopathy.
    Acta Physiologica Hungarica 10/2009; 96(3):277-87. DOI:10.1556/APhysiol.96.2009.3.3 · 0.75 Impact Factor
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    ABSTRACT: The important role of renin-angiotensin-aldosterone system blockade in the treatment of diabetes-induced cardiomyopathy and nephropathy has been clearly established. The present study examined the effect of angiotensin II type 1 receptor blocker (ARB) losartan on oxidative stress and cardio-renal function in streptozotocin (STZ)-induced diabetic rats. Losartan treatment resulted in improvement of myocardial function and suppressed cardiac and renal fibrosis compared with the diabetic group. Losartan treatment also down-regulated transforming growth factor-beta1 expression and attenuated the increased expression levels of p22(phox) and Nox4. Blood urea nitrogen (BUN) and urinary protein levels were increased significantly in the diabetic group. Losartan treatment significantly reduced proteinuria but not BUN level. Moreover, the elevated level of malondialdehyde in both heart and kidney were significantly reduced in the losartan-treated group compared with the diabetic group. These results provided evidence that oxidative stress plays a major role in diabetic rats induced by STZ, and treatment with the ARB might be beneficial for preventing the development and progression of diabetic disease.
    Biological & Pharmaceutical Bulletin 09/2009; 32(8):1411-6. · 1.78 Impact Factor
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    ABSTRACT: Torasemide is a long-acting loop diuretic that combines the effects of both furosemide and spironolactone. It has been reported that torasemide but not furosemide might attenuate myocardial remodeling accompanied by left ventricular (LV) dysfunction. However, nothing is known about the effect of torasemide, long-acting loop diuretic and spironolactone, an aldosterone receptor antagonist in a rat model of chronic heart failure (CHF). Therefore, we compared the therapeutic effects of torasemide, furosemide and spironolactone on the progression of LV remodeling in a rat model of CHF after experimental autoimmune myocarditis (EAM). EAM was elicited in Lewis rats by immunization with porcine cardiac myosin. Twenty-eight days after immunization, rats were treated for 28 days with torasemide, furosemide and spironolactone. Diuretic actions, heart weight/body weight, heart rate, mean blood pressure, myocardial function by echocardiography, cardiac fibrosis, myocyte diameter and cardiac aldosterone synthetase (CYP11B2) were evaluated. Increased cardiac CYP11B2, severe LV remodeling and resultant cardiac dysfunction was found in CHF rats, whereas decreased cardiac CYP11B2, less remodeling and improvement of cardiac function were found in torasemide- and spironolactone-treated CHF rats. Our results indicate that torasemide and spironolactone treatment significantly improved cardiac function and LV remodeling compared with furosemide treatment.
    Yakugaku zasshi journal of the Pharmaceutical Society of Japan 08/2009; 129(7):871-9. DOI:10.1248/yakushi.129.871 · 0.31 Impact Factor
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    ABSTRACT: Takotsubo cardiomyopathy is characterised by a reversible left ventricular wall motion abnormality that is observed as apical ballooning without significant coronary arterial stenosis; it occurs predominantly in postmenopausal women. Here, we report a case of Takotsubo cardiomyopathy after delivery in a patient with oestrogen deficiency due to Turner's syndrome. This case shows the pathogenic role of an inadequate oestrogen level in Takotsubo cardiomyopathy.
    International journal of cardiology 06/2009; 149(2):e78-9. DOI:10.1016/j.ijcard.2009.04.007 · 6.18 Impact Factor
  • Biological & Pharmaceutical Bulletin 01/2009; 32(8):1411-1416. DOI:10.1248/bpb.32.1411 · 1.78 Impact Factor
  • Journal of Molecular and Cellular Cardiology 10/2008; 45(4). DOI:10.1016/j.yjmcc.2008.09.630 · 5.22 Impact Factor
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    ABSTRACT: Hereby we report our observations derived from a pilot-study of 39 subjects (30 patients with coronary artery disease [CAD] and 9 non-CAD controls). In this work, we aimed to evaluate MPO-ANCA titer in the human coronary circulation for the first time; and examine its possible association with CAD and some cytokines/inflammatory markers. We found higher mean coronary MPO-ANCA titer in CAD subjects than in non-CAD controls; beside significant positive correlations between MPO-ANCA titers and both C-reactive protein and interleukin-6 levels. Thus, we might suggest the possible involvement of MPO-ANCA in coronary atherogenesis indirectly through modulating some pro-inflammatory cytokines/markers; that a large-scale study of MPO-ANCA in CAD patients may be warranted in the future.
    International journal of cardiology 09/2008; 128(1):114-6. DOI:10.1016/j.ijcard.2007.04.119 · 6.18 Impact Factor
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    ABSTRACT: Chymase has been known as a local angiotensin II-generating enzyme in the cardiovascular system in dogs, monkeys, hamsters, and humans; however, recently it was reported that chymase also has various other functions. Therefore, we decided to examine whether the inhibition of chymase improves disease conditions associated with the pathophysiology of dilated cardiomyopathy in rats and its possible mechanism of action as rat chymase is unable to produce angiotensin II. We examined the effect of TY-51469, a novel chymase inhibitor (0.1 mg/kg/day [group CYI-0.1, n = 15] and 1 mg/kg/day [group CYI-1, n = 15]), in myosin-immunized postmyocarditis rats. Another group of myosin-immunized rats was treated with vehicle (group V, n = 15). Age-matched normal rats without immunization (group N, n = 10) were also included in the study. After 4 weeks of treatment, we evaluated cardiac function; area of fibrosis; fibrogenesis; levels of transforming growth factor (TGF)-beta1 and collagen III; hypertrophy and its marker, atrial natriuretic peptide (ANP); and mast cell activity. Survival rate and myocardial functions improved dose-dependently with chymase inhibitor treatment after myosin immunization. A reduction in the percent area of myocardial fibrosis, fibrogenesis, myocardial hypertrophy, and mast cell activity along with a reduction in TGF-beta1, collagen III, and ANP levels in the myocardium were noted in postmyocarditis rats that received chymase inhibitor treatment. The treatment also decreased myocardial aldosterone synthase levels in those animals. Inhibition of chymase reduces the pathogenesis of postmyocarditis dilated cardiomyopathy and progression to heart failure by preventing the pathological remodeling and residual inflammation in rats.
    Experimental Biology and Medicine 11/2007; 232(9):1213-21. DOI:10.3181/0703-RM-85 · 2.23 Impact Factor
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    ABSTRACT: We have established a mouse model which shows the symptoms of coronary arteritis after consecutive injections of CAWS, which is released from Candida albicans. In this study, we examined neutrophil activation in the initial period after CAWS injection intraperitoneally. During 10 min to 16 h after the injection, blood profiles and neutrophil functions were determined. At the same time, levels of inflammatory cytokines and chemokines in plasma were measured. Furthermore, level of ICAM-1 as a marker of lesion in arterial endothelial cells was measured. Counts of the peripheral leukocytes increased immediately after CAWS injection, especially involving neutrophil. In vitro sensitivity of neutrophils to stimuli was enhanced. Moreover, proinflammatory cytokines (IL-1beta, IL-12 and IL-6) increased in plasma initially followed by an increase in IL-10, G-CSF, MIP-2 and soluble ICAM-1. Locally, ICAM-1 message in arterial walls was significantly increased 16 h after CAWS injection. A decrease in C3 levels was observed in plasma, suggesting complement activation and consumption. In summary, neutrophil activation occurred after CAWS injection, followed by complement activation, and production of proinflammatory cytokines chemokines and G-CSF which may be involved in development of coronary arteritis.
    Experimental and Molecular Pathology 05/2007; 82(2):220-6. DOI:10.1016/j.yexmp.2006.05.006 · 2.88 Impact Factor
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    ABSTRACT: Daunorubicin is an anthracycline anti-tumor agent; anthracycline chemotherapy in cancer can cause severe cardiomyopathy leading to a frequently fatal congestive heart failure; the first-line treatment is diuretics and digoxin. Recently, angiotensin-converting enzyme inhibitors have been shown to be effective in the treatment of such toxicity. The purpose of this study was to investigate the effects of angiotensin II type-1 receptor antagonist (candesartan) in a rat model of daunorubicin-induced cardiomyopathy. Rats were treated with a cumulative dose of 9 mg/kg body weight daunorubicin (i.v.). 28 days later, after the development of cardiomyopathy, animals were randomly assigned to candesartan-treated (5 mg/kg/day, p.o.) or vehicle-treated groups; age-matched normal rats were used as the control group. Candesartan treatment was continued for 28 days. Hemodynamic and echocardiographic parameters were measured, cardiac protein and mRNA were analyzed, and histopathological analyses of myocardial fibrosis, cell size and apoptosis were conducted. Following cardiomyopathy, left ventricular end diastolic pressure and left ventricular systolic dimension were significantly elevated; while % fractional shortening and Doppler E/A ratio were significantly reduced. Cardiomyopathic hearts showed significant increases in % fibrosis, % apoptosis, and myocyte diameter/body weight ratio; candesartan treatment reversed these changes. Fas-L protein overexpression in myopathic hearts was significantly suppressed by treatment with candesartan. Moreover, SERCA2 mRNA and protein expression were both down-regulated in myopathic hearts and restored to normal by candesartan treatment, significantly. Our findings suggest that candesartan treatment significantly improved the left ventricular function and reversed the myocardial pathological changes investigated in this model of daunorubicin-induced cardiomyopathy; suggesting its potentials in limiting daunorubicin cardiotoxicity.
    International Journal of Cardiology 07/2006; 110(3):378-85. DOI:10.1016/j.ijcard.2005.08.061 · 6.18 Impact Factor
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    ABSTRACT: Edaravone, a potent antioxidant, is currently being used in the management of acute ischemic stroke in relatively high-aged populations. Mitogen activated protein kinase (MAPK) pathways have been shown to play important roles in neuronal cell death. We examined the role of MAPK pathways and the effect of treatment with edaravone in the brain after cerebral ischemia-reperfusion (I/R) injury in a bilateral carotid artery occlusion (BCAO) model with ischemia for 85 min followed by reperfusion for 45 min in aged rats. Western immunoblotting, immunostaining, enzyme-linked immunosorbent assay (ELISA), spectrophotometry, terminal deoxynucleotidyl transferase nick end labeling (TUNEL) and triphenyl tetrazolium chloride (TTC) staining were performed to evaluate various proteins in the homogenate, c-Jun NH2-terminal kinase (JNK) in the tissue sections, protein carbonyl, glutathione peroxidase (GSHPx), apoptosis and infarct size, respectively. Our results showed that I/R injury resulted in a reduction of GSHPx, but protein carbonyl content and inducible nitric oxide synthase were increased. The activation of JNK and its downstream molecule c-Jun was significantly increased after injury, whereas the activities of p38 MAPK and extracellular-regulated kinase 1/2 were slightly but not significantly increased. Edaravone (3 mg/kg, i.v.) treatment significantly reduced all of these changes. Our findings suggest that the JNK pathway differentially mediates neuronal injury in aged rats after BCAO, and edaravone treatment significantly reduces the neuronal damage after I/R injury by inhibiting oxidative stress and the JNK-c-Jun pathway with concomitant inhibition of overall MAPK activity in the brains of aged rats.
    Biological & Pharmaceutical Bulletin 05/2006; 29(4):713-8. DOI:10.1248/bpb.29.713 · 1.78 Impact Factor
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    ABSTRACT: The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse is a model of human crescentic glomerulonephritis and vasculitis associated with the production of the myeloperoxidase (MPO)-specific antineutrophil cytoplasmic autoantibody (MPO-ANCA). Although the disease is mediated initially by mutation of the Fas gene (lpr), SCG/Kj mice also have non-Fas predisposing genetic factors. To define these factors, genome-wide quantitative trait locus (QTL) mapping was performed on female (B(6)x SCG/Kj) F(2) intercross mice. Fourteen non-Fas QTLs were identified. QTLs of glomerulonephritis were located on chromosomes 1, 10, 13, 16, and 17, vasculitis on chromosomes 1 and 17, splenomegaly on chromosome 1, hypergammaglobulinemia on chromosomes 1, 2, 4, 6, 7, 11, 13, and 17, antinuclear Ab on chromosomes 1, 8, 10, and 12, and MPO-ANCA production on chromosomes 1 and 10. Significant QTLs derived from SCG/Kj on chromosomes 1, 2, 7, and 13 were designated Scg-1 to Scg-5, respectively, and those derived from B(6) on chromosomes 4, 6, 17, and 10 were designated Sxb-1 to Sxb-4, respectively. Two loci linked to MPO-ANCA production on chromosomes 1 and 10 were designated Man-1 and Man-2 (for MPO-ANCA), respectively. Although both Scg-1 and Scg-2 were on chromosome 1 and shared several functions, it was of interest that aberrant MPO-ANCA production was exclusively controlled by Man-1, the centromeric half region of the Scg-2 chromosomal segment. We also examined the epistatic effects between the lpr mutation and non-Fas susceptibility genes. QTLs are discussed in relation to previously described loci, with emphasis on their candidate genes.
    The Journal of Immunology 04/2006; 176(6):3662-73. DOI:10.4049/jimmunol.176.6.3662 · 5.36 Impact Factor
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    ABSTRACT: Clinical implication of mechanical alternans is yet unclear. It may suggest the risk for sudden death in patients with chronic heart failure. Two cases with dilated cardiomyopathy showed mechanical alternans during diagnostic cardiac catheterization. They suddenly died due to ventricular fibrillation before the induction of beta-blocker therapy. Patients with mechanical alternans should be treated under intense monitoring until the induction of beta-blocker therapy.
    Pacing and Clinical Electrophysiology 01/2006; 28(12):1347-9. DOI:10.1111/j.1540-8159.2005.00276.x · 1.25 Impact Factor
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    ABSTRACT: Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality. Occurrence of myocardial fibrosis is an important event in the ventricular remodeling process, which takes place during DCM. Mast cells are well known inflammatory cells implicated in various biological phenomena. The involvement of mast cells in the development of myocardial fibrosis of DCM in rats after autoimmune myocarditis remains unknown. Nine-week-old male Lewis rats were immunized with cardiac myosin and divided into vehicle treated (group V) and disodium cromoglycate (DSCG), a mast cell stabilizer (24 mg/kg i.p.) treated (group DSCG) groups. The animals were sacrificed after 60 d of immunization. The myocardium was excised and preserved for histopathology and protein analysis. Myocardial levels of transforming growth factor (TGF) beta1 and collagen-III were quantified. Staining of mast cells was performed by toluidine blue. A significant correlation was obtained between myocardial fibrosis and cardiac mast cell density. DSCG reduced myocardial fibrosis besides preventing infiltration and degranulation of mast cells. Our findings confirm the active participation of mast cells in the progression of myocardial fibrosis in rats with postmyocarditis DCM.
    Biological & Pharmaceutical Bulletin 12/2005; 28(11):2128-32. DOI:10.1248/bpb.28.2128 · 1.78 Impact Factor
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    ABSTRACT: Aldosterone blockade reduces morbidity and mortality in patients with heart failure. We studied the effects of eplerenone, a novel aldosterone blocker, on the progression of left ventricular dysfunction and remodeling in rats with dilated cardiomyopathy after autoimmune myocarditis. Twenty-eight days after immunization, the surviving Lewis rats were randomized to 1 month's oral treatment with low-dose eplerenone (group L), high-dose eplerenone (group H) or vehicle (group V). Five of 15 (33%) rats in group V and 3 of 15 (20%) rats in group L died during the course of treatment. High-dose eplerenone significantly reduced cardiomyocyte hypertrophy, heart weight and heart weight to body weight ratio. Eplerenone improved left ventricular function in a dose-dependent manner. Central venous pressure and left ventricular end-diastolic pressure were lower, and +/-dP/dt and fractional shortening were higher in group H than group V. Eplerenone also attenuated myocardial fibrosis and reduced left ventricular mRNA expressions of TGF-beta(1) and collagen-III. Our results indicate that treatment with eplerenone improved left ventricular dysfunction and attenuated left ventricular remodeling in rats with heart failure.
    Pharmacology 03/2005; 73(2):81-8. DOI:10.1159/000081267 · 1.58 Impact Factor
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    ABSTRACT: It is unclear how amiodarone therapy exerts its effects on left ventricular remodeling and cardiac sympathetic nerve function in chronic heart failure. We investigated long-term effects of amiodarone on rat dilated cardiomyopathy after healing of cardiac myosin-induced autoimmune myocarditis. Rats were treated with oral amiodarone or vehicle for 6 weeks. We determined cardiac function, left ventricular remodeling, and cardiac sympathetic nerve function with iodine-125-labeled metaiodobenzylguanidine ([I125]MIBG). Amiodarone treatment improved left ventricular pressure, central venous pressure, and rate of isovolumetric contraction and decreased ventricular weight (P<0.005). Expression of cytokine mRNA was unchanged; expression of atrial natriuretic peptide, collagen III, and transforming growth factor-beta1 mRNA was decreased in amiodarone-treated rats (P<0.05). Phenotype of myosin heavy chain was moved toward that of normal rats by amiodarone. Initial myocardial uptake of MIBG decreased by 67% (P<0.001) and washout rate accelerated by 221% in rats with chronic heart failure compared with normal rats. Whereas amiodarone decreased the initial uptake by 71% in normal rats, amiodarone decelerated the early washout and the late washout and improved the late myocardial distribution of MIBG in rats with chronic heart failure (257% compared with vehicle-treated rats with chronic heart failure; P<0.01). In proportion to MIBG distributions, cardiac tissue catecholamines were increased by amiodarone treatment. Long-term amiodarone treatment prevented left ventricular remodeling and improved cardiac function in rat dilated cardiomyopathy. Long-term amiodarone treatment also restored cardiac sympathetic tone to hold norepinephrine in the heart.
    Circulation 03/2005; 111(7):894-9. DOI:10.1161/01.CIR.0000155610.49706.D2 · 14.95 Impact Factor
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    ABSTRACT: We examined effects of an angiotensin-II receptor blockers, candesartan cilexetil, in rats with dilated cardiomyopathy after autoimmune myocarditis. Candesartan cilexetil showed angiotensin-II blocking action in a dose-dependent manner in rats with dilated cardiomyopathy. Twenty-eight days after immunization, surviving Lewis rats were divided into four groups and given candesartan cilexetil at 0.05 mg/kg, 0.5 mg/kg or 5 mg/kg per day (Group-C0.05, n = 15, Group-C0.5, n = 15 and Group-C5, n = 15, respectively) or vehicle alone (Group-V, n = 15). After oral administration for 1 month, the left ventricular end-diastolic pressure and heart weight/body weight ratio were lower in Group-C0.05 (13.3+/-1.1 mmHg and 3.7+/-0.2 g/kg, respectively), in Group-C0.5 (8.0+/-0.9 mmHg and 3.3+/-0.1 g/kg, respectively) and in Group-C5 (5.5+/-1 mmHg and 3.1+/-0.1 g/kg, respectively) than in Group-V (13.5+/-1.0 mmHg and 3.8+/-0.2 g/kg, respectively). The area of myocardial fibrosis was also lower in Group-C0.05 (25+/-3%), in Group-C0.5 (20+/-3%), and in Group-C5 (12+/-1%) than in Group-V (32+/-4%). Furthermore, expressions of transforming growth factor-beta1 and collagen-III mRNA were suppressed in Group-C0.05 (349+/-23% and 395+/-22%, respectively), Group-C0.5 (292+/-81% and 364+/-42%, respectively) and in Group-C5 (204+/-63% and 259+/-33%, respectively) compared with those in Group-V (367+/-26% and 437+/-18%, respectively). These results suggest that candesartan cilexetil can improve the function of inefficient heart.
    Molecular and Cellular Biochemistry 02/2005; 269(1-2):137-42. DOI:10.1007/s11010-005-3446-9 · 2.39 Impact Factor
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    ABSTRACT: Progression of acute myocarditis involves a variety of inflammatory events. Mast cells have been implicated as the source of various cytokines, chemokines and histamine in acute inflammation and fibrosis. Interleukin (IL)-10 has well-known immunomodulatory actions that are exerted during the recovery phase of myocarditis. In this study, 9-week-old male Lewis rats were immunized with cardiac myosin. A plasmid vector expressing mouse IL-10 cDNA (800 mug per rat) was then transferred three times (7, 12 and 17 days after immunization) into the tibialis anterior muscles of the rats by electroporation. Microscopic examination of mast cells was carried out on toluidine blue-stained transverse sections of the mid ventricles. Mouse IL-10 gene transfer significantly reduced mast cell density, cardiac histamine concentration and mast cell growth, and prevented mast cell degranulation. Furthermore, improvement in both myocardial function and the overall condition of the rats was evident from the reduction in the heart weight-to-body weight ratio and inflammatory infiltration as well as improvement in hemodynamic and echocardiographic parameters. These findings suggest that IL-10 gene transfer by electroporation protected against myocarditis via mast cell inhibition.
    European Journal of Immunology 01/2005; 34(12):3508-15. DOI:10.1002/eji.200425147 · 4.52 Impact Factor

Publication Stats

369 Citations
99.35 Total Impact Points


  • 2008–2010
    • Niigata University
      • • Department of Internal Medicine
      • • Graduate School of Medical and Dental Sciences
      Niahi-niigata, Niigata, Japan
  • 2003–2009
    • Niigata University of Pharmacy and Applied Life Sciences
      Niahi-niigata, Niigata, Japan
  • 2007
    • Stanford University
      • Department of Chemical and Systems Biology
      Palo Alto, California, United States
  • 2006–2007
    • National Institute of Infectious Diseases, Tokyo
      Edo, Tōkyō, Japan