13 results on '"Inaba, Shinji"'
Search Results
2. Prevention of Vascular Injury by Combination of an AT1 Receptor Blocker, Olmesartan, With Various Calcium Antagonists
- Author
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Inaba, Shinji, primary, Iwai, Masaru, additional, Tomono, Yumiko, additional, Senba, Izumi, additional, Furuno, Megumi, additional, Kanno, Harumi, additional, Okayama, Hideki, additional, Mogi, Masaki, additional, Higaki, Jitsuo, additional, and Horiuchi, Masatsugu, additional
- Published
- 2008
- Full Text
- View/download PDF
3. Temporary Treatment With AT1 Receptor Blocker, Valsartan, From Early Stage of Hypertension Prevented Vascular Remodeling.
- Author
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Inaba, Shinji, Iwai, Masaru, Furuno, Megumi, Kanno, Harumi, Senba, Izumi, Okayama, Hideki, Mogi, Masaki, Higaki, Jitsuo, and Horiuchi, Masatsugu
- Subjects
VALSARTAN ,ANGIOTENSIN II ,HYPERTENSION ,THERAPEUTICS ,BLOOD pressure ,INFLAMMATION ,OXIDATIVE stress ,TRANSGENIC mice - Abstract
BackgroundThe present study examined the inhibitory action of temporary treatment with an angiotensin type 1 (AT
1 ) receptor blocker (ARB) on vascular remodeling using hypertensive mice with overexpression of the human renin (hRN) and angiotensinogen (hANG) genes.MethodshRN/hANG transgenic mice (hRN/hANG-Tg) were treated with an ARB, valsartan, from 4 weeks of age. In some mice, valsartan treatment was stopped at 8 weeks of age (temporary treatment). Inflammatory vascular injury was induced by polyethylene-cuff placement around the femoral artery at the age of 10 weeks.ResultsCompared with wild-type (WT) mice, hRN/hANG-Tg showed higher blood pressure (BP) and enhancement of oxidative stress and medial thickening even before cuff placement. Inflammatory vascular remodeling and oxidative stress after cuff placement were further enhanced in hRN/hANG-Tg. Temporary treatment with valsartan continuously lowered BP even after cessation of administration, and inhibited these changes. In contrast, administration of hydralazine lowered BP to a similar level to that with valsartan, but did not inhibit medial thickening and inflammatory vascular remodeling. In contrast to the valsartan treatment, BP immediately increased to the untreated level after cessation of hydralazine.ConclusionsThese results indicate that temporary ARB treatment leads to prolonged effect of BP lowering and prevents vascular remodeling in hypertensive mice induced by activation of the human renin-angiotensin system. The inhibitory action of valsartan is not due to the BP lowering but is at least in part due to a decrease in oxidative stress and inflammation.American Journal of Hypertension (2011). doi:10.1038/ajh.2011.6 [ABSTRACT FROM AUTHOR]- Published
- 2011
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- View/download PDF
4. Nifedipine, a Calcium-Channel Blocker, Attenuated Glucose Intolerance and White Adipose Tissue Dysfunction in Type 2 Diabetic KK-Ay Mice.
- Author
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Iwai, Masaru, Kanno, Harumi, Inaba, Shinji, Senba, Izumi, Sone, Hisako, Nakaoka, Hirotomo, and Horiuchi, Masatsugu
- Subjects
PEOPLE with diabetes ,NIFEDIPINE ,ADIPOSE tissues ,INSULIN resistance ,OXIDATIVE stress - Abstract
BackgroundTo explore the metabolic actions of nifedipine on diabetes, we examined glucose intolerance and white adipose tissue changes in type 2 diabetic KK-A
y mice.MethodsMale KK-Ay mice were treated with nifedipine (1.5 mg/kg/day in lab chow) for 5 weeks, which did not affect blood pressure or feeding of KK-Ay mice.ResultsAfter treatment with nifedipine, body weight tended to decrease and the weight of white adipose tissue was reduced. Without food restriction, nifedipine decreased plasma insulin level, while plasma glucose level tended to decrease. In oral glucose tolerance test, nifedipine suppressed the increase in glucose level after a glucose load without affecting plasma insulin concentration. Nifedipine also improved the result of insulin tolerance test. In white adipose tissue, nifedipine increased adipocyte number and the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and adipocyte fatty acid-binding protein related to adipocyte differentiation. In addition, expression of adiponectin, insulin receptor, insulin receptor substrate-1, and glucose transporter type-4 was also increased by nifedipine. Nifedipine also increased the expression of NO synthase in white adipose tissue. Nifedipine did not affect expression of angiotensin II type 1 (AT1 ) and type 2 (AT2 ) receptors in white adipose tissue. Such changes in white adipose tissue were apparent in retroperitoneal adipose tissue. Nifedipine did not change the expression of angiotensin receptors, renin receptor, and angiotensinogen in white adipose tissue. Moreover, nifedipine attenuated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and increased superoxide dismutase (SOD) activity in white adipose tissue.ConclusionThese results suggest that nifedipine can enhance insulin sensitivity and reduce white adipose tissue, possibly related to stimulation of adipocyte differentiation.American Journal of Hypertension (2011). doi:10.1038/ajh.2010.198 [ABSTRACT FROM AUTHOR]- Published
- 2011
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- View/download PDF
5. AT2 Receptor Deficiency Attenuates Adipocyte Differentiation and Decreases Adipocyte Number in Atherosclerotic Mice.
- Author
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Iwai, Masaru, Tomono, Yumiko, Inaba, Shinji, Kanno, Harumi, Senba, Izumi, Mogi, Masaki, and Horiuchi, Masatsugu
- Subjects
FAT cells ,ATHEROSCLEROTIC plaque ,LABORATORY mice ,ADIPOSE tissues ,APOLIPOPROTEINS ,FATTY acids - Abstract
BackgroundPrevious reports indicated that blockade of AT
1 receptor stimulation attenuated adipocyte dysfunction. However, the effects of AT2 receptor stimulation on adipose tissue were not yet clear. In the present study, we examined the adipose tissue dysfunction in atherosclerotic apolipoprotein E knockout (ApoEKO) mice with AT2 receptor deficiency.MethodsMale ApoEKO and AT2 receptor/ApoE knockout (AT2 /ApoEKO) mice at 6 weeks of age were treated with a normal diet or a high-cholesterol diet (HCD: 1.25% cholesterol). Markers for adipocyte differentiation and inflammation in adipose tissue were assayed with real-time reverse-transcription-PCR and western blot.ResultsCompared with ApoEKO mice, AT2 /ApoEKO mice with a normal diet showed only a decrease in expression of adiponectin and CCAAT/enhancer binding protein δ (C/EBPδ) in epididymal adipose tissue without changes in body weight, adipose tissue weight, and adipocyte number even at 6 months of age. After HCD for 4 weeks, the weight of both epididymal and retroperitoneal adipose tissue in AT2 /ApoEKO mice was greater than that in ApoEKO mice without a change in body weight. Plasma concentrations of cholesterol and fatty acids were higher in AT2 /ApoEKO mice than in ApoEKO mice. In adipose tissue of AT2 /ApoEKO mice, the adipocyte number was decreased and the expression of peroxisome proliferator–activated receptor γ (PPARγ), C/EBPα, and aP2 was lower than that in ApoEKO mice, in association with an increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.ConclusionsThese results suggest that AT2 receptor stimulation in adipose tissue is involved in the improvement of adipocyte differentiation and adipose tissue dysfunction in atherosclerotic model.American Journal of Hypertension 2009; doi:10.1038/ajh.2009.85American Journal of Hypertension 2009; 22, 7, 784–791. doi:10.1038/ajh.2009.85 [ABSTRACT FROM AUTHOR]- Published
- 2009
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- View/download PDF
6. Prevention of Vascular Injury by Combination of an AT1 Receptor Blocker, Olmesartan, With Various Calcium Antagonists.
- Author
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Inaba, Shinji, Iwai, Masaru, Tomono, Yumiko, Senba, Izumi, Furuno, Megumi, Kanno, Harumi, Okayama, Hideki, Mogi, Masaki, Higaki, Jitsuo, and Horiuchi, Masatsugu
- Subjects
THERAPEUTICS ,HYPERTENSION ,CARDIOVASCULAR diseases ,CALCIUM antagonists ,POLYETHYLENE ,FEMORAL artery - Abstract
BackgroundA combination of different types of antihypertensive drugs is widely used for the treatment of hypertension. We examined the inhibitory effects of a combination of an AT
1 receptor blocker (ARB), olmesartan, with various calcium channel blockers (CCBs) on inflammatory vascular remodeling.MethodsInflammatory vascular remodeling was induced by polyethylene-cuff placement around the femoral artery of C57BL/6J mice at 10 weeks of age. Olmesartan (0.5 mg/kg/day) was administered intraperitoneally using an osmotic minipump. CCBs (nifedipine 1.0 mg/kg/day, amlodipine 0.1 mg/kg/day, azelnidipine 0.1 mg/kg/day), and hydrochlorothiazide (HCTZ 0.5 mg/kg/day) were administered orally.ResultsIn the injured artery, superoxide anion production and expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p47phox and Rac-1 were markedly increased, together with expression of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor (TNF)-α. Administration of a single drug alone at each concentration did not significantly inhibit these changes in the injured artery. However, a combination of olmesartan with various CCBs inhibited neointimal formation as well as oxidative stress and inflammatory markers in the injured artery. Moreover, among these CCBs, inhibition of these markers by olmesartan with azelnidipine was stronger than that caused by a combination with other CCBs. On the other hand, a combination of subeffective doses of olmesartan and HCTZ did not significantly affect vascular changes after cuff placement.ConclusionsThese results suggest that the combination of ARB with CCB synergistically inhibits vascular remodeling and that the inhibitory actions of ARB on vascular remodeling may vary depending on the combined CCB.American Journal of Hypertension (2009). doi:10.1038/ajh.2008.344American Journal of Hypertension (2009); 22, 2, 145–150. doi:10.1038/ajh.2008.344 [ABSTRACT FROM AUTHOR]- Published
- 2009
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7. Blockade of AT1 Receptor Improves Adipocyte Differentiation in Atherosclerotic and Diabetic Models.
- Author
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Tomono, Yumiko, Iwai, Masaru, Inaba, Shinji, Mogi, Masaki, and Horiuchi, Masatsugu
- Subjects
FAT cells ,CELL differentiation ,ATHEROSCLEROSIS ,PEOPLE with diabetes ,ANGIOTENSIN-receptor blockers ,BIOMARKERS - Abstract
BACKGROUND The roles of the angiotensin (Ang) II type 1 (AT
1 ) receptor in the changes in white adipose tissue were explored in an animal model of atherosclerosis using apolipoprotein E-deficient (ApoEKO) mice. METHODS Apolipoprotein E-deficient (ApoEKO) mice and KK-Ay mice were used. Expression of markers for adipocyte differentiation and inflammation was determined by real-time reverse-transcription polymerase chain reaction. RESULTS Adipose tissue weight and adipocyte size in epididymal white adipose tissue were increased in ApoEKO mice and KK-Ay mice. In the adipose tissue of these models, expression of adiponectin and peroxisome proliferator-activated receptor-γ (PPARγ), which induce adipocyte differentiation, and expression of transcription factors of adipocyte differentiation, such as CCAAT-enhancer-binding protein-α (C/EBPα) and aP2, were decreased. Expression of inflammatory markers and nicotinamide adenine dinucleotide phosphate oxidase subunits was also increased. Deletion of AT1 a receptor in ApoEKO mice and administration of an AT1 receptor blocker, valsartan, to KK-Ay mice reduced epididymal adipose tissue weight and adipocyte size significantly. Blockade of the AT1 receptor also reduced the expression of inflammatory chemokines and oxidative stress markers. Moreover, AT1 a receptor deletion in ApoEKO mice and AT1 receptor blockade in KK-Ay mice prevented the decrease in expression of adiponectin, PPARγ, C/EBPα, and aP2. Valsartan also increased glucose uptake induced by insulin in adipose tissue of KK-Ay mice. CONCLUSIONS These results suggest that enlargement and weakened differentiation of adipocytes are observed in atherosclerosis and diabetes, and that AT1 receptor blockade prevented adipocyte enlargement and promoted adipocyte differentiation in these models. [ABSTRACT FROM AUTHOR]- Published
- 2008
- Full Text
- View/download PDF
8. Attenuation of Monocyte Chemoattractant Protein-1 Expression Via Inhibition of Nuclear Factor-κB Activity in Inflammatory Vascular Injury
- Author
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Gao, Xinyu, Iwai, Masaru, Inaba, Shinji, Tomono, Yumiko, Kanno, Harumi, Mogi, Masaki, and Horiuchi, Masatsugu
- Subjects
BLOOD vessels ,CALCIUM antagonists ,NIFEDIPINE ,SMOOTH muscle - Abstract
Background: The effect of a calcium channel blocker (CCB) on the expression of monocyte chemoattractant protein (MCP)-1 was explored in inflammatory vascular injury, focusing on the role of nuclear factor (NF)-κB. Methods: Vascular injury was induced by cuff placement. Expression of MCP-1 was determined by real-time RT-PCR. NF-κB expression and its activity were detected by Western blot and electrophoretic mobility shift assay. Results: Polyethylene cuff placement around the mouse femoral artery increased MCP-1 expression, together with proliferation of vascular smooth muscle cells and neointimal formation in the injured artery. The content of NF-κB was decreased in the cytosolic fraction but increased in the nuclear fraction prepared from the injured artery. In the nuclear fraction, the binding activity of NF-κB to the promoter region of MCP-1 was markedly increased. On the other hand, IκB content in the cytosolic fraction was decreased in the injured artery after cuff placement, accompanied by an increase in IκB kinase (IKK) phosphorylation. Treatment of mice with a CCB, nifedipine, at a dose of 5 mg/kg/day, significantly decreased vascular smooth muscle cell proliferation and neointimal formation without affecting blood pressure. This dose of nifedipine inhibited the increase in MCP-1 expression in the injured artery. Moreover, nifedipine reduced the nuclear content and DNA-binding activity of NF-κB in the injured artery. In contrast, the decrease in IκB content and the increase in IKK phosphorylation in the cytosolic fraction were attenuated by nifedipine. Conclusions: These results indicate that MCP-1 expression in inflammatory vascular injury is regulated by activation of NF-κB. The results also suggest that nifedipine attenuates MCP-1 expression in the injured artery via inhibition of the nuclear translocation and DNA-binding activity of NF-κB, and thereby improves vascular remodeling. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
9. Nifedipine, a calcium-channel blocker, attenuated glucose intolerance and white adipose tissue dysfunction in type 2 diabetic KK-A(y) mice.
- Author
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Iwai M, Kanno H, Inaba S, Senba I, Sone H, Nakaoka H, and Horiuchi M
- Subjects
- Adipocytes metabolism, Adipogenesis drug effects, Adiponectin metabolism, Adipose Tissue, White metabolism, Adipose Tissue, White physiopathology, Animals, Blood Glucose metabolism, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 physiopathology, Disease Models, Animal, Fatty Acid-Binding Proteins metabolism, Glucose Tolerance Test, Glucose Transporter Type 4 metabolism, Insulin blood, Insulin Receptor Substrate Proteins metabolism, Male, Mice, Mice, Inbred Strains, NADPH Oxidases metabolism, Nitric Oxide Synthase metabolism, Oxidative Stress drug effects, PPAR gamma metabolism, Receptors, Angiotensin metabolism, Superoxide Dismutase metabolism, Time Factors, Weight Loss, Adipocytes drug effects, Adipose Tissue, White drug effects, Blood Glucose drug effects, Calcium Channel Blockers pharmacology, Diabetes Mellitus, Type 2 drug therapy, Insulin Resistance, Nifedipine pharmacology
- Abstract
Background: To explore the metabolic actions of nifedipine on diabetes, we examined glucose intolerance and white adipose tissue changes in type 2 diabetic KK-A(y) mice., Methods: Male KK-A(y) mice were treated with nifedipine (1.5 mg/kg/day in lab chow) for 5 weeks, which did not affect blood pressure or feeding of KK-A(y) mice., Results: After treatment with nifedipine, body weight tended to decrease and the weight of white adipose tissue was reduced. Without food restriction, nifedipine decreased plasma insulin level, while plasma glucose level tended to decrease. In oral glucose tolerance test, nifedipine suppressed the increase in glucose level after a glucose load without affecting plasma insulin concentration. Nifedipine also improved the result of insulin tolerance test. In white adipose tissue, nifedipine increased adipocyte number and the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and adipocyte fatty acid-binding protein related to adipocyte differentiation. In addition, expression of adiponectin, insulin receptor, insulin receptor substrate-1, and glucose transporter type-4 was also increased by nifedipine. Nifedipine also increased the expression of NO synthase in white adipose tissue. Nifedipine did not affect expression of angiotensin II type 1 (AT₁) and type 2 (AT₂) receptors in white adipose tissue. Such changes in white adipose tissue were apparent in retroperitoneal adipose tissue. Nifedipine did not change the expression of angiotensin receptors, renin receptor, and angiotensinogen in white adipose tissue. Moreover, nifedipine attenuated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and increased superoxide dismutase (SOD) activity in white adipose tissue., Conclusion: These results suggest that nifedipine can enhance insulin sensitivity and reduce white adipose tissue, possibly related to stimulation of adipocyte differentiation.
- Published
- 2011
- Full Text
- View/download PDF
10. AT2 receptor deficiency attenuates adipocyte differentiation and decreases adipocyte number in atherosclerotic mice.
- Author
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Iwai M, Tomono Y, Inaba S, Kanno H, Senba I, Mogi M, and Horiuchi M
- Subjects
- Adipose Tissue drug effects, Adipose Tissue pathology, Angiotensin II Type 1 Receptor Blockers pharmacology, Angiotensin II Type 2 Receptor Blockers, Animals, Apolipoproteins E genetics, Atherosclerosis physiopathology, Cell Count, Cell Differentiation physiology, Cholesterol, Dietary administration & dosage, Insulin Receptor Substrate Proteins metabolism, Male, Mice, Mice, Knockout, NADPH Oxidases metabolism, Receptor, Angiotensin, Type 2 physiology, Tetrazoles pharmacology, Valine analogs & derivatives, Valine pharmacology, Valsartan, Adipocytes physiology, Atherosclerosis pathology, Receptor, Angiotensin, Type 2 deficiency
- Abstract
Background: Previous reports indicated that blockade of AT(1) receptor stimulation attenuated adipocyte dysfunction. However, the effects of AT(2) receptor stimulation on adipose tissue were not yet clear. In the present study, we examined the adipose tissue dysfunction in atherosclerotic apolipoprotein E knockout (ApoEKO) mice with AT(2) receptor deficiency., Methods: Male ApoEKO and AT(2) receptor/ApoE knockout (AT(2)/ApoEKO) mice at 6 weeks of age were treated with a normal diet or a high-cholesterol diet (HCD: 1.25% cholesterol). Markers for adipocyte differentiation and inflammation in adipose tissue were assayed with real-time reverse-transcription-PCR and western blot., Results: Compared with ApoEKO mice, AT(2)/ApoEKO mice with a normal diet showed only a decrease in expression of adiponectin and CCAAT/enhancer binding protein delta (C/EBPdelta) in epididymal adipose tissue without changes in body weight, adipose tissue weight, and adipocyte number even at 6 months of age. After HCD for 4 weeks, the weight of both epididymal and retroperitoneal adipose tissue in AT(2)/ApoEKO mice was greater than that in ApoEKO mice without a change in body weight. Plasma concentrations of cholesterol and fatty acids were higher in AT(2)/ApoEKO mice than in ApoEKO mice. In adipose tissue of AT(2)/ApoEKO mice, the adipocyte number was decreased and the expression of peroxisome proliferator-activated receptor gamma (PPARgamma), C/EBPalpha, and aP2 was lower than that in ApoEKO mice, in association with an increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity., Conclusions: These results suggest that AT(2) receptor stimulation in adipose tissue is involved in the improvement of adipocyte differentiation and adipose tissue dysfunction in atherosclerotic model.
- Published
- 2009
- Full Text
- View/download PDF
11. Prevention of vascular injury by combination of an AT1 receptor blocker, olmesartan, with various calcium antagonists.
- Author
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Inaba S, Iwai M, Tomono Y, Senba I, Furuno M, Kanno H, Okayama H, Mogi M, Higaki J, and Horiuchi M
- Subjects
- Amlodipine pharmacology, Animals, Azetidinecarboxylic Acid analogs & derivatives, Azetidinecarboxylic Acid pharmacology, Chemokine CCL2 biosynthesis, Dihydropyridines pharmacology, Drug Synergism, Femoral Artery injuries, Ligation, Male, Mice, Mice, Inbred C57BL, NADPH Oxidases biosynthesis, Neuropeptides biosynthesis, Nifedipine pharmacology, Superoxides metabolism, Tumor Necrosis Factor-alpha biosynthesis, Tunica Intima drug effects, rac GTP-Binding Proteins biosynthesis, rac1 GTP-Binding Protein, Angiotensin II Type 1 Receptor Blockers pharmacology, Calcium Channel Blockers pharmacology, Femoral Artery drug effects, Imidazoles pharmacology, Tetrazoles pharmacology
- Abstract
Background: A combination of different types of antihypertensive drugs is widely used for the treatment of hypertension. We examined the inhibitory effects of a combination of an AT(1) receptor blocker (ARB), olmesartan, with various calcium channel blockers (CCBs) on inflammatory vascular remodeling., Methods: Inflammatory vascular remodeling was induced by polyethylene-cuff placement around the femoral artery of C57BL/6J mice at 10 weeks of age. Olmesartan (0.5 mg/kg/day) was administered intraperitoneally using an osmotic minipump. CCBs (nifedipine 1.0 mg/kg/day, amlodipine 0.1 mg/kg/day, azelnidipine 0.1 mg/kg/day), and hydrochlorothiazide (HCTZ 0.5 mg/kg/day) were administered orally., Results: In the injured artery, superoxide anion production and expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p47(phox) and Rac-1 were markedly increased, together with expression of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor (TNF)-alpha. Administration of a single drug alone at each concentration did not significantly inhibit these changes in the injured artery. However, a combination of olmesartan with various CCBs inhibited neointimal formation as well as oxidative stress and inflammatory markers in the injured artery. Moreover, among these CCBs, inhibition of these markers by olmesartan with azelnidipine was stronger than that caused by a combination with other CCBs. On the other hand, a combination of subeffective doses of olmesartan and HCTZ did not significantly affect vascular changes after cuff placement., Conclusions: These results suggest that the combination of ARB with CCB synergistically inhibits vascular remodeling and that the inhibitory actions of ARB on vascular remodeling may vary depending on the combined CCB.
- Published
- 2009
- Full Text
- View/download PDF
12. Blockade of AT1 receptor improves adipocyte differentiation in atherosclerotic and diabetic models.
- Author
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Tomono Y, Iwai M, Inaba S, Mogi M, and Horiuchi M
- Subjects
- Adipocytes, White cytology, Adipocytes, White drug effects, Adiponectin genetics, Angiotensin II Type 1 Receptor Blockers pharmacology, Animals, Apolipoproteins E genetics, Atherosclerosis drug therapy, Atherosclerosis genetics, Cell Differentiation physiology, Diabetes Mellitus, Type 2 genetics, Diabetic Angiopathies drug therapy, Diabetic Angiopathies genetics, Disease Models, Animal, Gene Deletion, Gene Expression physiology, Male, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Obesity genetics, Obesity physiopathology, PPAR gamma genetics, Receptor, Angiotensin, Type 1 metabolism, Tetrazoles pharmacology, Valine analogs & derivatives, Valine pharmacology, Valsartan, Adipocytes, White physiology, Atherosclerosis physiopathology, Diabetes Mellitus, Type 2 physiopathology, Diabetic Angiopathies physiopathology, Receptor, Angiotensin, Type 1 genetics
- Abstract
Background: The roles of the angiotensin (Ang) II type 1 (AT(1)) receptor in the changes in white adipose tissue were explored in an animal model of atherosclerosis using apolipoprotein E-deficient (ApoEKO) mice., Methods: Apolipoprotein E-deficient (ApoEKO) mice and KK-A(y) mice were used. Expression of markers for adipocyte differentiation and inflammation was determined by real-time reverse-transcription polymerase chain reaction., Results: Adipose tissue weight and adipocyte size in epididymal white adipose tissue were increased in ApoEKO mice and KK-A(y) mice. In the adipose tissue of these models, expression of adiponectin and peroxisome proliferator-activated receptor-gamma (PPARgamma), which induce adipocyte differentiation, and expression of transcription factors of adipocyte differentiation, such as CCAAT-enhancer-binding protein-alpha (C/EBPalpha) and aP2, were decreased. Expression of inflammatory markers and nicotinamide adenine dinucleotide phosphate oxidase subunits was also increased. Deletion of AT(1)a receptor in ApoEKO mice and administration of an AT(1) receptor blocker, valsartan, to KK-A(y) mice reduced epididymal adipose tissue weight and adipocyte size significantly. Blockade of the AT(1) receptor also reduced the expression of inflammatory chemokines and oxidative stress markers. Moreover, AT(1)a receptor deletion in ApoEKO mice and AT(1) receptor blockade in KK-A(y) mice prevented the decrease in expression of adiponectin, PPARgamma, C/EBPalpha, and aP2. Valsartan also increased glucose uptake induced by insulin in adipose tissue of KK-A(y) mice., Conclusions: These results suggest that enlargement and weakened differentiation of adipocytes are observed in atherosclerosis and diabetes, and that AT(1) receptor blockade prevented adipocyte enlargement and promoted adipocyte differentiation in these models.
- Published
- 2008
- Full Text
- View/download PDF
13. Attenuation of monocyte chemoattractant protein-1 expression via inhibition of nuclear factor-kappaB activity in inflammatory vascular injury.
- Author
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Gao X, Iwai M, Inaba S, Tomono Y, Kanno H, Mogi M, and Horiuchi M
- Subjects
- Animals, Blood Pressure drug effects, Calcium Channel Blockers pharmacology, Cell Nucleus drug effects, Cell Nucleus metabolism, Cell Proliferation drug effects, Cytosol drug effects, Cytosol metabolism, DNA metabolism, Electrophoretic Mobility Shift Assay, I-kappa B Kinase antagonists & inhibitors, Male, Mice, Mice, Inbred C57BL, Nifedipine pharmacology, RNA biosynthesis, RNA genetics, Reverse Transcriptase Polymerase Chain Reaction, Blood Vessels pathology, Chemokine CCL2 biosynthesis, Inflammation pathology, NF-kappa B antagonists & inhibitors
- Abstract
Background: The effect of a calcium channel blocker (CCB) on the expression of monocyte chemoattractant protein (MCP)-1 was explored in inflammatory vascular injury, focusing on the role of nuclear factor (NF)-kappaB., Methods: Vascular injury was induced by cuff placement. Expression of MCP-1 was determined by real-time RT-PCR. NF-kappaB expression and its activity were detected by Western blot and electrophoretic mobility shift assay., Results: Polyethylene cuff placement around the mouse femoral artery increased MCP-1 expression, together with proliferation of vascular smooth muscle cells and neointimal formation in the injured artery. The content of NF-kappaB was decreased in the cytosolic fraction but increased in the nuclear fraction prepared from the injured artery. In the nuclear fraction, the binding activity of NF-kappaB to the promoter region of MCP-1 was markedly increased. On the other hand, IkappaB content in the cytosolic fraction was decreased in the injured artery after cuff placement, accompanied by an increase in IkappaB kinase (IKK) phosphorylation. Treatment of mice with a CCB, nifedipine, at a dose of 5 mg/kg/day, significantly decreased vascular smooth muscle cell proliferation and neointimal formation without affecting blood pressure. This dose of nifedipine inhibited the increase in MCP-1 expression in the injured artery. Moreover, nifedipine reduced the nuclear content and DNA-binding activity of NF-kappaB in the injured artery. In contrast, the decrease in IkappaB content and the increase in IKK phosphorylation in the cytosolic fraction were attenuated by nifedipine., Conclusions: These results indicate that MCP-1 expression in inflammatory vascular injury is regulated by activation of NF-kappaB. The results also suggest that nifedipine attenuates MCP-1 expression in the injured artery via inhibition of the nuclear translocation and DNA-binding activity of NF-kappaB, and thereby improves vascular remodeling.
- Published
- 2007
- Full Text
- View/download PDF
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