Publications (13)56.02 Total impact
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Article: Stent-anchored coil embolotherapy - novel treatment procedure for huge pulmonary arterio-venous malformation in hereditary hemorrhagic telangiectasia.
International journal of cardiology 03/2012; 157(1):122-4. · 7.08 Impact Factor -
Article: Longest survivor of pulmonary atresia with ventricular septal defect: well-developed major aortopulmonary collateral arteries demonstrated by multidetector computed tomography.
Circulation 11/2011; 124(19):2155-7. · 14.74 Impact Factor -
Article: Serum levels of advanced glycation end products (AGEs) are inversely associated with the number and migratory activity of circulating endothelial progenitor cells in apparently healthy subjects.
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ABSTRACT: Endothelial progenitor cells (EPCs) have been shown to participate in the process of vascular repair, thus playing a protective role against cardiovascular disease (CVD). It is known that atherosclerotic risk factors could affect EPC number and function. Advanced glycation end products (AGEs) contribute to the pathogenesis of atherosclerosis as well. However, as far as we know, there is no report to show the relationship between serum AGE levels and circulating EPCs in humans. Therefore, in this study, we investigated whether serum level of AGEs was associated with EPC number and functions in apparently healthy subjects, independent of traditional cardiovascular risk factors. Apparently healthy volunteers (34.6 ± 6.9 years old, 40 males and 8 females) who were not on any medications underwent a complete history and physical examination, determination of blood chemistries, including AGEs, and number, differentiation and migratory activity of circulating EPCs. Serum AGEs levels were 9.20 ± 1.85 U/mL. Multiple stepwise regression analysis revealed that serum levels of AGEs and smoking were independently correlated with reduced number of EPCs. Further, female, AGEs, and reduced HDL-cholesterol levels were independently associated with impaired migratory activity of circulating EPCs. This study demonstrated for the first time that the serum level of AGEs was one of the independent correlates of decreased cell number and impaired migratory activity of circulating EPCs in apparently healthy subjects. Our present observations suggest that even in young healthy subjects, serum level of AGEs may be a biomarker that could predict the progression of atherosclerosis and future cardiovascular events.Cardiovascular Therapeutics 02/2011; 30(4):249-54. · 2.35 Impact Factor -
Article: Ezetimibe, an inhibitor of intestinal cholesterol absorption, decreases serum level of malondialdehyde-modified low-density lipoprotein in patients with hypercholesterolemia.
International journal of cardiology 02/2011; 146(3):420-1. · 7.08 Impact Factor -
Article: Administration of pigment epithelium-derived factor inhibits left ventricular remodeling and improves cardiac function in rats with acute myocardial infarction.
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ABSTRACT: Oxidative stress and inflammation are involved in cardiac remodeling after acute myocardial infarction (AMI). We have found that pigment epithelium-derived factor (PEDF) inhibits vascular inflammation through its anti-oxidative properties. However, effects of PEDF on cardiac remodeling after AMI remain unknown. We investigated whether PEDF could inhibit left ventricular remodeling and improve cardiac function in rats with AMI. AMI was induced in 8-week-old Sprague-Dawley rats by ligation of the left ascending coronary artery. Rats were treated intravenously with vehicle or 10 μg PEDF/100 g b.wt. every day for up to 2 weeks after AMI. Each rat was followed until 16 weeks of age. PEDF levels in infarcted areas and serum were significantly decreased at 1 week after AMI and remained low during the observational periods. PEDF administration inhibited apoptotic cell death and oxidative stress generation around the infarcted areas at 2 and 8 weeks after AMI. Further, PEDF injection suppressed cardiac fibrosis by reducing transforming growth factor-β and type III collagen expression, improved left ventricular ejection fraction, ameliorated diastolic dysfunction, and inhibited the increase in left ventricular mass index at 8 weeks after AMI. The present study demonstrated that PEDF could inhibit tissue remodeling and improve cardiac function in AMI rats. Substitution of PEDF may be a novel therapeutic strategy for cardiac remodeling after AMI.American Journal Of Pathology 02/2011; 178(2):591-8. · 4.89 Impact Factor -
Article: The p66shc gene expression in peripheral blood monocytes is increased in patients with coronary artery disease.
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ABSTRACT: The p66(shc) protein has been shown to control cellular responses to oxidative stress, being involved in atherosclerosis in animal models. However, the relationship between the p66(shc) gene expression levels and coronary artery disease (CAD) in humans remains unknown. In this study, we examined whether the p66(shc) gene expression in peripheral blood monocytes (PBMs) was increased in patients with CAD, compared with age- and sex-matched subjects without CAD. We hypothesize that the p66(shc) gene expression level in PBMs is increased in patients with CAD. Forty consecutive Japanese subjects who underwent coronary angiography for suspected CAD were enrolled in this study. The p66(shc) gene expression levels in PBMs were quantitatively measured by real-time reverse transcription-polymerase chain reactions. Uni- and multivariate analyses were applied for the correlates of CAD. CAD was diagnosed if there was > 75% obstruction of at least 1 major coronary artery or a history of percutaneous coronary intervention. There were no significant differences of blood chemistries and clinical characteristics between the patients with and without CAD, except the number of subjects who were on hypertension medication. The p66(shc) gene expression levels in PBMs were significantly higher in CAD patients compared with non-CAD subjects. Multiple stepwise regression analysis revealed that the p66(shc) gene expression levels and hypertension medication were independently related to CAD (R(2)=0.287). Further, the p66(shc) gene expres- sion levels were significantly increased (P < 0.05) in proportion to the number of diseased vessels. The present study is the first demonstration that increased the p66(shc) gene expression in PBMs is independently associated with CAD in Japanese subjects. The p66(shc) gene expression level in PBMs may be a novel biomarker of CAD in humans.Clinical Cardiology 09/2010; 33(9):548-52. · 2.15 Impact Factor -
Article: An alpha-glucosidase inhibitor, acarbose treatment decreases serum levels of glyceraldehyde-derived advanced glycation end products (AGEs) in patients with type 2 diabetes.
Clinical and Experimental Medicine 10/2009; 10(2):139-41. · 1.58 Impact Factor -
Article: Factors associated with serum high mobility group box 1 (HMGB1) levels in a general population.
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ABSTRACT: High mobility group box 1 (HMGB1), a nonhistone chromatin-associated protein, is implicated as a mediator of both infectious and non-infectious inflammatory conditions. Clinical research on this protein in humans just has begun; serum HMGB1 was reported to be elevated in a small number of critically ill patients suffering from sepsis. However, the kinetics, distribution and factors associated with circulating HMGB1 are unknown in a general population. In this study, we examined these issues in a large population of healthy subjects. Fasting blood samples were obtained from 626 subjects (237 males and 389 females). HMGB1 levels showed a skewed distribution with a mean of 1.65 +/- 0.04 ng/ml. Multiple stepwise regression analyses found that white blood cell (WBC) counts (P = .016) and the soluble form of receptor for advanced glycation end products (sRAGE; P < .001, inversely), which is also known to be a receptor for HMGB1, were independently associated with HMGB1 levels. We demonstrated for the first time that circulating HMGB1 levels were inversely associated with sRAGE levels in a general population. Because RAGE is involved in HMGB1 signaling, our present study suggests that sRAGE may capture and eliminate circulating HMGB1 in humans.Metabolism: clinical and experimental 08/2009; 58(12):1688-93. · 2.59 Impact Factor -
Article: Low-density lipoprotein levels are one of the independent determinants of circulating levels of advanced glycation end products in nondiabetic subjects.
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ABSTRACT: Nonenzymatic modification of proteins by reducing sugars leads to the formation of advanced glycation end products (AGEs), whose process has been reported to progress under diabetes. Recently, diet has been found to be a major environmental source of proinflammatory AGEs in humans. Further, fats or meat-derived products processed by high heat such as broiling have been shown to contain more AGEs than carbohydrates boiled for longer periods. Since circulating levels of low-density lipoprotein cholesterol (LDL-C) are also regulated by dietary cholesterol, it is conceivable that intake of cholesterol-rich foods could regulate serum levels of AGEs in humans. In this study, we investigated whether LDL-C levels are one of the independent determinants of circulating AGEs levels in a nondiabetic general population. A total of 170 nondiabetic Japanese subjects underwent a complete history, physical examination, determination of blood chemistries, and serum AGEs. Univariate analysis showed that AGEs levels were associated with LDL-C (P < 0.05) and fasting plasma glucose levels (P < 0.05). By the use of multiple stepwise regression analyses, LDL-C (P < 0.01) and fasting plasma glucose levels (P < 0.05) remained significant and were independently related to AGEs levels (R2 = 0.069). The present study is the first demonstration that LDL-C levels are one of the independent determinants of serum levels of AGEs in a nondiabetic general population. Intake of cholesterol-rich foods may regulate serum levels of AGEs in nondiabetic subjects.Clinical Cardiology 07/2009; 32(9):E12-5. · 2.15 Impact Factor -
Article: Pigment epithelium-derived factor (PEDF) administration inhibits occlusive thrombus formation in rats: a possible participation of reduced intraplatelet PEDF in thrombosis of acute coronary syndromes.
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ABSTRACT: Although remarkable therapeutic advances in the treatment of acute coronary syndromes (ACS) have been made with anti-platelet therapy, the therapeutic options may be limited by considerable side effects. Pigment epithelium-derived factor (PEDF) has anti-oxidative properties and may play a protective role against atherosclerosis. In this study, we investigated whether PEDF prevented occlusive thrombus formation in rats. Occlusive thrombus formation was induced by treating rats with ligation and cuff placement at the left common carotid artery. Intravenous injection of PEDF dose-dependently inhibited thrombus formation and blocked the increase in immunoreactivity of P-selectin, a marker of platelet activation, NADPH oxidase activity and superoxide generation in thrombi. In vitro, PEDF significantly decreased collagen-induced reactive oxygen species generation in platelets and subsequently suppressed the platelet activation and aggregation. Plasma and intraplatelet levels of PEDF in the coronary circulation in patients with ACS were significantly lower than those in age- and gender-matched controls without coronary artery disease. These results demonstrated that PEDF administration could inhibit occlusive thrombus formation by blocking the platelet activation and aggregation through its anti-oxidative properties. Our present study suggests that pharmacological up-regulation or substitution of PEDF may offer a promising strategy for the treatment of arterial thrombosis.Atherosclerosis 04/2008; 197(1):25-33. · 3.79 Impact Factor -
Article: Administration of pigment epithelium-derived factor (PEDF) inhibits cold injury-induced brain edema in mice.
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ABSTRACT: Brain edema is the most life-threatening complication that occurs as a result of a number of insults to the brain. However, its therapeutic options are insufficiently effective. We have recently found that administration of pigment epithelium-derived factor (PEDF) inhibits retinal hyperpermeability in rats by counteracting biological effects of vascular endothelial growth factor (VEGF). In this study, we investigated whether PEDF could inhibit cold injury-induced brain edema in mice. Cold injury was induced by applying a pre-cooled metal probe on the parietal skull. VEGF and its receptor Flk-1 gene and/or protein expressions were up-regulated in the cold-injured brain. Cold injury induced brain edema, which was reduced by intraperitoneal injection of VEGF antibodies (Abs) or apocynin, an inhibitor of NADPH oxidase. PEDF mRNA and protein levels were up-regulated in response to cold injury. PEDF dose-dependently inhibited the brain edema, whose effect was neutralized by simultaneous treatments with anti-PEDF Abs. Although VEGF and Flk-1 gene and/or protein expressions were not suppressed by PEDF, PEDF or anti-VEGF Abs inhibited the cold injury-induced NADPH oxidase activity in the brain. Further, PEDF treatment inhibited activation of Rac-1, an essential component of NADPH oxidase in the cold-injured brain, while it did not affect mRNA levels of gp91phox, p22phox, or Rac-1. These results demonstrate that PEDF could inhibit the cold injury-induced brain edema by blocking the VEGF signaling to hyperpermeability through the suppression of NADPH oxidase via inhibition of Rac-1 activation. Our present study suggests that PEDF may be a novel therapeutic agent for the treatment of brain edema.Brain Research 10/2007; 1167:92-100. · 2.73 Impact Factor -
Article: Advanced glycation end products (AGEs) and cardiovascular disease (CVD) in diabetes.
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ABSTRACT: Accelerated atherosclerosis and microvascular complications are perhaps the leading cause of coronary heart disease, blindness and renal failure, which could account for disabilities and high mortality rates in patients with diabetes. Several mechanisms including endothelial cell damage, platelet activation and aggregation, hypercoagulability, and impaired fibrinolysis are involved in the pathogenesis of thrombogenic diathesis in diabetes. However, the underlying molecular mechanism is not fully elucidated. A recent clinical study, the Diabetes Control and Complications Trial-Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC) Research, has revealed that the reduction in the risk of progressive retinopathy and nephropathy resulting from intensive therapy in patients with type 1 diabetes persist for at least several years, despite increasing hyperglycemia. In addition, intensive therapy during the DCCT also reduced the risk of cardiovascular events by about 50 % in type 1 diabetic patients 11 years after the end of the trial. These clinical studies strongly suggest that so-called 'hyperglycemic memory' causes chronic abnormalities in diabetic vessels that are not easily reversed, even by subsequent, relatively good control of blood glucose. Among various biochemical pathways implicated in diabetic vascular complications, the process of formation and accumulation of advanced glycation end products (AGEs) and their mode of action are most compatible with the theory 'hyperglycemic memory'. In this review, we discuss the role of AGEs in thrombogenic abnormalities in diabetes, especially focusing on the deleterious effects of these macroproteins on endothelial cell function, platelet activation and aggregation, coagulation and fibrinolytic systems.Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents) 08/2007; 5(3):236-40. -
Article: Pigment epithelium-derived factor inhibits neointimal hyperplasia after vascular injury by blocking NADPH oxidase-mediated reactive oxygen species generation.
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ABSTRACT: Pigment epithelium-derived factor (PEDF) inhibits cytokine-induced endothelial cell activation through its antioxidative properties. However, the effect of PEDF on restenosis remains to be elucidated. Because the pathophysiological feature of restenosis is characterized by increased superoxide formation and accumulation of smooth muscle cells (SMCs), PEDF may inhibit this process via suppression of reactive oxygen species generation. We investigated here whether PEDF could prevent neointimal formation after balloon injury. PEDF levels were decreased in balloon-injured arteries. Adenoviral vector encoding human PEDF (Ad-PEDF) prevented neointimal formation. Expression and superoxide generation of the membrane components of NADPH oxidase, p22(phox) and gp91(phox), in the neointima were also suppressed by Ad-PEDF. Ad-PEDF reduced G(1) cyclin (cyclin D1 and E) expression and increased p27, a cyclin-dependent kinase inhibitor. In vitro, PEDF inhibited platelet-derived growth factor-BB-induced SMC proliferation and migration by blocking reactive oxygen species generation through suppression of NADPH oxidase activity via down-regulation of p22(PHOX) and gp91(PHOX). PEDF down-regulated G(1) cyclins and up-regulated p27 levels in platelet-derived growth factor-BB-exposed SMCs as well. These results demonstrate that PEDF could inhibit neointimal formation via suppression of NADPH oxidase-mediated reactive oxygen species generation. Our present study suggests that substitution of PEDF may be a novel therapeutic strategy for restenosis after balloon angioplasty.American Journal Of Pathology 07/2007; 170(6):2159-70. · 4.89 Impact Factor
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2007–2012
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Kurume University
- Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications
Kurume, Fukuoka-ken, Japan
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