20 results on '"Matsui-Hirai, H."'
Search Results
2. NADPH oxidase inhibitor, apocynin, restores the impaired endothelial‐dependent and ‐independent responses and scavenges superoxide anion in rats with type 2 diabetes complicated by NO dysfunction
- Author
-
Hayashi, T., primary, Juliet, P. A. R., additional, Kano‐Hayashi, H., additional, Tsunekawa, T., additional, Dingqunfang, D., additional, Sumi, D., additional, Matsui‐Hirai, H., additional, Fukatsu, A., additional, and Iguchi, A., additional
- Published
- 2004
- Full Text
- View/download PDF
3. Cerivastatin, a hydroxymethylglutaryl coenzyme a reductase inhibitor, improves endothelial function in elderly diabetic patients within 3 days.
- Author
-
Tsunekawa, T, Hayashi, T, Kano, H, Sumi, D, Matsui-Hirai, H, Thakur, N K, Egashira, K, and Iguchi, A
- Published
- 2001
4. Biological characterization of adipose-derived regenerative cells used for the treatment of stress urinary incontinence.
- Author
-
Okabe YT, Shimizu S, Suetake Y, Matsui-Hirai H, Hasegawa S, Takanari K, Toriyama K, Kamei Y, Yamamoto T, Mizuno M, and Gotoh M
- Subjects
- Adipose Tissue, Cells, Cultured, Female, Humans, Male, Placenta Growth Factor, Urethra surgery, Vascular Endothelial Growth Factor A, Urinary Incontinence, Stress therapy
- Abstract
Objective: To assess the characteristics of adipose-derived regenerative cells, and provide supportive data explaining the mechanism of efficacy observed for the use of these cells in the treatment of stress urinary incontinence., Methods: Adipose tissues were harvested by abdominal liposuction from healthy donors and patients with stress urinary incontinence. Adipose-derived regenerative cells were isolated from tissues using the Celution system, and assessed for their characteristics and ability to differentiate into smooth muscle cells., Results: Adipose-derived regenerative cells isolated by the Celution system developed into fibroblastic colonies. Flow cytometric analysis of adipose-derived stem cell markers showed that adipose-derived regenerative cells were positive for CD34 and CD44, and negative for CD31. Immunofluorescence staining after differentiation showed that colony-forming cells were positive for alpha-smooth muscle actin, calponin and desmin, which are smooth muscle cell markers. A cytokine release assay showed that adherent cells secreted cytokines associated with angiogenesis, including vascular endothelial growth factor-A, angiopoietin-2 and placental growth factor., Conclusions: Adipose-derived regenerative cells collected by the Celution system might have clonogenic capacity and an angiogenetic function. These properties might contribute to the mechanisms through which regenerative cell therapy by periurethral injection of autologous adipose-derived regenerative cells ameliorates stress urinary incontinence., (© 2020 The Japanese Urological Association.)
- Published
- 2021
- Full Text
- View/download PDF
5. Dose-dependent modulatory effects of insulin on glucose-induced endothelial senescence in vitro and in vivo: a relationship between telomeres and nitric oxide.
- Author
-
Matsui-Hirai H, Hayashi T, Yamamoto S, Ina K, Maeda M, Kotani H, Iguchi A, Ignarro LJ, and Hattori Y
- Subjects
- Aging metabolism, Animals, Aorta, Atherosclerosis physiopathology, Cells, Cultured, Cellular Senescence drug effects, Dose-Response Relationship, Drug, Endothelial Cells cytology, Endothelial Cells metabolism, Endothelium, Vascular cytology, Endothelium, Vascular metabolism, Glucose, Humans, Hypoglycemic Agents metabolism, Insulin physiology, Nitric Oxide Synthase Type III genetics, Nitric Oxide Synthase Type III metabolism, RNA, Small Interfering genetics, Rats, Telomerase metabolism, Umbilical Veins drug effects, Umbilical Veins metabolism, beta-Galactosidase metabolism, Diabetes Mellitus, Experimental drug therapy, Endothelial Cells drug effects, Endothelium, Vascular drug effects, Hypoglycemic Agents pharmacology, Insulin pharmacology, Nitric Oxide metabolism, Telomere physiology
- Abstract
The elderly are prone to postprandial hyperglycemia that increases their cardiovascular risk. Although insulin therapy is necessary to treat diabetes, high plasma concentrations of insulin may cause the development of atherosclerosis and accelerate endothelial senescence. We assumed that high glucose causes stress-induced premature senescence and replicative senescence and examined the regulatory role of insulin in endothelial senescence and functions under different glucose conditions. Exposure of human endothelial cells to high glucose (22 mM) for 3 days increased senescence-associated-β-galactosidase activity, a senescence marker, and decreased telomerase activity, a replicative senescence marker. Physiological concentrations of insulin preserved telomere length and delayed endothelial senescence under high-glucose conditions. The effect of insulin under high-glucose conditions was associated with reduced reactive oxygen species and increased nitric oxide (NO). Small interfering RNA targeting endothelial NO synthase reduced the antisenescence effects of insulin. Physiological concentrations of insulin also reversed high glucose-induced increases in p53 and vascular cell adhesion molecule-1 and decreases in senescence marker protein-30. On the other hand, when insulin was given at any concentrations under normal glucose or at high concentrations under high glucose, its ability to promote cellular senescence was unrelated to endothelial NO. Finally, streptozotocin-induced diabetes showed more senescent cells in the aortic endothelium of aged rats compared with age-matched control and insulin-treated animals. Conclusively, the regulatory effects of insulin on endothelial senescence were modulated by the glucose environment. These data may help explain insulin's complicated roles in atherosclerosis in the elderly.
- Published
- 2011
- Full Text
- View/download PDF
6. Clinical factors such as B-type natriuretic peptide link to factor VII, endothelial NO synthase and estrogen receptor alpha polymorphism in elderly women.
- Author
-
Funami J, Hayashi T, Nomura H, Ding QF, Ishitsuka-Watanabe A, Matsui-Hirai H, Ina K, Zhang J, Yu ZY, and Iguchi A
- Subjects
- Aged, Aged, 80 and over, Atherosclerosis blood, DNA genetics, Estrogen Receptor alpha genetics, Factor VII genetics, Female, Genotype, Humans, Japan, Middle Aged, Nitric Oxide Synthase Type III genetics, Thrombosis blood, Aging genetics, Atherosclerosis genetics, Natriuretic Peptide, Brain blood, Polymorphism, Single Nucleotide, Thrombosis genetics
- Abstract
Aims: This study evaluated the presence of genetic mutations in relation to thrombosis or atherosclerosis in elderly women., Main Methods: This is an observational study of 93 Japanese women with a mean age of 80.9 years recruited from outpatient clinics of Nagoya University and its related hospitals. Ten single nucleotide polymorphisms (SNPs) were studied. Each gene studied acts in or is related to either blood coagulation (factor V Leiden, prothrombin G20210A, factor XIII Val34Leu, factor VII Arg353Gln, MTHFR C677T, beta-fibrinogen G-455A, PAI-1 4G/5G), metabolic syndrome-related pathways (PPARalpha Leu162Val), or endothelium/estrogen system (eNOS Glu298Asp, ERalpha IVS1-401). SNPs were analyzed for their relation to clinical values including lipids, B-type natriuretic peptide (BNP), fasting plasma glucose, tumor necrosis factor-alpha, interleukin-6, cyclic GMP, and nitric oxide metabolites., Key Findings: Comparisons between the distributions of different genotypes and clinical values showed three relationships. First, factor VII Arg353Gln and HDL-cholesterol (HDL-C) were linked to Arg/Arg carriers at higher levels (P=.049). The HDL-C to LDL-cholesterol ratio supported this link (P=.027). Second, eNOS Glu298Asp and triglycerides were linked to Glu/Glu carriers at higher levels (P=.031). Third, ERalpha IVS1-401 and BNP were related to CC genotype at lower levels (P=.031). Additionally, the last two relations showed that genotype does not influence the demarcation line of biomarkers, but the plasma/serum levels of biomarkers instead., Significance: Correlations of factor VII Arg353Gln with HDL-C and eNOS Glu298Asp with triglycerides are new findings. Polymorphisms in the endothelium/estrogen system and the heart failure marker BNP are also correlated, with ERalpha IVS1-401 being the first identified marker. SNPs may be helpful for understanding the pathophysiology of atherosclerotic diseases in elderly women.
- Published
- 2009
- Full Text
- View/download PDF
7. Nitric oxide and endothelial cellular senescence.
- Author
-
Hayashi T, Yano K, Matsui-Hirai H, Yokoo H, Hattori Y, and Iguchi A
- Subjects
- Animals, Endothelium, Vascular metabolism, Estrogens physiology, Glucose metabolism, Humans, Telomere physiology, Cellular Senescence physiology, Endothelium, Vascular physiology, Nitric Oxide physiology
- Abstract
Cellular senescence is characterized by permanent exit from the cell cycle and the appearance of distinct morphological and functional changes associated with an impairment of cellular homeostasis. Many studies support the occurrence of vascular endothelial cell senescence in vivo, and the senescent phenotype of endothelial cells can be transformed from anti-atherosclerotic to pro-atherosclerotic. Thus, endothelial cell senescence promotes endothelial dysfunction and may contribute to the pathogenesis of age-associated vascular disorders. Emerging evidence suggests that increasing nitric oxide (NO) bioavailability or endothelial NO synthase (eNOS) activity activates telomerase and delays endothelial cell senescence. In this review, we discuss the potential mechanisms underlying the ability of NO to prevent endothelial cell senescence and describe the possible changes in the NO-mediated anti-senescence effect under pathophysiological conditions, including oxidative stress and hyperglycemia. Further understanding of the mechanisms underlying the anti-senescence effect of NO in endothelial cells will provide insights into the potential of eNOS-based anti-senescence therapy for age-associated vascular disorders.
- Published
- 2008
- Full Text
- View/download PDF
8. Possible usefulness of apocynin, an NADPH oxidase inhibitor, for nitrate tolerance: prevention of NO donor-induced endothelial cell abnormalities.
- Author
-
Fukatsu A, Hayashi T, Miyazaki-Akita A, Matsui-Hirai H, Furutate Y, Ishitsuka A, Hattori Y, and Iguchi A
- Subjects
- Animals, Cattle, Cells, Cultured, Dose-Response Relationship, Drug, Drug Combinations, Drug Tolerance physiology, Enzyme Inhibitors administration & dosage, Acetophenones administration & dosage, Endothelial Cells drug effects, Endothelial Cells metabolism, NADPH Oxidases antagonists & inhibitors, Nitrates metabolism, Nitric Oxide Donors administration & dosage, Reactive Oxygen Species metabolism
- Abstract
The long-term benefits of nitroglycerin therapy are limited by tolerance development. Understanding the precise nature of mechanisms underlying nitroglycerin-induced endothelial cell dysfunction may provide new strategies to prevent tolerance development. In this line, we tested interventions to prevent endothelial dysfunction in the setting of nitrate tolerance. When bovine aortic endothelial cells (BAECs) were continuously treated with nitric oxide (NO) donors, including nitroglycerin, over 2-3 days, basal production of nitrite and nitrate (NO(x)) was diminished. The diminished basal NO(x) levels were mitigated by intermittent treatment allowing an 8-h daily nitrate-free interval during the 2- to 3-day treatment period. Addition of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin restored the basal levels of NO(x) that were decreased by continuous nitroglycerin treatment of BAECs. Apocynin caused significant improvement of increased mRNA and protein levels of endothelial nitric oxide synthase (eNOS) in BAECs given nitroglycerin continuously over the treatment period. Apocynin also reduced endothelial production of reactive oxygen species (ROS) after continuous nitroglycerin treatment. These results showed an essential similarity to the effects of a nitrate-free interval. Application of the NOS inhibitor N(omega)-nitro- l-arginine methyl ester caused a recovery effect on basal NO(x) and eNOS expression but was without effect on ROS levels in continuously NO donor-treated BAECs. In conclusion, the present study characterized abnormal features and functions of endothelial cells following continuous NO donor application. We suggest that inhibition of NADPH oxidase, by preventing NO donor-induced endothelial dysfunction, may represent a potential therapeutic strategy that confers protection from nitrate tolerance development.
- Published
- 2007
- Full Text
- View/download PDF
9. beta1 antagonist and beta2 agonist, celiprolol, restores the impaired endothelial dependent and independent responses and decreased TNFalpha in rat with type II diabetes.
- Author
-
Hayashi T, Juliet PA, Miyazaki-Akita A, Funami J, Matsui-Hirai H, Fukatsu A, and Iguchi A
- Subjects
- Animals, Aorta, Abdominal metabolism, Atherosclerosis metabolism, Atherosclerosis prevention & control, Blood Pressure drug effects, Body Weight drug effects, Celiprolol pharmacology, Diabetes Mellitus, Experimental metabolism, Diabetes Mellitus, Type 2 metabolism, Diabetic Angiopathies metabolism, Diabetic Angiopathies prevention & control, Male, Nitrates blood, Nitric Oxide metabolism, Nitrites blood, Rats, Rats, Long-Evans, Superoxides metabolism, Adrenergic beta-1 Receptor Antagonists, Adrenergic beta-2 Receptor Agonists, Celiprolol therapeutic use, Diabetes Mellitus, Experimental complications, Diabetes Mellitus, Type 2 complications, Endothelium, Vascular metabolism, Tumor Necrosis Factor-alpha metabolism
- Abstract
Unlabelled: The effect of beta antagonists in the diabetic vascular lesion is controversial. We investigated the effect of celiprolol hydrochloride, a beta1 antagonist and mild beta2 agonist, on the lesions and function in type II male Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats. OLETF rats were fed regular chow with or without atenolol (25 mg/kg/day) or celiprolol (100 mg/kg/day) treatment (group DM, no treatment; group DM-a, atenolol treatment; group DM-c, celiprolol treatment), and treatment was continued for 31 days. Separately, normoglycemic control rats, LETO, were prepared as group C. On day 3, endothelial cells of the right internal carotid artery were removed by balloon injury, and the rats were evaluated 4 weeks after balloon injury. The plasma glucose and lipid levels were unchanged throughout the treatment period. Intimal thickening was observed in the right carotid artery in the DM and DM-a groups; however, little thickening was observed in those of DM-c rats. Acetylcholine-induced NO-dependent relaxation in arteries was improved in DM-c rats compared with DM and DM-a rats (maximum relaxation DM 30.8+/-4.5, DM-a 37.4+/-3.9, DM-c 48.8+/-4.6%, *P<0.05 vs. DM for DM-c rats). Tone-related basal NO release and acetylcholine-induced NO-dependent relaxation in the arteries and plasma NO(x) (sum of NO(2)(-) and NO(3)(-)) were greater in DM-c and C groups than in DM and DM-a groups. The serum TNFalpha levels did not increase in DM-c rats compared with those of the DM or DM-a groups, and were comparable with those of group C., Conclusion: In conclusion, Celiprolol improves endothelial function in the arteries of OLETF rats, and further restore it 4 weeks after endothelial denudation in the arteries of OLETF rats. NO and O(2)(-) may have a role in the important underlying mechanisms by reducing the TNFalpha levels.
- Published
- 2007
- Full Text
- View/download PDF
10. Endothelial cellular senescence is inhibited by nitric oxide: implications in atherosclerosis associated with menopause and diabetes.
- Author
-
Hayashi T, Matsui-Hirai H, Miyazaki-Akita A, Fukatsu A, Funami J, Ding QF, Kamalanathan S, Hattori Y, Ignarro LJ, and Iguchi A
- Subjects
- Atherosclerosis etiology, Atherosclerosis metabolism, Atherosclerosis pathology, Atherosclerosis prevention & control, Cells, Cultured, Diabetic Angiopathies etiology, Diabetic Angiopathies metabolism, Diabetic Angiopathies pathology, Diabetic Angiopathies prevention & control, Endothelial Cells metabolism, Female, Humans, Menopause, Nitric Oxide metabolism, Nitric Oxide Synthase Type III genetics, Reactive Oxygen Species metabolism, Telomerase metabolism, Transfection, Cellular Senescence drug effects, Endothelial Cells cytology, Endothelial Cells drug effects, Nitric Oxide pharmacology
- Abstract
Senescence may contribute to the pathogenesis of atherosclerosis. Although the bioavailability of nitric oxide (NO) is limited in senescence, the effect of NO on senescence and its relationship to cardiovascular risk factors have not been investigated fully. We studied these factors by investigating senescence-associated beta-galactosidase (SA-beta-gal) and human telomerase activity in human umbilical venous endothelial cells (HUVECs). Treatment with NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-aminoethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO) and transfection with endothelial NO synthase (eNOS) into HUVECs each decreased the number of SA-beta-gal positive cells and increased telomerase activity. The NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) abolished the effect of eNOS transfection. The physiological concentration of 17beta-estradiol activated hTERT, decreased SA-beta-gal-positive cells, and caused cell proliferation. However, ICI 182780, an estrogen receptor-specific antagonist, and L-NAME each inhibited these effects. Finally, we investigated the effect of NO bioavailability on high glucose-promoted cellular senescence of HUVECs. Inhibition by eNOS transfection of this cellular senescence under high glucose conditions was less pronounced. Treatment with L-arginine or L-citrulline of eNOS-transfected cells partially inhibited, and combination of L-arginine and L-citrulline with antioxidants strongly prevented, high glucose-induced cellular senescence. These data demonstrate that NO can prevent endothelial senescence, thereby contributing to the anti-senile action of estrogen. The ingestion of NO-boosting substances, including L-arginine, L-citrulline, and antioxidants, can delay endothelial senescence under high glucose. We suggest that the delay in endothelial senescence through NO and/or eNOS activation may have clinical utility in the treatment of atherosclerosis in the elderly.
- Published
- 2006
- Full Text
- View/download PDF
11. Selective iNOS inhibitor, ONO1714 successfully retards the development of high-cholesterol diet induced atherosclerosis by novel mechanism.
- Author
-
Hayashi T, Matsui-Hirai H, Fukatsu A, Sumi D, Kano-Hayashi H, Rani P JA, and Iguchi A
- Subjects
- Animals, Aorta, Thoracic enzymology, Aorta, Thoracic pathology, Arginine pharmacology, Atherosclerosis drug therapy, Atherosclerosis pathology, Blotting, Western, Cholesterol, Dietary blood, Cyclic GMP metabolism, Endothelium, Vascular enzymology, Endothelium, Vascular pathology, Heterocyclic Compounds, 2-Ring pharmacology, Immunohistochemistry, Macrophages pathology, Male, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide metabolism, Nitric Oxide Synthase Type II metabolism, Nitric Oxide Synthase Type III genetics, Nitric Oxide Synthase Type III metabolism, RNA, Messenger metabolism, Rabbits, Reactive Oxygen Species metabolism, Up-Regulation drug effects, Vasodilation drug effects, Amidines pharmacology, Atherosclerosis prevention & control, Cholesterol, Dietary pharmacology, Enzyme Inhibitors pharmacology, Nitric Oxide Synthase Type II antagonists & inhibitors
- Abstract
Objective: We have reported that inducible nitric oxide synthase (iNOS) is present only in deep areas of plaque in atherosclerosis. However, the role of iNOS in the development of atherosclerosis is not well known. We therefore investigated the relevance of iNOS inhibition., Methods and Results: Seven groups of male rabbits were fed a 0.5% high-cholesterol diet (HCD) for 8 weeks. Gp1-HCD was fed HCD only; Gp2-O17 was fed HCD with ONO1714, an iNOS inhibitor; Gp3-AG was fed HCD with amino-guanidine (AG), an iNOS inhibitor; Gp4-AR was fed HCD with l-arginine; Gp5-AR-O17 was fed HCD with l-arginine with ONO1714; Gp6-LNA was fed HCD with l-NAME (a NOS inhibitor); and Gp7-LN-O17 was fed HCD with l-NAME plus ONO1714. ONO1714 decreased atherosclerosis by about 70% (area occupied by lesions: 3.0+/-0.4% in Gp2-O17 versus 10.3+/-1.6% in Gp1-HCD) and also decreased atherosclerosis in Gp7-LN-O17. The ONO compound enhanced the atheroprotective effect of l-arginine. Amino-guanidine also showed an anti-atherosclerotic effect. Tone-related basal NO release and acetylcholine-induced NO-dependent relaxation were improved in Gp2-O17 and Gp5-AR-O17. O(2)(-) release was decreased in Gp2-O17 and Gp7-LN-O17., Conclusion: ONO1714 retards the progression of atherosclerosis in rabbits. Although the up-regulation of endothelial nitric oxide synthase (eNOS) and the decrease of O(2)(-) may play roles in this retardation, the inhibition of iNOS may be the principal factor, alone was not sufficient.
- Published
- 2006
- Full Text
- View/download PDF
12. l-Citrulline and l-arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits.
- Author
-
Hayashi T, Juliet PA, Matsui-Hirai H, Miyazaki A, Fukatsu A, Funami J, Iguchi A, and Ignarro LJ
- Subjects
- Animals, Antioxidants administration & dosage, Aorta, Thoracic metabolism, Aorta, Thoracic pathology, Arteriosclerosis drug therapy, Arteriosclerosis pathology, Ascorbic Acid administration & dosage, Cyclic AMP Response Element-Binding Protein biosynthesis, Cyclic GMP metabolism, DNA-Binding Proteins biosynthesis, Endothelium, Vascular pathology, Humans, Male, Nitrates metabolism, Nitric Oxide Synthase biosynthesis, Nitric Oxide Synthase Type III, Nitrites metabolism, Oxidation-Reduction drug effects, Proto-Oncogene Proteins biosynthesis, Rabbits, Superoxides metabolism, Transcription Factors biosynthesis, Vasodilation drug effects, Vitamin E administration & dosage, ets-Domain Protein Elk-1, Arginine administration & dosage, Arteriosclerosis metabolism, Citrulline administration & dosage, Diet, Atherogenic, Endothelium, Vascular metabolism
- Abstract
The objective of this study was to evaluate the influence of ingested l-arginine, l-citrulline, and antioxidants (vitamins C and E) on the progression of atherosclerosis in rabbits fed a high-cholesterol diet. The fatty diet caused a marked impairment of endothelium-dependent vasorelaxation in isolated thoracic aorta and blood flow in rabbit ear artery in vivo, the development of atheromatous lesions and increased superoxide anion production in thoracic aorta, and increased oxidation-sensitive gene expression [Elk-1 and phosphorylated cAMP response element-binding protein]. Rabbits were treated orally for 12 weeks with l-arginine, l-citrulline, and/or antioxidants. l-arginine plus l-citrulline, either alone or in combination with antioxidants, caused a marked improvement in endothelium-dependent vasorelaxation and blood flow, dramatic regression in atheromatous lesions, and decrease in superoxide production and oxidation-sensitive gene expression. These therapeutic effects were associated with concomitant increases in aortic endothelial NO synthase expression and plasma NO(2)(-)+NO(3)(-) and cGMP levels. These observations indicate that ingestion of certain NO-boosting substances, including l-arginine, l-citrulline, and antioxidants, can abrogate the state of oxidative stress and reverse the progression of atherosclerosis. This approach may have clinical utility in the treatment of atherosclerosis in humans.
- Published
- 2005
- Full Text
- View/download PDF
13. A new HMG-CoA reductase inhibitor, pitavastatin remarkably retards the progression of high cholesterol induced atherosclerosis in rabbits.
- Author
-
Hayashi T, Rani P JA, Fukatsu A, Matsui-Hirai H, Osawa M, Miyazaki A, Tsunekawa T, Kano-Hayashi H, Iguchi A, Sumi D, and Ignarro LJ
- Subjects
- Administration, Oral, Animals, Arteriosclerosis veterinary, Biological Availability, Cholesterol, HDL blood, Disease Models, Animal, Disease Progression, Female, Nitric Oxide pharmacology, Rabbits, Triglycerides blood, Up-Regulation, Arteriosclerosis drug therapy, Arteriosclerosis physiopathology, Enzyme Inhibitors pharmacology, Quinolines pharmacology
- Abstract
Background: The remarkable anti-atherosclerotic effects of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor have not been demonstrated in diet induced severe hyperlipidemia in rabbit model., Objective: We have investigated the effect of pitavastatin, a newly developed statin, on atherosclerosis in rabbits., Methods and Results: Oophorectomized female NZW rabbits were fed 0.3% cholesterol chow for 12 weeks with or without pitavastatin (0.1mg/kg per day) (Gp.NK and HCD). The level of serum cholesterol was decreased in Gp.NK compared with Gp.HCD (772.8 +/- 70.2 versus 1056.9 +/- 108.3 mg/d), whereas no significant alterations were observed in triglyceride and HDL-cholesterol. NO dependent response stimulated by acetylcholine and calcium ionophore A23187 and tone related basal NO response induced by N(G)-monomethyl-l-arginine acetate were all improved by pitavastatin treatment. Pitavastatin treatment increased the level of cyclic GMP in the aorta of cholesterol fed rabbits. In the aorta, the expression of eNOS mRNA was significantly up regulated and O(2)(-) production was slightly reduced in Gp.NK animals. Atherosclerotic area was significantly decreased in aortic arch and thoracic aorta from Gp.NK compared with those from Gp.HCD ( 15.1 +/- 5.3 versus 41.9 +/- 10.2%, 3.1 +/- 1.1versus 7.9 +/- 1.2% in Gp.NK and Gp.HCD aortic arch and thoracic aorta). Anti-macrophage staining area, the MMP1 or 2 and the nitrotyrosine positive area were decreased in Gp.NK., Conclusion: Pitavastatin retards the progression of atherosclerosis formation and it improves NO bioavailability by eNOS up-regulation and decrease of O(2)(-).
- Published
- 2004
- Full Text
- View/download PDF
14. Combined effect of testosterone and apocynin on nitric oxide and superoxide production in PMA-differentiated THP-1 cells.
- Author
-
Juliet PA, Hayashi T, Daigo S, Matsui-Hirai H, Miyazaki A, Fukatsu A, Funami J, Iguchi A, and Ignarro LJ
- Subjects
- Acetophenones administration & dosage, Aromatase Inhibitors, Cells, Cultured, Enzyme Inhibitors pharmacology, Fadrozole pharmacology, Humans, Macrophages drug effects, Male, NADPH Oxidases antagonists & inhibitors, Nitric Oxide Synthase Type II, Phosphoproteins metabolism, Reverse Transcriptase Polymerase Chain Reaction, Testosterone administration & dosage, Tetradecanoylphorbol Acetate, Acetophenones pharmacology, Macrophages metabolism, Nitric Oxide metabolism, Nitric Oxide Synthase biosynthesis, Superoxides metabolism, Testosterone pharmacology
- Abstract
Human inducible nitric oxide synthase (iNOS) is most readily observed in macrophages from patients with inflammatory diseases like atherosclerosis. The aim of the present study was to find out the combined effect of male sex hormone; testosterone and apocynin (NADPH oxidase inhibitor) on cytokine-induced iNOS production. THP-1 cells were differentiated into macrophages by phorbol myristate acetate (PMA). Expression of iNOS was induced by the addition of cytokine mixture? Testosterone was added at different concentrations (10(-6)-10(-12) M) with apocynin (1 mM). Testosterone (10(-8), 10(-10) M) inhibited NOx production in cytokine-added THP-1 cells which was further confirmed by quantikine assay of iNOS protein and RT-PCR analysis. Testosterone treatment decreased 40% of superoxide anion production. Testosterone showed inhibition of NADPH oxidase, especially expression of p67phox and p47phox (cytosol subunits). Addition of testosterone with apocynin further decreased the expression of p67phox and p47phox subunits of NADPH oxidase. The findings of the present study suggest that, testosterone; the male androgen plays an important role in the prevention of atherogenesis. Even though apocynin does not have any role on NO production, addition of apocynin together with testosterone is effective in suppressing iNOS activity.
- Published
- 2004
- Full Text
- View/download PDF
15. Gene transfer of endothelial NO synthase, but not eNOS plus inducible NOS, regressed atherosclerosis in rabbits.
- Author
-
Hayashi T, Sumi D, Juliet PA, Matsui-Hirai H, Asai-Tanaka Y, Kano H, Fukatsu A, Tsunekawa T, Miyazaki A, Iguchi A, and Ignarro LJ
- Subjects
- Acetylcholine, Adenoviridae genetics, Animals, Aorta, Abdominal metabolism, Aorta, Abdominal pathology, Arteriosclerosis metabolism, Arteriosclerosis pathology, Cholesterol metabolism, Dose-Response Relationship, Drug, Enzyme Inhibitors pharmacology, Genetic Vectors administration & dosage, Infusions, Intra-Arterial, Lipid Metabolism, Male, Models, Animal, Nitric Oxide metabolism, Nitric Oxide Synthase antagonists & inhibitors, Nitric Oxide Synthase metabolism, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, Nitroglycerin, Oxygen metabolism, Peroxynitrous Acid metabolism, Rabbits, Vasodilator Agents, omega-N-Methylarginine pharmacology, Arteriosclerosis therapy, Genetic Therapy methods, Nitric Oxide Synthase genetics, Transduction, Genetic methods
- Abstract
The effects of in vivo gene transfer of endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) genes on severe atherosclerosis were investigated in rabbits. The recombinant adenoviruses, Ad.eNOS and Ad.iNOS, which respectively express eNOS and iNOS, were constructed. Atherosclerosis was induced by a balloon injury followed by a high cholesterol diet for 12 weeks. The rabbits were divided into six groups: Gp cont (no treatment); Gp null (adenovirus sham-infected); Gp eNOS (Ad.eNOS); Gp iNOS (Ad.iNOS); Gp e+i (Ad.eNOS plus Ad.iNOS); and Gp heNOS (a high dose of Ad.eNOS). Examinations were carried out 7 days after gene transfer. Plasma lipid levels were not significantly changed, but transfection with Ad.eNOS (Gp eNOS and Gp heNOS) decreased the tissue cholesterol concentration and regressed atherosclerotic lesions. Vessels treated with Ad.iNOS (Gp iNOS and Gp e+i) showed iNOS staining in the atheroma, and slight staining at other parts of the vessels; those treated with Ad.eNOS showed eNOS staining in the endothelium and subintima, and slight staining at other parts. Ad.eNOS transfection, but not Ad.iNOS or Ad.eNOS+Ad.iNOS transfection, improved the impaired aortic endothelium-dependent relaxation (EDR) and basal NO-dependent response, increased tissue cyclic GMP (cGMP), and decreased the release of O2- from vessels. eNOS treatment showed a decreasing tendency in regions with peroxynitrite staining, MMP1 staining, and suspected apoptosis. In conclusion, in vivo gene transfer of eNOS, but not iNOS or eNOS plus iNOS, regressed atherosclerosis. The relations among NO, O2-, and peroxynitrite may be critical, and lipid resorption from the lesions may be responsible for the regression.
- Published
- 2004
- Full Text
- View/download PDF
16. 17beta-estradiol inhibits NADPH oxidase activity through the regulation of p47phox mRNA and protein expression in THP-1 cells.
- Author
-
Sumi D, Hayashi T, Matsui-Hirai H, Jacobs AT, Ignarro LJ, and Iguchi A
- Subjects
- Cell Line, Humans, Interferon-gamma pharmacology, NF-kappa B antagonists & inhibitors, RNA, Messenger analysis, Tumor Necrosis Factor-alpha pharmacology, Estradiol pharmacology, Gene Expression Regulation drug effects, NADPH Oxidases antagonists & inhibitors, Phosphoproteins genetics
- Abstract
In this report, we demonstrate that NADPH oxidase is activated by tumor necrosis factor-alpha (TNF-alpha) plus interferon-gamma (IFN-gamma) in human monocytic cells (THP-1 cells) differentiated with phorbol ester (PMA) and that physiological concentration of 17beta-estradiol inhibits NADPH oxidase activity in THP-1 cells stimulated with TNF-alpha plus IFN-gamma. This effect is mediated by estrogen receptor based on estrogen receptor antagonist (ICI 182, 780) that diminishes inhibition by 17beta-estradiol. This inhibition is specific in 17beta-estradiol because 17alpha-estradiol, testosterone and progesterone do not inhibit NADPH oxidase activity. Activation of NADPH oxidase induced by TNF-alpha plus IFN-gamma is caused by up-regulation of p47(phox) (cytosolic component of NADPH oxidase) expression. 17beta-Estradiol prevents the up-regulation of p47(phox) mRNA and protein expression. This prevention of p47(phox) expression depends on the inhibition of NF-kappaB activation. Our results implicate that 17beta-estradiol has an anti-atherosclerotic effects through the improvement of nitric oxide (NO) bioavailability caused by the regulation of superoxide (O(2)(-)) production.
- Published
- 2003
- Full Text
- View/download PDF
17. Sarpogrelate HCl, a selective 5-HT2A antagonist, retards the progression of atherosclerosis through a novel mechanism.
- Author
-
Hayashi T, Sumi D, Matsui-Hirai H, Fukatsu A, Arockia Rani P J, Kano H, Tsunekawa T, and Iguchi A
- Subjects
- Acetylcholine administration & dosage, Animals, Antioxidants therapeutic use, Aorta, Thoracic drug effects, Aorta, Thoracic pathology, Aorta, Thoracic physiopathology, Biomarkers blood, Blood Proteins metabolism, Cholesterol, HDL blood, Coronary Artery Disease etiology, Coronary Artery Disease metabolism, Cyclic GMP metabolism, Disease Models, Animal, Disease Progression, Dose-Response Relationship, Drug, Endothelium, Vascular drug effects, Endothelium, Vascular pathology, Endothelium, Vascular physiopathology, Hypercholesterolemia drug therapy, Hypercholesterolemia etiology, Hypercholesterolemia metabolism, Male, Matrix Metalloproteinase 1 drug effects, Matrix Metalloproteinase 1 metabolism, Matrix Metalloproteinase 2 drug effects, Matrix Metalloproteinase 2 metabolism, Models, Cardiovascular, Myocardial Contraction drug effects, Myocardial Contraction physiology, Myocytes, Smooth Muscle drug effects, Myocytes, Smooth Muscle metabolism, Nitric Oxide Synthase drug effects, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, RNA, Messenger drug effects, RNA, Messenger metabolism, Rabbits, Treatment Outcome, Vasodilator Agents administration & dosage, Vitamin E therapeutic use, Coronary Artery Disease drug therapy, Serotonin Antagonists therapeutic use, Succinates therapeutic use
- Abstract
Although sarpogrelate HCl is widely used for the prevention of arterial thrombosis, its effect on atherosclerosis is unknown. Accordingly, we here investigated the effects of sarpogrelate HCl on a rabbit model of atherosclerosis. Male rabbits were fed a 0.5% cholesterol diet (HCD) (Gp 1), HCD with vitamin E (Gp 2), HCD with vitamin E and sarpogrelate (Gp 3), or HCD with sarpogrelate alone (Gp 4) for 8 weeks. The atherosclerotic area was decreased by feeding of vitamin E and sarpogrelate (16.9+/-2.0% in Gp 1 vs. 8.2+/-2.0% in Gp 3). Tone-related basal NO release was higher in Gps 3 and 4. Acetylcholine-induced relaxation tended to be improved in Gp 3. The amount of eNOS mRNA was increased in Gp 4, and aortic cyclic GMP concentration showed the same tendency. O(2)(-) release tended to be decreased in Gps 2 and 3. The matrix metalloproteinase-1 (MMP-1)-positive area was decreased, and the percentage ratio of cell numbers of smooth muscle cells/macrophages in the plaque was increased in Gp 3. The results demonstrated that sarpogrelate HCl retards the progression of atherosclerosis in rabbits, and that this effect is enhanced by concomitant administration of vitamin E. Although upregulation of eNOS may play a role as one of the underlying mechanisms, our results suggest that an additional mechanism-possibly involving the antiproliferative effects of sarpogrelate HCl on smooth muscle cells and macrophages-may also play an important role.
- Published
- 2003
- Full Text
- View/download PDF
18. Plasma adiponectin plays an important role in improving insulin resistance with glimepiride in elderly type 2 diabetic subjects.
- Author
-
Tsunekawa T, Hayashi T, Suzuki Y, Matsui-Hirai H, Kano H, Fukatsu A, Nomura N, Miyazaki A, and Iguchi A
- Subjects
- Adiponectin, Aged, Dinoprost blood, Female, Humans, Male, Middle Aged, Osmolar Concentration, Plasminogen Activator Inhibitor 1 blood, Tumor Necrosis Factor-alpha analysis, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 physiopathology, Dinoprost analogs & derivatives, Hypoglycemic Agents therapeutic use, Insulin Resistance, Intercellular Signaling Peptides and Proteins, Proteins analysis, Sulfonylurea Compounds therapeutic use
- Abstract
Objective: We investigated the effect of glimepiride, a third-generation sulfonylurea hypoglycemic agent, on insulin resistance in elderly patients with type 2 diabetes, in connection with plasma adiponectin and 8-epi-prostagrandin F2alpha (8-epi-PGF2alpha), an oxidative stress marker., Research Design and Methods: A total of 17 elderly patients with type 2 diabetes received 12 weeks of treatment with glimepiride. Homeostasis assessment model of insulin resistance (HOMA-IR), homeostasis assessment model of beta-cell function, HbA(1c), C-peptide in 24-h pooled urine (urine CPR), and plasma concentrations of 8-epi-PGF2alpha, tumor necrosis factor-alpha (TNF-alpha), plasminogen activator inhibitor type 1, and adiponectin were measured at various times. The metabolic clearance rate of glucose (MCR-g) was also assessed by a hyperinsulinemic-euglycemic clamp., Results: After 8 weeks of glimepiride treatment, significant reductions were observed in HbA(1c) (from 8.4 +/- 1.9 to 6.9 +/- 1.0%), HOMA-IR (from 2.54 +/- 2.25 to 1.69 +/- 0.95%), and plasma TNF-alpha concentrations (from 4.0 +/- 2.0 to 2.6 +/- 2.5 pg/ml). MCR-g was significantly increased from 3.92 +/- 1.09 to 5.73 +/- 1.47 mg. kg(-1). min(-1). Plasma adiponectin increased from 6.61 +/- 3.06 to 10.2 +/- 7.14 micro g/ml. In control subjects, who maintained conventional treatment, no significant changes were observed in any of these markers., Conclusions: Glimepiride remarkably improved insulin resistance, suggested by a significant reduction in HOMA-IR, an increase in MCR-g, and a reduction in HbA(1c) without changing extrapancreatic beta-cell function and urine CPR. Increased plasma adiponectin and decreased plasma TNF-alpha may underlie the improvement of insulin resistance with glimepiride.
- Published
- 2003
- Full Text
- View/download PDF
19. In vivo assessment of adenoviral vector-mediated gene expression of dopamine D(2) receptors in the rat striatum by positron emission tomography.
- Author
-
Umegaki H, Ishiwata K, Ogawa O, Ingram DK, Roth GS, Yoshimura J, Oda K, Matsui-Hirai H, Ikari H, Iguchi A, and Senda M
- Subjects
- Adenoviridae genetics, Animals, Binding, Competitive drug effects, Corpus Striatum drug effects, Dopamine Antagonists, Gene Expression Regulation drug effects, Genetic Therapy instrumentation, Genetic Therapy methods, Male, Neurons drug effects, Raclopride, Rats, Rats, Inbred F344, Receptors, Dopamine D2 drug effects, Receptors, Dopamine D2 genetics, Tomography, Emission-Computed, Binding, Competitive physiology, Corpus Striatum diagnostic imaging, Gene Expression Regulation physiology, Genetic Vectors, Neurons metabolism, Receptors, Dopamine D2 metabolism
- Abstract
For functional assessment of gene therapy in experimental animals, in vivo assessment of transferred genes will provide a major advance over an in vitro analysis which must be done post-hoc. In the current study we conducted positron emission tomography (PET) analysis in rats following injection of the adenoviral vector encoding the cDNA for the rat dopamine D(2) receptors (D(2)R) (AdCMV.DopD(2)R) into rat brain to provide a quantitative evaluation of D(2)R overexpression. Quantitative measurements as well as images by PET and ex vivo autoradiography demonstrated the significant increase of D(2)R binding of [(11)C]raclopride, a specific D(2)R radioligand, in the AdCMV.DopD(2)R-injected rat striatum 2 or 3 days after vector injection. Longitudinal in vivo assessment of the gene expression by PET demonstrated decreased binding of [(11)C]raclopride with time, which was in agreement with the observation in a cross-sectional autoradiographic study. The results of the current study demonstrate that PET can be used for longitudinal in vivo assessment of D(2)R expression mediated by adenoviral vector in rat brain., (Copyright 2002 Wiley-Liss, Inc.)
- Published
- 2002
- Full Text
- View/download PDF
20. Anti-atherosclerotic effect of beta-blocker with nitric oxide-releasing action on the severe atherosclerosis.
- Author
-
Thakur NK, Hayashi T, Sumi D, Kano H, Matsui-Hirai H, Tsunekawa T, and Iguchi A
- Subjects
- Adrenergic beta-Antagonists pharmacology, Animals, Aorta, Thoracic chemistry, Aorta, Thoracic metabolism, Aorta, Thoracic pathology, Arteriosclerosis etiology, Atenolol pharmacology, Atenolol therapeutic use, Blood Pressure drug effects, Cholesterol analysis, Cholesterol, Dietary adverse effects, Endothelium, Vascular metabolism, Endothelium, Vascular physiopathology, Heart Rate drug effects, Isosorbide Dinitrate pharmacology, Isosorbide Dinitrate therapeutic use, Male, Muscle Relaxation drug effects, Nitric Oxide deficiency, Nitric Oxide Donors pharmacology, Nitric Oxide Synthase antagonists & inhibitors, Nitric Oxide Synthase genetics, Nitroglycerin pharmacology, Nitroglycerin therapeutic use, Propanolamines pharmacology, RNA, Messenger drug effects, RNA, Messenger metabolism, Rabbits, Reverse Transcriptase Polymerase Chain Reaction, Vasodilator Agents pharmacology, Vasodilator Agents therapeutic use, Adrenergic beta-Antagonists therapeutic use, Arteriosclerosis drug therapy, Nitric Oxide Donors therapeutic use, Propanolamines therapeutic use
- Abstract
It is not completely understood whether nitric oxide donors and beta-adrenoceptor antagonists have anti-atherosclerotic effects. The anti-atherosclerotic effects of beta-adrenergic receptor antagonists and nitric oxide donors on severe atherosclerosis induced by cholesterol and inhibition of nitric oxide synthesis were determined. Six groups of New Zealand white male rabbits were treated for 10 weeks, under the following regimens: group I: high-cholesterol diet (HCD) (standard diet plus 0.5% cholesterol); group II: HCD plus N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase; group III: HCD plus L-NAME and isosorbide dinitrate; group IV: HCD plus L-NAME and nitroglycerin; group V: HCD plus L-NAME and nipradilol (beta-blocker with nitric oxide-releasing action); and group VI: HCD plus L-NAME and atenolol (beta-blocker). Serum lipid levels did not differ among the six groups. Blood pressure and heart rates were slightly decreased in groups V and VI. The atherosclerotic area and aortic cholesterol increased in L-NAME-treated animals but not in animals in group V. The endothelium-dependent relaxations and basal nitric oxide release were impaired in the L-NAME treatment group, though not in group V, in comparison with those in group I. cGMP in the aorta was increased in groups III, IV, and V as compared with that in group II. Endothelial nitric oxide synthase mRNA was decreased in the aortae of L-NAME-treated rabbits and increased in aortae in group V, in comparison with that in group I. Conclusively, nipradilol, beta-blocker with nitric oxide-releasing action, in contrast to the other beta-blockers and nitric oxide donors, showed a successful anti-atherosclerotic effect through the restoration of nitric oxide bioavailability and possible interaction with oxygen radicals.
- Published
- 2002
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.