Aiko Sakamoto

University Hospital Medical Information Network, Edo, Tōkyō, Japan

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Publications (19)46.26 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Immunoglobulin G4 (IgG4)-related disease has been suggested to be involved in cardiovascular disorders such as chronic periaortitis. However, it remains unclear whether IgG4-related immuno-inflammation affects the subclinical stages of aortic remodeling. Here, we analyzed the relationship between serum IgG4 concentrations and the morphology of the ascending aorta.
    Journal of cardiology. 07/2014;
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    ABSTRACT: Objectives Immunoglobulin G4 (IgG4)-related immuno-inflammation may play a role in the development of coronary artery disease (CAD). We analyzed the association of serum IgG4 and soluble interleukin-2 receptor (sIL-2R) levels with epicardial fat volume (EFV) and coronary artery calcification (CAC). Methods Serum IgG4 and sIL-2R levels were measured in 267 patients who underwent 320-slice cardiac computed tomography. Results The median serum levels of IgG4 and sIL-2R were higher in patients with CAD than in those without. Serum IgG4 levels were significantly greater in patients with EFV within the second and fourth quartile (≥ 75 mL) than in those with low EFV (< 75 mL) (33.5 mg/dL vs. 22.5 mg/dL). On the other hand, serum sIL-2R levels were significantly higher in patients with CAC than in those without (409 U/mL vs. 345 U/mL). In age- and gender-adjusted logistic regression analysis, the fourth quartile of IgG4 (≥ 56.7 mg/dL) was associated with EFV within the second and fourth quartile (≥ 75 mL) with an odds ratio of 3.13. Conclusion Serum IgG4 levels were greater in patients with EFV within the second and fourth quartile, whereas serum sIL-2R levels were increased in patients with CAC. These two biomarkers may reflect different mechanisms underlying development of cardiovascular remodeling.
    Clinica chimica acta; international journal of clinical chemistry 01/2014; 428:63–69. · 2.54 Impact Factor
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    ABSTRACT: Background Immunoglobulin G4 (IgG4)-related disease has been suggested to be involved in cardiovascular disorders such as chronic periaortitis. However, it remains unclear whether IgG4-related immuno-inflammation affects the subclinical stages of aortic remodeling. Here, we analyzed the relationship between serum IgG4 concentrations and the morphology of the ascending aorta. Methods Serum concentrations of IgG4 were measured in 322 patients who underwent 320-slice cardiac computed tomography (CT). We assessed the aortic wall area and intravascular area at the portion between the aortic valve and the bifurcation of the pulmonary artery. Results In total, 174 patients (54.0%) were diagnosed to have coronary artery disease (CAD) by cardiac CT. The intravascular area was significantly larger in patients with CAD than in those without (893 mm2 vs. 811 mm2, p = 0.001). The aortic wall area was slightly, but not significantly, larger in patients with CAD than in those without (183 mm2 vs. 176 mm2, p = 0.051). Serum concentrations of IgG4 were significantly higher in patients with an aortic wall area of median or greater size (≥181 mm2) than in those with a smaller area (<181 mm2) (32.9 mg/dL vs. 23.1 mg/dL, p = 0.026). In logistic regression analysis using age, gender, and CAD as covariates, the fourth quartile of IgG4 (≥55.4 mg/dL) was significantly associated with an aortic wall area of median or greater size with an odds ratio of 2.09. Conclusions Serum concentrations of IgG4 were found to be significantly associated with the aortic wall area. These findings collectively suggest that immuno-inflammatory processes may play a role in the subclinical stages of aortic remodeling.
    Journal of Cardiology. 01/2014;
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    ABSTRACT: BACKGROUND: Although gastrointestinal (GI) complications are receiving more attention in cardiovascular patients owing to the widespread use of antithrombotic drugs, information seems to be limited over the prevalence of GI malignancies in those patients. METHODS AND RESULTS: The prevalence of malignant as well as non-malignant GI lesions diagnosed in cardiology inpatients was investigated. We retrospectively analyzed 274 cardiology inpatients who underwent upper and/or lower GI tract endoscopies. A total of 97 patients (35.4%) were taking multiple antithrombotic drugs and the mean number of antithrombotic drugs used was 1.19. Malignant neoplasm was found in 26 patients (9.5%), and non-malignant lesions (ulcers, adenomas, polyps) were found in 106 patients (38.7%). Multivariate analysis showed that antiplatelet drug usage was negatively (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.16-0.91) whereas positive fecal occult blood test was positively (OR 4.44, 95% CI 1.44-13.66) associated with GI malignancies. On the other hand, for non-malignant GI lesions, both antiplatelet drug usage (OR 1.85, 95% CI 1.05-3.25) and positive fecal occult blood test (OR 1.99, 95% CI 1.14-3.47) were found to be positive predictors. CONCLUSIONS: During the 59-month study period, 26 and 106 patients were diagnosed to have GI malignancies and non-malignant GI lesions, respectively, among cardiology inpatients. Cardiology physicians should not overlook the possibility of GI malignancies in an era of multiple antithrombotic drug usage.
    Journal of Cardiology 11/2012; · 2.30 Impact Factor
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    ABSTRACT: Aim: Serum gamma-glutamyltransferase (GGT) levels, which are associated with insulin resistance, may predict the incidence of cardiovascular disease and mortality. Here, the relationship was analyzed between changes in obesity parameters and those in serum GGT over a one-year period.Methods: Data were analyzed from individuals who underwent general health screening two years running.Results: Among 3086 individuals (1954 men, 1132 women), percent changes in both waist circumference (%dWC) and body mass index (BMI) (%dBMI) were significantly correlated with percent changes in GGT (%dGGT) in men (r=0.17 and r=0.31, respectively). On the other hand, in women, %dBMI, but not %dWC, had a significant association with %dGGT. When age, %dWC, %dBMI, smoking status, and alcohol intake were all included as independent variables, %dBMI, but not %dWC, showed a graded association with the highest %dGGT quartile in both genders. Furthermore, incorporation of %dWC as an additional independent variable to age, gender, and %dBMI did not show an incremental improvement in prediction for the highest %dGGT quartile (C statistic, 0.643 to 0.648; p= 0.380), suggesting that taking WC changes into account does not significantly improve the prediction of GGT changes when BMI has already been taken into consideration.Conclusion: Changes in BMI are dose-dependently associated with GGT changes in both genders; however, the additional consideration of changes in WC does not show a significant statistical improvement in the prediction of GGT changes.
    Journal of atherosclerosis and thrombosis 09/2012; · 2.93 Impact Factor
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    ABSTRACT: An excess of lipids may accumulate in the kidney in conditions such as diabetes and hypertension, and can potentially cause renal injury. We previously reported that an infusion of angiotensin II into a rat induced deposition of lipids in the renal tubular epithelial cells. Here we have examined the effect of pioglitazone, an agonist of the peroxisome proliferator-activated receptor-γ (PPAR-γ), on renal lipid accumulation and renal injury induced by angiotensin II infusion. Pioglitazone treatment (2.5mg/kg/day) reduced the amount of triglycerides in the kidney of the angiotensin II-induced hypertensive rat without significantly altering either blood pressure levels or mRNA expression of lipogenic genes in the kidney. In addition, pioglitazone, either alone or in conjunction with angiotensin II, increased the expression of phosphorylated, but not total, AMP-activated protein kinase (AMPK). Proteinuria and kidney weight in the angiotensin II-infused rat were significantly decreased by pioglitazone treatment. In addition, pioglitazone suppressed iron deposition and ferritin protein induction, but did not alter upregulated expression of the antioxidative molecule, heme oxygenase-1, in the kidney of the angiotensin II-infused rat. These findings suggested that pioglitazone suppressed the angiotensin II-induced increase in renal lipid content by inhibiting its proteinuric action, but not by direct alteration of the expression or activity of lipid metabolism-related genes. Reduction of lipotoxic renal damage may represent one of the renoprotective effects provided by pioglitazone in hypertension with activation of the renin-angiotensin system.
    European journal of pharmacology 02/2012; 682(1-3):131-6. · 2.59 Impact Factor
  • Atherosclerosis 02/2012; 221(2):602-3. · 3.71 Impact Factor
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    ABSTRACT: We previously showed that administration of angiotensin II to rats causes fibrosis and lipid accumulation in the heart. In the current study, we examined the effect of pioglitazone, an agonist of peroxisome proliferator activated receptor-γ, on angiotensin II-induced intracardiac lipid accumulation and cardiac dysfunction. Pioglitazone, given orally at a dose of 2.5mg/kg/d, reduced cardiac triglyceride content and suppressed lipid deposition in the heart of angiotensin II-induced hypertensive rats without affecting angiotensin II-induced upregulation of lipogenic gene expression. Histological examination showed that pioglitazone reduced the area of cardiac fibrosis and iron deposition in the heart of angiotensin II-treated rats. Expression of an antioxidative molecule, heme oxygenase-1, was increased by angiotensin II infusion, and pioglitazone treatment preserved expression of HO-1. Angiotensin II increased the superoxide signals detected by dihydroethidium staining in myocardial cells with lipid deposition, and this increase was suppressed by pioglitazone. Cardiac function was analyzed in an ex vivo isolated cardiac perfusion system. It was found that pioglitazone improved both the systolic and diastolic cardiac performance, which was weakened by angiotensin II infusion, after transient ischemia and reperfusion. These findings collectively suggest that pioglitazone treatment ameliorated the histological and functional cardiac damage induced by angiotensin II infusion, the mechanism of which may be related to the antioxidative action of pioglitazone.
    International journal of cardiology 01/2012; · 7.08 Impact Factor
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    ABSTRACT: Retroperitoneal fibrosis, inflammatory aortic aneurysm, and pericardial and mediastinal fibrosis are characterized by infiltration of immuno-inflammatory cells and deposition of thickened fibrous tissues. Several recent studies suggested that an immunoglobulin-G4 (IgG4)-related immunological mechanism may play a role in these diseases. By searching the clinical database of patients admitted to our department between 2000 and 2010, we summarized the clinical data of 11 patients who were diagnosed to have these disorders. The diagnoses were idiopathic retroperitoneal fibrosis (8 cases), mediastinal and/or pericardial fibrosis (4 cases), inflammatory abdominal aneurysm (2 cases), and inflammatory coronary periarteritis (1 case). Hypertension, diabetes, and dyslipidemia were found in 45%, 36%, and 55%, respectively, in these patients, and they were all either current or former smokers. Two patients with pericardial involvement showed a rushed clinical course, resulting in in-hospital death. Serum levels of IgG were elevated in 67%, and soluble interleukin-2 receptor was elevated in 75%, when measured. Immunohistochemical analysis showed marked infiltration of IgG4-positive plasma cells in the pericardium in patients who died of constrictive pericarditis. Our data support the notion that immune-inflammatory mechanism, which might be IgG4-related sometimes, may play a role in idiopathic retroperitoneal fibrosis, inflammatory aortic aneurysm, and mediastinal/pericardial fibrosis, although clinical course may differ substantially.
    Journal of Cardiology 12/2011; 59(2):139-46. · 2.30 Impact Factor
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    ABSTRACT: The cardiovascular system may be involved as a target organ of multifocal fibrosclerosis, which may manifest as idiopathic retroperitoneal fibrosis, inflammatory aortic aneurysm, inflammatory periarteritis, and inflammatory pericarditis. These pathological conditions can sometimes occur concomitantly. Idiopathic retroperitoneal fibrosis and inflammatory abdominal aortic aneurysm are both characterized by the presence of fibro-inflammatory tissue around the abdominal aorta expanding into the surrounding retroperitoneal structures, and together they may be termed 'chronic periaortitis'. Cardiovascular fibrosclerosis has become non-uncommonly encountered condition since imaging modalities have made its diagnosis more feasible. In addition, recent studies have demonstrated that a certain fraction, but not all, of cardiovascular fibrosclerosis may have a link with immunoglobulin-G4 (IgG4)-related sclerosing disease (IgG4-SD). IgG4-SD is histologically characterized by dense fibrosclerosis and infiltration of lymphocytes and IgG4-positive plasma cells, and these histopathologic findings seem to be essentially similar regardless of the organs involved. In this mini review, we summarize what is known so far about multifocal fibrosclerosis of the cardiovascular system and its association with IgG4-SD, and what remains to be clarified in future investigations.
    Journal of Cardiology 12/2011; 59(2):132-8. · 2.30 Impact Factor
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    ABSTRACT: Immunoglobulin G4 (IgG4)-related immuno-inflammation has been suggested to play a role in the development of remodeling of arterial wall. We investigated the association between serum concentrations of IgG4 or soluble interleukin-2 receptor (sIL-2R) and coronary artery disease (CAD). Serum concentrations of IgG4 and sIL-2R were measured in 286 patients who underwent coronary angiography. In patients with CAD, the medians of serum concentrations of IgG4 (39.3 mg/dl) and sIL-2R (388 U/ml) were significantly higher than corresponding values in patients without CAD (IgG4 27.0 mg/dl, sIL-2R 312 U/ml). In receiver-operating characteristic curve analysis, the area under the curve of sIL-2R and IgG4 for the presence of CAD was 0.634 and 0.632, respectively. Age- and gender-adjusted logistic regression analysis showed that both of the fourth quartile of sIL-2R concentrations (≥509 U/ml) and that of IgG4 concentrations (≥57.7 mg/dl) were found to be associated with CAD with an odds ratio of 2.82 and 4.08, respectively, compared with the corresponding lowest quartile. Serum concentrations of IgG4 and sIL-2R were increased in patients with angiographically-proven CAD, suggesting that IgG4-related immuno-inflammation may also have a role in the development and/or progression of coronary artery atherosclerosis.
    Clinica chimica acta; international journal of clinical chemistry 11/2011; 413(5-6):577-81. · 2.54 Impact Factor
  • Nobukazu Ishizaka, Aiko Sakamoto
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 10/2011; 54(4):1233; author reply 1233-4. · 3.52 Impact Factor
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    ABSTRACT: Nowadays, antiplatelet and anticoagulant drug medications are indicated in patients with a variety of cardiovascular disorders, such as atrial fibrillation, coronary artery disease, and peripheral artery disease. Among cardiology patients, regardless of gastrointestinal (GI) protection, we do not infrequently encounter those patients who have signs and symptoms that are suggestive of GI tract problems. We should bear in mind that such GI signs and symptoms may be attributed to GI cancers, as well as to benign or clinically insignificant lesions. Several clinical studies have shown, albeit controversially that the predictive value of positive fecal occult blood for colorectal malignant neoplasm may not be lower in patients taking antithrombotic medication. In addition, it has been shown that in patients taking antithrombotic drug(s), diagnosed colorectal malignancies are in a relatively earlier phase, suggesting that antithrombotic drugs may facilitate the detection of otherwise unrecognized cancers. The possibility also exists that certain cardiovascular disease may be associated with a higher risk of GI malignant neoplasms. There has been no established evidence concerning whether more aggressive GI tract screening will reduce the probability of cancer death in cardiology patients; nevertheless, GI tract lesions should not be overlooked among cardiology patients, especially when unexplained anemia, gastrointestinal symptoms, or positive fecal occult blood test is present, and GI tract screening should be performed with appropriate timing.
    Journal of Cardiology 09/2011; 58(3):199-207. · 2.30 Impact Factor
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    ABSTRACT: Activation of the renin-angiotensin system may be involved in the development of hepatic steatosis, a condition that is associated with insulin resistance. We showed that in rats, angiotensin II induced accumulation of triglycerides in the renal tubular and cardiac cells, although it significantly reduced the weight of the rats. Here we investigated the liver lipid content of rats given long-term angiotensin II administration. Angiotensin II (0.7 mg/kg/day) was infused into the rats for 7 days via an osmotic minipump. Some rats also received hydralazine or losartan concomitantly. It was shown that angiotensin II reduced oil red O-stainable lipid droplets (6% of the control value) and liver triglyceride content (angiotensin II: 4.6 ± 0.8 µg/mg, control: 11.7 ± 1.1 µg/mg). Both of these phenomena were blocked by losartan, but not by hydralazine. Angiotensin II infusion reduced the expression and activity of AMP-activated protein kinase. In addition, angiotensin II decreased the mRNA expression of peroxisome proliferator-activated receptor-α and genes related to β-oxidation, although mRNA expression of genes related to lipogenesis were not affected. Angiotensin II reduced triglyceride content in the liver, unlike in the kidney or heart, via an AT1 receptor-dependent mechanism.
    Journal of Renin-Angiotensin-Aldosterone System 08/2011; 12(4):462-8. · 2.29 Impact Factor
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    ABSTRACT: Changes in indexes of obesity, such as waist circumference (WC) and body mass index (BMI), may influence some glucose metabolism-related parameters in both obese and non-obese subjects. We have investigated the impact of changes in WC and in BMI on data related to glucose metabolism over a one-year period. Data from 3213 individuals (2014 men, 1199 women) who underwent a general health screening two years running and were not taking antidiabetic medication were analyzed. In men, percent changes in WC (%dWC) and BMI (%dBMI) were both significantly correlated with percent changes in fasting glucose (%dFG), in hemoglobin A(1C) (%dHbA(1C)), and in HOMA-IR (%dHOMA-IR). In women, these relationships were not significant except for the relationship between %dBMI and %dHOMA-IR. In a multivariate linear regression analysis using age, %dBMI, and %dWC as independent variables, %dBMI, but not %dWC, was found to be an independent predictor of %dHOMA-IR in both genders. Furthermore, in men, %dBMI was also an independent factor predicting %dFG and %dHbA(1C). During the one-year period, a reduction in BMI, and thus weight loss, was found to be associated with the improvement of insulin sensitivity, especially in men. A reduction in WC was also associated with an improvement in insulin sensitivity in men; however, this relationship did not remain significant after controlling for changes in BMI.
    Journal of atherosclerosis and thrombosis 09/2010; 17(12):1246-55. · 2.93 Impact Factor
  • Journal of atherosclerosis and thrombosis 03/2010; 17(8):889-90. · 2.93 Impact Factor
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    ABSTRACT: Unfavorable lipid accumulation may occur in the kidneys in the presence of metabolic syndrome and diabetes. The aim of this study was to investigate whether excess lipids would accumulate in the kidneys of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of metabolic syndrome. From 34 weeks of age, OLETF rats were treated orally with a calcium channel blocker, benidipine (3 mg kg(-1) per day), or an AT1 receptor blocker, losartan (25 mg kg(-1) per day), for 8 weeks. Blood pressure was slightly but significantly higher in the untreated OLETF rats (149+/-4 mm Hg) than in Long-Evans Tokushima Otsuka (LETO) rats (136+/-2 mm Hg), and both losartan (135+/-3 mm Hg) and benidipine (138+/-3 mm Hg) reduced blood pressure in OLETF rats to a level comparable to that in LETO rats. Tissue content of triglycerides (TG) was greater in OLETF rats than in LETO rats (6.24+/-3.77 and 2.85+/-1.32 microg mg(-1) x tissue, respectively), and both losartan and benidipine reduced these values. Histological analysis showed lipid droplets in tubular cells in which increased dihydroethidium fluorescence was present. Expression of peroxisome proliferator-activated receptor-alpha, PGC-1alpha and uncoupling protein-2 was found to be higher in OLETF rats than in LETO rats; however, the expression of these genes was not altered by treatment with either antihypertensive drug. In contrast, both losartan and benidipine increased the amount of total and phosphorylated forms of AMP kinase and the expression of carnitine palmitoyltransferase-1 (CPT-1). In conclusion, treatment of OLETF rats with losartan and benidipine reduced the tissue content of TG, decreased the production of superoxide and regulated the expression of genes related to fatty acid oxidation such as AMP-activated protein kinase and CPT-1 in the kidneys.
    Hypertension Research 03/2010; 33(3):263-8. · 2.79 Impact Factor
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    ABSTRACT: A 65-year-old male, who had been diagnosed to have myasthenia gravis (MG) 25 years previously, was admitted to our hospital with faintness. Cardiac ultrasonography showed decreased left ventricular function. Magnetic resonance imaging depicted delayed contrast enhancement in localized regions. No significant coronary artery stenosis was found, and due to the reproducible susceptibility for sustained ventricular tachycardia, he underwent cardioverter-defibrillator implantation. Although relatively uncommon, cardiac manifestations should not be overlooked in MG patients, as they may be associated with ventricular arrhythmias and cardiac dysfunction.
    Journal of Cardiology Cases 01/2010; 2(1).
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    ABSTRACT: A patient with recurrent abdominal pain was admitted to our hospital. Computed tomography showed a soft dense mass surrounding the abdominal aorta at the infrarenal level, which was compatible with retroperitoneal fibrosis. (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography showed abnormal uptake of (18)F-FDG into these lesions. Two months after the initiation of corticosteroid therapy, the abnormal uptake of (18)F-FDG had ceased along with a reduction in the fibrous mass surrounding the abdominal aorta.
    International Heart Journal 08/2006; 47(4):645-50. · 1.23 Impact Factor