30 results on '"Sata, Masataka"'
Search Results
2. Atherosclerotic Coronary Plaque Is Associated With Adventitial Vasa Vasorum and Local Inflammation in Adjacent Epicardial Adipose Tissue in Fresh Cadavers.
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Ito H, Wakatsuki T, Yamaguchi K, Fukuda D, Kawabata Y, Matsuura T, Kusunose K, Ise T, Tobiume T, Yagi S, Yamada H, Soeki T, Tsuruo Y, and Sata M
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- Adipose Tissue chemistry, Adipose Tissue pathology, Adventitia chemistry, Adventitia pathology, Aged, Aged, 80 and over, Cadaver, Coronary Artery Disease metabolism, Coronary Artery Disease pathology, Coronary Vessels chemistry, Coronary Vessels pathology, Female, Humans, Inflammation metabolism, Inflammation pathology, Inflammation Mediators analysis, Male, Predictive Value of Tests, Vasa Vasorum chemistry, Vasa Vasorum pathology, Adipose Tissue diagnostic imaging, Adventitia diagnostic imaging, Coronary Artery Disease diagnostic imaging, Coronary Vessels diagnostic imaging, Inflammation diagnostic imaging, Plaque, Atherosclerotic, Ultrasonography, Interventional, Vasa Vasorum diagnostic imaging
- Abstract
Background: The coronary adventitia has recently attracted attention as a source of inflammation because it harbors nutrient blood vessels, termed the vasa vasorum (VV). This study assessed the link between local inflammation in adjacent epicardial adipose tissue (EAT) and coronary arterial atherosclerosis in fresh cadavers.Methods and Results:Lesion characteristics in the left anterior descending coronary artery of 10 fresh cadaveric hearts were evaluated using integrated backscatter intravascular ultrasound (IB-IVUS), and the density of the VV and levels of inflammatory molecules from the adjacent EAT were measured for each of the assessed lesions. The lesions were divided into lipid-rich, lipid-moderate, and lipid-poor groups according to percentage lipid volume assessed by IB-IVUS. Higher expression of inflammatory molecules (i.e., vascular endothelial growth factor A [VEGFA] andVEGFB) was observed in adjacent EAT of lipid-rich (n=11) than in lipid-poor (n=11) lesions (7.99±3.37 vs. 0.45±0.85 arbitrary units [AU], respectively, forVEGFA; 0.27±0.15 vs. 0.11±0.07 AU, respectively, forVEGFB; P<0.05). The density of adventitial VV was greater in lipid-rich than lipid-poor lesions (1.50±0.58% vs. 0.88±0.23%; P<0.05)., Conclusions: Lipid-rich coronary plaques are associated with adventitial VV and local inflammation in adjacent EAT in fresh cadavers. This study suggests that local inflammation of EAT is associated with coronary plaque progression via the VV.
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- 2020
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3. Association of Local Epicardial Adipose Tissue Depots and Left Ventricular Diastolic Performance in Patients With Preserved Left Ventricular Ejection Fraction.
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Maimaituxun G, Yamada H, Fukuda D, Yagi S, Kusunose K, Hirata Y, Nishio S, Soeki T, Masuzaki H, Sata M, and Shimabukuro M
- Subjects
- Adipose Tissue diagnostic imaging, Aged, Aged, 80 and over, Computed Tomography Angiography, Coronary Angiography, Cross-Sectional Studies, Diastole, Echocardiography, Doppler, Pulsed, Female, Humans, Male, Middle Aged, Multidetector Computed Tomography, Pericardium diagnostic imaging, Retrospective Studies, Risk Factors, Ventricular Dysfunction, Left diagnostic imaging, Ventricular Dysfunction, Left physiopathology, Adipose Tissue physiopathology, Adiposity, Pericardium physiopathology, Stroke Volume, Ventricular Dysfunction, Left etiology, Ventricular Function, Left
- Abstract
Background: Although full-volume quantification of epicardial adipose tissue (EAT) is a predictor of LV diastolic dysfunction (LVDD), how localized EAT depots are linked to LVDD remains unclear. We evaluated the effect of local EAT depots on LV diastolic function parameters in patients with preserved LV ejection fraction (LVEF).Methods and Results:From 423 consecutive patients who underwent cardiac CT angiography, we recruited 252 with sinus rhythm and normal LVEF. The EAT volume index (EATV/body surface area) and the localized EAT thickness around the right coronary artery (EAT
RCA ), left anterior descending artery (EATLAD ), left circumflex artery (EATLCX ), right ventricle (EATRV ), left ventricle (EATLV ), right atrium (EATRA ), and left atrium (EATLA ) were measured using cardiac CT. In the LVDD group (n=71), the EATV index (75±30 vs. 64±28 mL/m2 , P=0.010), EATLCX (10.7±3.8 vs. 9.4±3.4 mm, P=0.008), and EATLV (2.6±1.6 vs. 2.1±1.4 mm, P=0.024) were greater than in the non-LVDD group (n=181). In contrast, EATLCX and EATLV were markedly associated with decreased lateral e' and increased lateral E/e'. Multiple regression analysis indicated that EATLCX and EATLV were strongly associated with LV diastolic function parameters., Conclusions: Localized EAT depots are linked to altered mitral annular motion. Further study is warranted to clarify whether localized EAT depots are functionally linked to the clinical manifestations of LVDD.- Published
- 2020
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4. Usefulness of Epicardial Adipose Tissue Volume to Predict Recurrent Atrial Fibrillation After Radiofrequency Catheter Ablation.
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Maeda M, Oba K, Yamaguchi S, Arasaki O, Sata M, Masuzaki H, and Shimabukuro M
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- Aged, Atrial Fibrillation surgery, Echocardiography methods, Female, Follow-Up Studies, Heart Atria diagnostic imaging, Heart Ventricles diagnostic imaging, Heart Ventricles physiopathology, Humans, Male, Middle Aged, Postoperative Period, Predictive Value of Tests, Prognosis, ROC Curve, Recurrence, Retrospective Studies, Risk Factors, Ventricular Function, Left physiology, Adipose Tissue diagnostic imaging, Atrial Fibrillation diagnosis, Catheter Ablation methods, Multidetector Computed Tomography methods, Pericardium diagnostic imaging
- Abstract
Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with post-ablation atrial fibrillation (AF), ranges of EATV predictive of post-ablation recurrence of AF remain unclear. In this study, we evaluated: (1) relationships between EATV and characteristics of AF, (2) impact of EATV on recurrent AF after radiofrequency ablation; , and (3) cut-off point for recurrent AF using a receiver operating characteristic curve. In 218 consecutive symptomatic patients undergoing who underwent ablation for AF (143 paroxysmal AF; 78 persistent AF), the EATV index (EATVI: EATV/body surface area, mL/m
2 ) was measured using 320-row multidetector computed tomography. The high EATV group showed specific cardiometabolic derangements as well as left atrial dilatation and left ventricular dysfunction. Multivariate regression analysis showed that the EATVI was an independent predictor of recurrent AF after catheter ablation. High EATV (EATVI ≥ 85 mL/m2 ) or EATVI cutoff ≥116 mL/m2 can predict recurrent AF after catheter ablation, independent of other risk factors. In conclusion, EATVI was an independent predictor of recurrent AF after catheter ablation; a high EATV tertile or EATVI cutoff may be useful for prediction of recurrent AF after catheter ablation. Future studies should determine the utility of the EATVI in the clinical setting of AF ablation., (Copyright © 2018. Published by Elsevier Inc.)- Published
- 2018
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5. Effect of the Epicardial Adipose Tissue Volume on the Prevalence of Paroxysmal and Persistent Atrial Fibrillation.
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Oba K, Maeda M, Maimaituxun G, Yamaguchi S, Arasaki O, Fukuda D, Yagi S, Hirata Y, Nishio S, Iwase T, Takao S, Kusunose K, Yamada H, Soeki T, Wakatsuki T, Harada M, Masuzaki H, Sata M, and Shimabukuro M
- Subjects
- Aged, Coronary Angiography methods, Female, Humans, Male, Middle Aged, Multidetector Computed Tomography methods, Obesity, Prevalence, Retrospective Studies, Risk Factors, Adipose Tissue pathology, Atrial Fibrillation etiology, Pericardium cytology
- Abstract
Background: Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with atrial fibrillation (AF), it is controversial whether there is a dose-response relationship of increasing EATV along the continuum of AF. We evaluated the effect of the EATV on the prevalence of paroxysmal AF (PAF) and persistent AF (PeAF) and the relationships with cardiac structure and functional remodeling.Methods and Results:Subjects who underwent multidetector computed tomography (MDCT) coronary angiography because of symptoms suggestive of coronary artery disease were divided into sinus rhythm (SR) (n=112), PAF (n=133), and PeAF (n=71) groups. The EATV index (EATV/body surface area, mL/m
2 ) was strongly associated with the prevalence of PAF and PeAF on the model adjusted for known AF risk factors. The effect of the EATV index on the prevalence of PeAF, but not on that of PAF, was modified by the left atrial (LA) dimension, suggesting that extension of the LA dimension is related to EATV expansion in PeAF. The cutoff value of the EATV index for the prevalence was higher in PeAF than in PAF (64 vs. 55 mL/m2 , P<0.01)., Conclusions: The EATV index is associated with the prevalence of PAF and PeAF, and its cutoff values are predictive for PAF and PeAF development independently of other AF risk factors.- Published
- 2018
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6. Local Thickness of Epicardial Adipose Tissue Surrounding the Left Anterior Descending Artery Is a Simple Predictor of Coronary Artery Disease - New Prediction Model in Combination With Framingham Risk Score.
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Maimaituxun G, Shimabukuro M, Fukuda D, Yagi S, Hirata Y, Iwase T, Takao S, Matsuura T, Ise T, Kusunose K, Tobiume T, Yamaguchi K, Yamada H, Soeki T, Wakatsuki T, Harada M, and Sata M
- Subjects
- Adipose Tissue physiopathology, Aged, Aged, 80 and over, Coronary Artery Disease physiopathology, Coronary Stenosis physiopathology, Coronary Vessels physiopathology, Female, Humans, Male, Middle Aged, Pericardium physiopathology, Adipose Tissue diagnostic imaging, Coronary Artery Disease diagnostic imaging, Coronary Stenosis diagnostic imaging, Coronary Vessels diagnostic imaging, Magnetic Resonance Imaging, Pericardium diagnostic imaging
- Abstract
Background: Compared with global cardiac adiposity, the local accumulation of fat surrounding coronary arteries might have a more direct impact on coronary artery disease (CAD). Here, we compared the local epicardial adipose tissue (EAT) thickness and global cardiac adiposity volumes for predicting CAD.Methods and Results:A total of 197 consecutive subjects underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into CAD (≥1 coronary artery branch stenosis ≥50%) and non-CAD groups. EAT thickness was measured at the right coronary artery (EAT
RCA ), the left anterior descending artery (EATLAD ), and the left circumflex artery (EATLCX ). Although EATRCA and EATLCX were similar between the 2 groups, EATLAD was larger in the CAD group than in the non-CAD group (5.45±2.16 mm vs. 6.86±2.19 mm, P<0.001). EATLAD , after correcting for confounding factors, was strongly associated with CAD (r=0.276, P<0.001) and Gensini score (r=0.239, P<0.001). On multiple regression analysis, Framingham risk score combined with EATLAD was a strong predictor of CAD (adjusted R2 =0.121; P<0.001)., Conclusions: The local fat thickness surrounding the LAD is a simple and useful surrogate marker for estimating the presence, severity, and extent of CAD, independent of classical cardiovascular risk factors.- Published
- 2018
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7. Echocardiographic Epicardial Adipose Tissue Thickness Is Associated with Symptomatic Coronary Vasospasm during Provocative Testing.
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Nishio S, Kusunose K, Yamada H, Hirata Y, Ise T, Yamaguchi K, Yagi S, Soeki T, Wakatsuki T, Shimabukuro M, and Sata M
- Subjects
- Aged, Cardiovascular Agents administration & dosage, Female, Hospitals, University, Humans, Male, Middle Aged, Predictive Value of Tests, Retrospective Studies, Risk Factors, Sensitivity and Specificity, Acetylcholine administration & dosage, Adipose Tissue diagnostic imaging, Coronary Artery Disease diagnostic imaging, Coronary Vasospasm chemically induced, Coronary Vasospasm diagnostic imaging, Echocardiography methods, Pericardium diagnostic imaging
- Abstract
Background: Epicardial adipose tissue (EAT) is the ectopic visceral fat surrounding the heart, which plays an important role in atherosclerosis of the coronary arteries via endothelial damage. Several studies have also suggested that vasospasm with angina (VSA) causes endothelial dysfunction in the coronary arteries. The aim of this study was to evaluate the thickness of EAT in the anterior interventricular groove (EAT-AIG) using echocardiography in patients who had no obstructive coronary artery disease and were suspected of having VSA., Methods: Sixty-five patients who underwent intracoronary acetylcholine provocation testing for clinical indications were prospectively enrolled. VSA was diagnosed by coronary artery stenosis increase of >90% and the presentation of chest pain with ischemic changes on electrocardiography., Results: Subjects were divided into two groups, with and without significant coronary spasm (VSA group, 30 patients; non-VSA group, 35 patients), consistent with acetylcholine provocation testing. EAT-AIG thickness was significantly greater in the VSA group than in the non-VSA group (8.2 ± 2.7 vs 6.1 ± 2.5 mm, P = .002). By receiver operating characteristic analysis, EAT-AIG thickness had a high C statistic (area under the curve = 0.81, P < .001) after adjustment for conventional risk factors (smoking, diabetes mellitus, and dyslipidemia). EAT-AIG thickness had incremental diagnostic value over other conventional risk factors (area under the curve = 0.81 vs 0.64, P for comparison = .020)., Conclusions: EAT-AIG thickness, which is noninvasively and easily measured using transthoracic echocardiography, can be one of multiple clinical variables associated with VSA., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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8. Teneligliptin, a dipeptidyl peptidase-4 inhibitor, attenuated pro-inflammatory phenotype of perivascular adipose tissue and inhibited atherogenesis in normoglycemic apolipoprotein-E-deficient mice.
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Salim HM, Fukuda D, Higashikuni Y, Tanaka K, Hirata Y, Yagi S, Soeki T, Shimabukuro M, and Sata M
- Subjects
- 3T3-L1 Cells, Adipose Tissue enzymology, Adipose Tissue pathology, Animals, Aorta enzymology, Aorta pathology, Aorta physiopathology, Aortic Diseases enzymology, Aortic Diseases genetics, Aortic Diseases pathology, Apolipoproteins E genetics, Atherosclerosis enzymology, Atherosclerosis genetics, Atherosclerosis pathology, Cytokines genetics, Disease Models, Animal, Exenatide, Female, Genetic Predisposition to Disease, Incretins pharmacology, Macrophage Activation drug effects, Macrophages drug effects, Macrophages enzymology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Oxidative Stress drug effects, Peptides pharmacology, Phenotype, Plaque, Atherosclerotic, RAW 264.7 Cells, Signal Transduction drug effects, Time Factors, Vasodilation drug effects, Venoms pharmacology, Adipose Tissue drug effects, Anti-Inflammatory Agents pharmacology, Aorta drug effects, Aortic Diseases prevention & control, Apolipoproteins E deficiency, Atherosclerosis prevention & control, Cytokines metabolism, Dipeptidyl Peptidase 4 metabolism, Dipeptidyl-Peptidase IV Inhibitors pharmacology, Inflammation Mediators metabolism, Pyrazoles pharmacology, Thiazolidines pharmacology
- Abstract
Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether teneligliptin alters the pro-inflammatory phenotype of perivascular adipose tissue (PVAT) and inhibits atherogenesis., Methods and Results: Teneligliptin (60mg/kg/day) was administered orally to apolipoprotein-E-deficient (ApoE
-/- ) mice for 20weeks. Teneligliptin significantly inhibited the development of atherosclerosis in the aortic arch compared with vehicle (P<0.05), without alteration of blood glucose level or blood pressure. Histological analyses demonstrated that teneligliptin decreased lipid deposition and MCP-1 expression (P<0.05, respectively), and tended to decrease macrophage accumulation in atherosclerotic plaques. The results of quantitative RT-PCR analysis demonstrated that teneligliptin reduced the expression of inflammatory molecules such as TNF-α and MCP-1 in the abdominal aorta. Furthermore, teneligliptin reduced the expression of a macrophage marker and Nox-4, a major NADPH oxidase subunit in adipocytes, in PVAT around the aortic arch. Administration of teneligliptin for 8weeks ameliorated endothelium-dependent vasodilation and reduced oxidative stress as determined by urinary 8-OHdG excretion (P<0.05) compared with vehicle. In vitro experiments demonstrated that exendin-4 (Ex-4), a GLP-1 analog, decreased the expression of inflammatory molecules in RAW264.7 cells. Also, Ex-4 decreased Nox4 expression in 3T3-L1 adipocytes., Conclusion: Teneligliptin inhibited atherogenesis with attenuation of the inflammatory phenotype in PVAT. A GLP-1 analog suppressed pro-inflammatory activation of macrophages and adipocytes. Suppression of the pro-inflammatory phenotype of PVAT might contribute, at least partially, to the cardioprotective effects of teneligliptin., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2017
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9. Gender-linked impact of epicardial adipose tissue volume in patients who underwent coronary artery bypass graft surgery or non-coronary valve surgery.
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Maimaituxun G, Shimabukuro M, Salim HM, Tabata M, Yuji D, Morimoto Y, Akasaka T, Matsuura T, Yagi S, Fukuda D, Yamada H, Soeki T, Sugimoto T, Tanaka M, Takanashi S, and Sata M
- Subjects
- Aged, Female, Humans, Male, Multivariate Analysis, Organ Size, Regression Analysis, Adipose Tissue pathology, Coronary Artery Bypass, Heart Valves surgery, Pericardium pathology, Sex Characteristics
- Abstract
Background: Traditional and non-traditional risk factors for atherosclerotic cardiovascular disease (ASCVD) are different between men and women. Gender-linked impact of epicardial adipose tissue volume (EATV) in patients undergoing coronary artery bypass grafting (CABG) remains unknown., Methods: Gender-linked impact of EATV, abdominal fat distribution and other traditional ASCVD risk factors were compared in 172 patients (men: 115; women: 57) who underwent CABG or non-coronary valvular surgery (non-CABG)., Results: In men, EATV, EATV index (EATV/body surface area) and the markers of adiposity such as body mass index, waist circumference and visceral fat area were higher in the CABG group than in the non-CABG group. Traditional ASCVD risk factors were also prevalent in the CABG group. In women, EATV and EATV index were higher in the CABG group, but other adiposity markers were comparable between CABG and non-CABG groups. Multivariate logistic regression analysis showed that in men, CABG was determined by EATV Index and other ASCVD risk factors including hypertension, dyslipidemia, adiponectin, high sensitive C-reactive protein (hsCRP) and type 2 diabetes mellitus (Corrected R2 = 0.262, p < 0.0001), while in women, type 2 diabetes mellitus is a single strong predictor for CABG, excluding EATV Index (Corrected R2 = 0.266, p = 0.005)., Conclusions: Our study found that multiple risk factors, including epicardial adipose tissue volume and traditional ASCVD factors are determinants for CABG in men, but type 2 diabetes mellitus was the sole determinant in women. Gender-specific disparities in risk factors of CABG prompt us to evaluate new diagnostic and treatment strategies and to seek underlying mechanisms.
- Published
- 2017
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10. Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance.
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Nishimoto S, Fukuda D, Higashikuni Y, Tanaka K, Hirata Y, Murata C, Kim-Kaneyama JR, Sato F, Bando M, Yagi S, Soeki T, Hayashi T, Imoto I, Sakaue H, Shimabukuro M, and Sata M
- Subjects
- Adipocytes drug effects, Adipose Tissue drug effects, Adult, Aged, Animals, Bone Marrow metabolism, Bone Marrow pathology, Cell Communication, DNA blood, Female, Gene Deletion, Gene Expression, Humans, Insulin Resistance genetics, Macrophages metabolism, Male, Mice, Mice, Knockout, Middle Aged, Obesity genetics, Obesity pathology, Panniculitis genetics, Panniculitis pathology, Signal Transduction, Toll-Like Receptor 9 antagonists & inhibitors, Toll-Like Receptor 9 genetics, Toll-Like Receptor 9 metabolism, Adipocytes metabolism, Adipose Tissue metabolism, DNA metabolism, Obesity metabolism, Panniculitis metabolism
- Abstract
Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed increased release of cfDNA, as determined by the concentrations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in plasma. cfDNA released from degenerated adipocytes promoted monocyte chemoattractant protein-1 (MCP-1) expression in wild-type macrophages, but not in TLR9-deficient (Tlr9 (-/-) ) macrophages. Fat-fed Tlr9 (-/-) mice demonstrated reduced macrophage accumulation and inflammation in adipose tissue and better insulin sensitivity compared with wild-type mice, whereas bone marrow reconstitution with wild-type bone marrow restored the attenuation of insulin resistance observed in fat-fed Tlr9 (-/-) mice. Administration of a TLR9 inhibitory oligonucleotide to fat-fed wild-type mice reduced the accumulation of macrophages in adipose tissue and improved insulin resistance. Furthermore, in humans, plasma ssDNA level was significantly higher in patients with computed tomography-determined visceral obesity and was associated with homeostasis model assessment of insulin resistance (HOMA-IR), which is the index of insulin resistance. Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance.
- Published
- 2016
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11. Clinical Utility of Measuring Epicardial Adipose Tissue Thickness with Echocardiography Using a High-Frequency Linear Probe in Patients with Coronary Artery Disease.
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Hirata Y, Yamada H, Kusunose K, Iwase T, Nishio S, Hayashi S, Bando M, Amano R, Yamaguchi K, Soeki T, Wakatsuki T, and Sata M
- Subjects
- Adiposity, Age Distribution, Aged, Cohort Studies, Coronary Angiography methods, Coronary Disease physiopathology, Female, Humans, Incidence, Male, Middle Aged, Prognosis, Prospective Studies, ROC Curve, Risk Assessment, Sex Distribution, Adipose Tissue diagnostic imaging, Coronary Disease diagnostic imaging, Echocardiography methods, Multidetector Computed Tomography methods, Pericardium diagnostic imaging
- Abstract
Background: The relationship between epicardial adipose tissue (EAT) and coronary artery disease (CAD) has recently attracted a great deal of attention in the medical community. The objective of this study was to determine whether measuring EAT thickness in the anterior interventricular groove (AIG) using echocardiography is feasible and whether this index can be a marker of CAD., Methods: A total of 311 patients (mean age, 67 ± 11 years; 208 men) who underwent coronary angiography between December 2011 and December 2013 were prospectively enrolled. EAT-AIG thickness and EAT thickness on the free wall of the right ventricle (RV) were measured in systole using a high-frequency linear probe. Seventy-one patients who underwent multidetector-row computed tomography were enrolled to validate the method for measuring EAT thickness using echocardiography. Subjects were divided into two groups, those with and without significant coronary stenosis, on the basis of findings on coronary angiography (≥ 75% luminal narrowing)., Results: EAT-AIG thickness measured using echocardiography was validated by computed tomography. EAT-AIG thickness was strongly correlated with EAT volume (r = 0.714, P < .001). The CAD group had thicker EAT-AIG than the non-CAD group (8.3 ± 3.0 vs 6.3 ± 2.5 mm, P < .001). EAT-RV thickness was greater in the CAD group than in the non-CAD group (5.0 ± 2.1 vs 4.4 ± 2.3 mm, P = .009) as well. The area under the curve on receiver operating characteristic curve analysis of EAT-AIG thickness for predicting CAD was 0.704, which was higher than the EAT-RV thickness., Conclusions: Measuring EAT thickness using echocardiography with a high-frequency linear probe was validated with computed tomography. EAT-AIG was thicker in the CAD group than in the non-CAD group, as was EAT-RV thickness. This noninvasive index may have potential as a diagnostic marker for predicting coronary atherosclerosis., (Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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12. Expression of NLRP3 in subcutaneous adipose tissue is associated with coronary atherosclerosis.
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Bando S, Fukuda D, Soeki T, Nishimoto S, Uematsu E, Matsuura T, Ise T, Tobiume T, Yamaguchi K, Yagi S, Iwase T, Yamada H, Wakatsuki T, Shimabukuro M, and Sata M
- Subjects
- Adipose Tissue pathology, Aged, Biomarkers, Cardiac Resynchronization Therapy, Constriction, Pathologic physiopathology, Coronary Vessels pathology, Defibrillators, Implantable, Female, Humans, Inflammasomes, Life Style, Macrophages cytology, Male, Middle Aged, Multivariate Analysis, NLR Family, Pyrin Domain-Containing 3 Protein, Pacemaker, Artificial, Risk Factors, Severity of Illness Index, Subcutaneous Fat pathology, Uric Acid blood, Adiponectin blood, Adipose Tissue metabolism, Carrier Proteins metabolism, Coronary Artery Disease metabolism, Gene Expression Regulation
- Abstract
Objectives: The promotion of adipose tissue inflammation by lifestyle-related diseases such as obesity and diabetes accelerates atherogenesis; however, the underlying mechanisms remain incompletely understood. Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome contributes to chronic inflammation in adipose tissue. Here, we investigated the link between NLRP3 expression in subcutaneous adipose tissue (SAT) and the severity of coronary atherosclerosis., Methods and Results: SAT was obtained from 72 patients who underwent heart device implantation and coronary angiography. Expression of NLRP3 inflammasome-related molecules (NLRP3, IL-1β and IL-18) in SAT were evaluated by quantitative RT-PCR. Laboratory markers related to lifestyle-related diseases were measured. Patients with obesity, dyslipidemia (P < 0.05, respectively), diabetes or hyperuricemia (P < 0.01, respectively) had significantly higher expression of NLRP3. Multivariate analysis demonstrated that body mass index and serum level of uric acid were predictors of NLRP3 expression in SAT. The expression of NLRP3 in SAT correlated negatively with serum adiponectin level (r = -0.23, P < 0.05). Patients with coronary artery disease showed higher NLRP3 expression than patients without significant stenosis (P < 0.01). Furthermore, the expression of NLRP3 in SAT correlated positively with the severity of coronary atherosclerosis as determined by Gensini score (r = 0.47, P < 0.0001) or SYNTAX score (r = 0.55, P < 0.0001). Multiple regression analysis revealed that the expression of NLRP3 in SAT remains as an independent predictors for the severity of coronary atherosclerosis., Conclusions: The expression of NLRP3 in SAT, which is affected by lifestyle-related diseases, is associated with the severity of coronary atherosclerosis. Our results suggest that NLRP3 inflammasome in SAT may have a role in atherogenesis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2015
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13. Role of pericardial fat: The good, the bad and the ugly.
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Yamada H and Sata M
- Subjects
- Adipose Tissue diagnostic imaging, Adipose Tissue pathology, Coronary Artery Disease diagnosis, Coronary Artery Disease etiology, Coronary Artery Disease metabolism, Echocardiography, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multidetector Computed Tomography, Risk, Adipose Tissue metabolism, Adipose Tissue physiology, Pericardium metabolism
- Published
- 2015
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14. MicroRNA-378 regulates adiponectin expression in adipose tissue: a new plausible mechanism.
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Ishida M, Shimabukuro M, Yagi S, Nishimoto S, Kozuka C, Fukuda D, Soeki T, Masuzaki H, Tsutsui M, and Sata M
- Subjects
- 3' Untranslated Regions genetics, 3T3-L1 Cells, Adipocytes drug effects, Adipocytes metabolism, Adipose Tissue cytology, Animals, Base Sequence, Gene Expression Regulation drug effects, HEK293 Cells, Humans, Mice, Mutagenesis, Site-Directed, Tumor Necrosis Factor-alpha pharmacology, Adiponectin genetics, Adipose Tissue metabolism, Gene Expression Regulation genetics, MicroRNAs genetics
- Abstract
Aims: Mechanisms regulating adiponectin expression have not been fully clarified. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, are involved in biological processes, including obesity and insulin resistance. We evaluated whether the miRNA-378 pathway is involved in regulating adiponectin expression., Methods and Results: First, we determined a putative target site for miRNA-378 in the 3 prime untranslated region (3'UTR) of the adiponectin gene by in silico analysis. The levels of adiponectin mRNA and protein were decreased in 3T3-L1 cells overexpressing the mimic of miRNA-378. Luminescence activity in HEK293T cells expressing a renilla-luciferase-adiponectin-3'UTR sequence was inhibited by overexpressing the mimic of miRNA-378, and the decrease was reversed by adding the inhibitor of miRNA-378. Moreover, we confirmed the inhibitory effects of the mimic were cancelled in a deleted mutant of the miR-378 3'-UTR binding site. Addition of tumor necrosis factor-α (TNFα) led a upregulation of miR-378 and downregulation of adiponectin at mRNA and protein levels in 3T3-L1 cells. Level of miR-378 was higher and mRNA level of adiponectin was lower in diabetic ob/ob mice than those of normal C57BL/6 mice and levels of miR378 and adiponectin were negatively well correlated (r = -0.624, p = 0.004)., Conclusions: We found that levels of miRNA-378 could modulate adiponectin expression via the 3'UTR sequence-binding site. Our findings warrant further investigations into the role of miRNAs in regulating the adiponectin expression.
- Published
- 2014
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15. Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis.
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Shimabukuro M, Hirata Y, Tabata M, Dagvasumberel M, Sato H, Kurobe H, Fukuda D, Soeki T, Kitagawa T, Takanashi S, and Sata M
- Subjects
- Aged, Antigens, CD analysis, Antigens, Differentiation, Myelomonocytic analysis, CD11c Antigen analysis, Cholesterol, HDL blood, Coronary Artery Disease metabolism, Coronary Artery Disease pathology, Female, Humans, Logistic Models, Male, Middle Aged, Adipokines metabolism, Adipose Tissue pathology, Coronary Artery Disease etiology, Pericardium pathology
- Abstract
Objective: The impact of epicardial adipose tissue (EAT) over abdominal or overall adiposity on coronary artery disease (CAD) is currently unknown. We compared the association among EAT volume (EATV), cytokine/adipocytokine profiles in EAT and subcutaneous fat, and atherogenic CAD., Approach and Results: Paired samples were obtained from EAT and subcutaneous adipose tissue during elective cardiac surgery for CAD (n=50) or non-CAD (n=50). EATV was the sum of cross-sectional EAT areas, and visceral and subcutaneous fat areas were determined at the umbilicus level on computed tomography scans. CD68(+), CD11c(+), and CD206(+) cells were counted using immunohistochemical staining. Cytokine/adipocytokine expression was evaluated using quantitative real-time polymerase chain reaction. Multivariate analysis indicated that male sex, age, diabetes mellitus, high triglycerides, and low high-density lipoprotein cholesterol, and EATV index (EATV/body surface area, cm(3)/m(2)) were significant CAD predictors (corrected R(2)=0.401; P<0.001); visceral fat area, hypertension, smoking, low-density lipoprotein cholesterol (140 mg/dL [3.63 mmol/L]) or statin use were not predictors. The EATV index positively correlated with the CD68(+) and CD11c(+) cell numbers and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), interleukin-1β, and interleukin-1R expression; and negatively correlated with adiponectin expression in EAT. A multivariate analysis model, including CD68(+) cells and interleukin-1β, and adiponectin expression in EAT strongly predicted CAD (corrected R(2)=0.756; P<0.001)., Conclusions: EATV and macrophage and cytokine/adipocytokine signals in EAT strongly correlated with CAD. Our findings suggest that EATV and adipocytokine imbalance are strongly linked to human coronary atherosclerosis.
- Published
- 2013
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16. Perivascular adipose tissue-secreted angiopoietin-like protein 2 (Angptl2) accelerates neointimal hyperplasia after endovascular injury.
- Author
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Tian Z, Miyata K, Tazume H, Sakaguchi H, Kadomatsu T, Horio E, Takahashi O, Komohara Y, Araki K, Hirata Y, Tabata M, Takanashi S, Takeya M, Hao H, Shimabukuro M, Sata M, Kawasuji M, and Oike Y
- Subjects
- Adiponectin metabolism, Adolescent, Adult, Aged, Aged, 80 and over, Angiopoietin-Like Protein 2, Angiopoietin-like Proteins, Angiopoietins genetics, Animals, Child, Coronary Artery Disease metabolism, Coronary Artery Disease pathology, Coronary Vessels metabolism, Cytokines genetics, Cytokines metabolism, Female, Femoral Artery metabolism, Femoral Artery pathology, Gene Expression, Humans, Hypercholesterolemia metabolism, Hypercholesterolemia pathology, Hyperplasia, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Neointima pathology, Transcriptional Activation, Vascular System Injuries pathology, Adipose Tissue metabolism, Angiopoietins metabolism, Neointima metabolism, Vascular System Injuries metabolism
- Abstract
Much attention is currently focused on the role of perivascular adipose tissue in development of cardiovascular disease (CVD). Some researchers view it as promoting CVD through secretion of cytokines and growth factors called adipokines, while recent reports reveal that perivascular adipose tissue can exert a protective effect on CVD development. Furthermore, adiponectin, an anti-inflammatory adipokine, reportedly suppresses neointimal hyperplasia after endovascular injury, whereas such vascular remodeling is enhanced by pro-inflammatory adipokines secreted by perivascular adipose, such as tumor necrosis factor-α (TNF-α). These findings suggest that extent of vascular remodeling, a pathological process associated with CVD development, depends on the balance between pro- and anti-inflammatory adipokines secreted from perivascular adipose tissue. We previously demonstrated that angiopoietin-like protein 2 (Angptl2), a pro-inflammatory factor secreted by adipose tissue, promotes adipose tissue inflammation and subsequent systemic insulin resistance in obesity. Here, we examined whether Angptl2 secreted by perivascular adipose tissue contributes to vascular remodeling after endovascular injury in studies of transgenic mice expressing Angptl2 in adipose tissue (aP2-Angptl2 transgenic mice) and Angptl2 knockout mice (Angptl2(-/-) mice). To assess the role of Angptl2 secreted by perivascular adipose tissue on vascular remodeling after endovascular injury, we performed adipose tissue transplantation experiments using these mice. Wild-type mice with perivascular adipose tissue derived from aP2-Angptl2 mice exhibited accelerated neointimal hyperplasia after endovascular injury compared to wild-type mice transplanted with wild-type tissue. Conversely, vascular inflammation and neointimal hyperplasia after endovascular injury were significantly attenuated in wild-type mice transplanted with Angptl2(-/-) mouse-derived perivascular adipose tissue compared to wild-type mice transplanted with wild-type tissue. RT-PCR analysis revealed that mouse Angptl2 expression in perivascular adipose tissue was significantly increased by aging, hypercholesterolemia, and endovascular injury, all risk factors for coronary heart disease (CHD). Immunohistochemical and RT-PCR analysis of tissues from patients with CHD and from non-CHD patients indicated that ANGPTL2 expression in epicardial adipose tissue was unchanged. Interestingly, that analysis also revealed a positive correlation in ANGPTL2 and ADIPONECTIN expression in epicardial adipose tissue of non-CHD patients, a correlation not seen in CHD patients. However, in epicardial adipose tissue from CHD patients, ANGPTL2 expression was positively correlated with that of TNF-α, a correlation was not seen in non-CHD patients. These findings suggest that pro-inflammatory adipokines cooperatively accelerate CHD development and that maintaining a balance between pro- and anti-inflammatory adipokines likely protects non-CHD patients from developing CHD. Overall, our studies demonstrate that perivascular adipose tissue-secreted Angptl2 accelerates vascular inflammation and the subsequent CVD development., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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17. Gender disparities in the association between epicardial adipose tissue volume and coronary atherosclerosis: a 3-dimensional cardiac computed tomography imaging study in Japanese subjects.
- Author
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Dagvasumberel M, Shimabukuro M, Nishiuchi T, Ueno J, Takao S, Fukuda D, Hirata Y, Kurobe H, Soeki T, Iwase T, Kusunose K, Niki T, Yamaguchi K, Taketani Y, Yagi S, Tomita N, Yamada H, Wakatsuki T, Harada M, Kitagawa T, and Sata M
- Subjects
- Age Factors, Aged, Body Surface Area, Chi-Square Distribution, Coronary Artery Disease ethnology, Coronary Stenosis ethnology, Female, Humans, Japan epidemiology, Logistic Models, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Risk Assessment, Risk Factors, Severity of Illness Index, Sex Factors, Adipose Tissue diagnostic imaging, Asian People, Coronary Angiography methods, Coronary Artery Disease diagnostic imaging, Coronary Stenosis diagnostic imaging, Health Status Disparities, Multidetector Computed Tomography, Pericardium diagnostic imaging
- Abstract
Background: Growing evidence suggests that epicardial adipose tissue (EAT) may contribute to the development of coronary artery disease (CAD). In this study, we explored gender disparities in EAT volume (EATV) and its impact on coronary atherosclerosis., Methods: The study population consisted of 90 consecutive subjects (age: 63 ± 12 years; men: 47, women: 43) who underwent 256-slice multi-detector computed tomography (MDCT) coronary angiography. EATV was measured as the sum of cross-sectional epicardial fat area on CT images, from the lower surface of the left pulmonary artery origin to the apex. Subjects were segregated into the CAD group (coronary luminal narrowing > 50%) and non-CAD group., Results: EATV/body surface area (BSA) was higher among men in the CAD group than in the non-CAD group (62 ± 13 vs. 33 ± 10 cm3/m2, p < 0.0001), but did not differ significantly among women in the 2 groups (49 ± 18 vs. 42 ± 9 cm3/m2, not significant). Multivariate logistic analysis showed that EATV/BSA was the single predictor for >50% coronary luminal narrowing in men (p < 0.0001). Predictors excluded were age, body mass index, hypertension, diabetes mellitus, and hyperlipidemia., Conclusions: Increased EATV is strongly associated with coronary atherosclerosis in men.
- Published
- 2012
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18. The radioprotective 105/MD-1 complex contributes to diet-induced obesity and adipose tissue inflammation.
- Author
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Watanabe Y, Nakamura T, Ishikawa S, Fujisaka S, Usui I, Tsuneyama K, Ichihara Y, Wada T, Hirata Y, Suganami T, Izaki H, Akira S, Miyake K, Kanayama HO, Shimabukuro M, Sata M, Sasaoka T, Ogawa Y, Tobe K, Takatsu K, and Nagai Y
- Subjects
- Adipocytes cytology, Adipocytes metabolism, Adipose Tissue pathology, Animals, Antigens, CD genetics, Antigens, Surface genetics, Coculture Techniques, Dietary Fats administration & dosage, Epididymis, Fatty Liver etiology, Gene Expression Regulation physiology, Humans, Inflammation metabolism, Insulin Resistance, Macrophages cytology, Macrophages metabolism, Male, Membrane Glycoproteins genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Palmitic Acid, Stearic Acids, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 metabolism, Adipose Tissue metabolism, Antigens, CD metabolism, Antigens, Surface metabolism, Dietary Fats adverse effects, Inflammation etiology, Membrane Glycoproteins metabolism, Obesity etiology
- Abstract
Recent accumulating evidence suggests that innate immunity is associated with obesity-induced chronic inflammation and metabolic disorders. Here, we show that a Toll-like receptor (TLR) protein, radioprotective 105 (RP105)/myeloid differentiation protein (MD)-1 complex, contributes to high-fat diet (HFD)-induced obesity, adipose tissue inflammation, and insulin resistance. An HFD dramatically increased RP105 mRNA and protein expression in stromal vascular fraction of epididymal white adipose tissue (eWAT) in wild-type (WT) mice. RP105 mRNA expression also was significantly increased in the visceral adipose tissue of obese human subjects relative to nonobese subjects. The RP105/MD-1 complex was expressed by most adipose tissue macrophages (ATMs). An HFD increased RP105/MD-1 expression on the M1 subset of ATMs that accumulate in eWAT. Macrophages also acquired this characteristic in coculture with 3T3-L1 adipocytes. RP105 knockout (KO) and MD-1 KO mice had less HFD-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance compared with wild-type (WT) and TLR4 KO mice. Finally, the saturated fatty acids, palmitic and stearic acids, are endogenous ligands for TLR4, but they did not activate RP105/MD-1. Thus, the RP105/MD-1 complex is a major mediator of adipose tissue inflammation independent of TLR4 signaling and may represent a novel therapeutic target for obesity-associated metabolic disorders.
- Published
- 2012
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19. Role of epicardial adipose tissue in atrial fibrillation.
- Author
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Soeki T and Sata M
- Subjects
- Female, Humans, Male, Adipose Tissue diagnostic imaging, Atrial Fibrillation etiology, Coronary Artery Disease diagnostic imaging, Multidetector Computed Tomography, Pericardium diagnostic imaging
- Published
- 2012
- Full Text
- View/download PDF
20. [Role of chronic inflammation in the pathogenesis of atherosclerosis].
- Author
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Sata M
- Subjects
- Adipokines metabolism, Adipose Tissue metabolism, Angiotensin II physiology, Animals, Chronic Disease, Coronary Vessels metabolism, Cytokines metabolism, Humans, Inflammation Mediators metabolism, Life Style, Macrophages physiology, Neovascularization, Pathologic, Plaque, Atherosclerotic etiology, Vascular Endothelial Growth Factor A physiology, Adipose Tissue physiology, Atherosclerosis etiology, Inflammation etiology
- Published
- 2011
- Full Text
- View/download PDF
21. Coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue.
- Author
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Hirata Y, Tabata M, Kurobe H, Motoki T, Akaike M, Nishio C, Higashida M, Mikasa H, Nakaya Y, Takanashi S, Igarashi T, Kitagawa T, and Sata M
- Subjects
- Aged, Antigens, CD analysis, Antigens, Differentiation, Myelomonocytic analysis, CD11c Antigen analysis, Chemokine CCL2 metabolism, Cytokines metabolism, Female, Humans, Immunohistochemistry, Inflammation pathology, Interleukin-6 metabolism, Lectins, C-Type analysis, Macrophages metabolism, Male, Mannose Receptor, Mannose-Binding Lectins analysis, Receptors, Cell Surface analysis, Subcutaneous Fat pathology, Adipose Tissue pathology, Coronary Artery Disease pathology, Macrophages pathology, Pericardium pathology
- Abstract
Objectives: The purpose of this report was to assess the link between macrophage polarization in epicardial adipose tissue and atherosclerosis in patients with coronary artery disease (CAD)., Background: Macrophage accumulation enhances chronic inflammation in adipose tissue, but macrophage phenotypic change in human epicardial adipose tissue and its role in atherogenesis are unknown., Methods: Samples were obtained from epicardial and subcutaneous adipose tissue during elective cardiac surgery (CAD, n = 38; non-CAD, n = 40). Infiltration of M1/M2 macrophages was investigated by immunohistochemical staining with antibodies against CD11c and CD206, respectively. Expression of pro- and anti-inflammatory adipocytokines in adipose tissue was evaluated by real-time quantitative polymerase chain reaction., Results: Infiltration of macrophages and expression of pro- and anti-inflammatory cytokines were enhanced in epicardial fat of patients with CAD compared with that in non-CAD patients (p < 0.05). The ratio of M1/M2 macrophages was positively correlated with the severity of CAD (r = 0.312, p = 0.039). Furthermore, the expression of pro-inflammatory cytokines was positively correlated, and the expression of anti-inflammatory cytokines was negatively correlated with the ratio of M1/M2 macrophages in epicardial adipose tissue of CAD patients. By contrast, there was no significant difference in macrophage infiltration and cytokine expression in subcutaneous adipose tissue between the CAD and non-CAD groups., Conclusions: The ratio of M1/M2 macrophages in epicardial adipose tissue of CAD patients is changed compared with that in non-CAD patients. Human coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
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22. [Obesity: Progress in diagnosis and treatment topics, IV. Recent topics; 1. Ectopic fat disposition and lipotoxicity].
- Author
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Shimabukuro M, Yamakawa K, Masuzaki H, and Sata M
- Subjects
- Fatty Acids, Nonesterified metabolism, Humans, Adipose Tissue pathology, Obesity pathology
- Published
- 2011
- Full Text
- View/download PDF
23. Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans.
- Author
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Ichioka M, Suganami T, Tsuda N, Shirakawa I, Hirata Y, Satoh-Asahara N, Shimoda Y, Tanaka M, Kim-Saijo M, Miyamoto Y, Kamei Y, Sata M, and Ogawa Y
- Subjects
- 3T3-L1 Cells, Adipose Tissue drug effects, Analysis of Variance, Animals, Blotting, Western, Cells, Cultured, Humans, Inflammation genetics, Inflammation metabolism, Lectins, C-Type genetics, Linear Models, Macrophages cytology, Macrophages drug effects, Male, Membrane Proteins genetics, Mice, NF-kappa B genetics, NF-kappa B metabolism, Obesity genetics, Palmitic Acid pharmacology, RNA, Messenger genetics, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction physiology, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 metabolism, Adipose Tissue metabolism, Lectins, C-Type metabolism, Macrophages metabolism, Membrane Proteins metabolism, Obesity metabolism
- Abstract
Objective: We have provided evidence that saturated fatty acids, which are released from adipocytes via macrophage-induced adipocyte lipolysis, serve as a naturally occurring ligand for the Toll-like receptor (TLR) 4 complex in macrophages, thereby aggravating obesity-induced adipose tissue inflammation. The aim of this study was to identify the molecule(s) activated in adipose tissue macrophages in obesity., Research Design and Methods: We performed a cDNA microarray analysis of coculture of 3T3-L1 adipocytes and RAW264 macrophages. Cultured adipocytes and macrophages and the adipose tissue of obese mice and humans were used to examine mRNA and protein expression., Results: We found that macrophage-inducible C-type lectin (Mincle; also called Clec4e and Clecsf9), a type II transmembrane C-type lectin, is induced selectively in macrophages during the interaction between adipocytes and macrophages. Treatment with palmitate, a major saturated fatty acid released from 3T3-L1 adipocytes, induced Mincle mRNA expression in macrophages at least partly through the TLR4/nuclear factor (NF)-κB pathway. Mincle mRNA expression was increased in parallel with macrophage markers in the adipose tissue of obese mice and humans. The obesity-induced increase in Mincle mRNA expression was markedly attenuated in C3H/HeJ mice with defective TLR4 signaling relative to control C3H/HeN mice. Notably, Mincle mRNA was expressed in bone-marrow cell (BMC)-derived proinflammatory M1 macrophages rather than in BMC-derived anti-inflammatory M2 macrophages in vitro., Conclusions: Our data suggest that Mincle is induced in adipose tissue macrophages in obesity at least partly through the saturated fatty acid/TLR4/NF-κB pathway, thereby suggesting its pathophysiologic role in obesity-induced adipose tissue inflammation.
- Published
- 2011
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24. Enhanced inflammation in epicardial fat in patients with coronary artery disease.
- Author
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Hirata Y, Kurobe H, Akaike M, Chikugo F, Hori T, Bando Y, Nishio C, Higashida M, Nakaya Y, Kitagawa T, and Sata M
- Subjects
- Adipokines metabolism, Adipose Tissue metabolism, Aged, CD8-Positive T-Lymphocytes, Coronary Artery Disease metabolism, Female, Humans, Inflammation, Macrophages pathology, Male, Middle Aged, Pericardium metabolism, Subcutaneous Tissue metabolism, Subcutaneous Tissue pathology, Adipose Tissue pathology, Coronary Artery Disease pathology, Pericardium pathology
- Abstract
It has been hypothesized that epicardial fat, a local visceral fat depot with close proximity to coronary arteries, may serve as a source of inflammatory cytokines and cells in coronary atherosclerotic lesions. Here, we characterized infiltration of inflammatory cells and expression of adipocytokines in epicardial adipose tissue in patients with and without coronary artery disease (CAD). Pare samples were obtained from epicardial and subcutaneous adipose tissue during elective cardiac surgery (CAD, n = 8; non-CAD, n = 9). Inflammatory cell infiltration was investigated by immunohistochemical staining using antibodies against CD3, CD4, CD8 and CD68. Expression of adipocytokines was evaluated by real-time quantitative reverse transcription-polymerase chain reaction. Infiltration of macrophages and CD8-positive T cells in the epicardial adipose tissue in the CAD group was greater than that in the non-CAD group. In contrast, there was no significant difference between the two groups in the number of inflammatory cells in subcutaneous adipose tissue. No statistical difference could be found between the CAD group and the non-CAD group in the expression levels of adiponectin and inflammatory cytokines in epicardial adipose tissue. Our findings suggest that inflammatory cell infiltration is enhanced in epicardial adipose tissue, but not in subcutaneous fat, in patients with coronary artery disease. Chronic inflammation in epicardial fat may influence the pathogenesis of coronary atherosclerosis.
- Published
- 2011
- Full Text
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25. Endovascular injury induces rapid phenotypic changes in perivascular adipose tissue.
- Author
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Takaoka M, Suzuki H, Shioda S, Sekikawa K, Saito Y, Nagai R, and Sata M
- Subjects
- 3T3-L1 Cells, Adipokines metabolism, Adipose Tissue immunology, Angioplasty, Balloon adverse effects, Animals, Carotid Artery Injuries genetics, Carotid Artery Injuries immunology, Cell Proliferation, Chemokine CCL2 deficiency, Chemokine CCL2 genetics, Coculture Techniques, Culture Media, Conditioned metabolism, Disease Models, Animal, Hyperplasia, Inflammation Mediators metabolism, Interleukin-6 deficiency, Interleukin-6 genetics, Macrophages immunology, Macrophages pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle, Smooth, Vascular immunology, Muscle, Smooth, Vascular pathology, Myocytes, Smooth Muscle immunology, Myocytes, Smooth Muscle pathology, Phenotype, Rats, Rats, Wistar, Time Factors, Tumor Necrosis Factor-alpha deficiency, Tumor Necrosis Factor-alpha genetics, Adipose Tissue pathology, Carotid Artery Injuries pathology
- Abstract
Objective: Accumulating evidence suggests that adipose tissue not only stores energy but also secretes various bioactive substances called adipocytokines. Periadventitial fat is distributed ubiquitously around arteries throughout the body. It was reported that inflammatory changes in the periadventitial fat may have a direct role in the pathogenesis of vascular diseases accelerated by obesity. We investigated the effect of endovascular injury on the phenotype of perivascular fat., Methods and Results: Endovascular injury significantly upregulated proinflammatory adipocytokines and downregulated adiponectin within periadventitial fat tissue in models of mouse femoral artery wire injury and rat iliac artery balloon injury. Genetic disruption of tumor necrosis factor (TNF)-alpha attenuated upregulation of proinflammatory adipocytokine expression, with reduced neointimal hyperplasia after vascular injury. Local delivery of TNF-alpha to the periadventitial area enhanced inflammatory adipocytokine expression, which was associated with augmented neointimal hyperplasia in TNF-alpha-deficient mice. Conditioned medium from a coculture of 3T3-L1 and RAW264 cells stimulated vascular smooth muscle cell proliferation. An anti-TNF-alpha neutralizing antibody in the coculture abrogated the stimulating effect of the conditioned medium., Conclusions: Our findings indicate that endovascular injury induces rapid and marked changes in perivascular adipose tissue, mainly mediated by TNF-alpha. It is suggested that the phenotypic changes in perivascular adipose tissue may have a role in the pathogenesis of neointimal hyperplasia after angioplasty.
- Published
- 2010
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26. Periadventitial adipose tissue plays a critical role in vascular remodeling.
- Author
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Takaoka M, Nagata D, Kihara S, Shimomura I, Kimura Y, Tabata Y, Saito Y, Nagai R, and Sata M
- Subjects
- AMP-Activated Protein Kinases genetics, AMP-Activated Protein Kinases metabolism, Adiponectin administration & dosage, Adiponectin deficiency, Adiponectin genetics, Adiponectin metabolism, Adipose Tissue pathology, Adipose Tissue transplantation, Animals, Becaplermin, Cell Proliferation, Cells, Cultured, Connective Tissue pathology, Culture Media, Conditioned metabolism, Disease Models, Animal, Femoral Artery injuries, Femoral Artery pathology, Green Fluorescent Proteins genetics, Hyperplasia, Inflammation etiology, Inflammation pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Muscle, Smooth, Vascular metabolism, Obesity metabolism, Obesity pathology, Platelet-Derived Growth Factor metabolism, Proto-Oncogene Proteins c-sis, Rats, Recombinant Proteins metabolism, Tissue Culture Techniques, Transduction, Genetic, Tunica Intima metabolism, Tunica Intima pathology, Vascular Diseases etiology, Vascular Diseases pathology, Adipose Tissue metabolism, Connective Tissue metabolism, Femoral Artery metabolism, Inflammation metabolism, Obesity complications, Vascular Diseases metabolism
- Abstract
Rationale: Obesity is associated with a high incidence of cardiovascular complications. However, the molecular link between obesity and vascular disease is not fully understood. Most previous studies have focused on the association between cardiovascular disease and accumulation of visceral fat. Periadventitial fat is distributed ubiquitously around arteries throughout the body., Objective: Here, we investigated the impact of obesity on inflammation in the periadventitial adipose tissue and on lesion formation after vascular injury., Methods and Results: High-fat, high-sucrose feeding induced inflammatory changes and decreased adiponectin expression in the periadventitial adipose tissue, which was associated with enhanced neointima formation after endovascular injury. Removal of periadventitial fat markedly enhanced neointima formation after injury, which was attenuated by transplantation of subcutaneous adipose tissue from mice fed on regular chow. Adiponectin-deficient mice showed markedly enhanced lesion formation, which was reversed by local delivery, but not systemic administration, of recombinant adiponectin to the periadventitial area. The conditioned medium from subcutaneous fat attenuated increased cell number of smooth muscle cells in response to platelet derived growth factor-BB., Conclusions: Our findings suggest that periadventitial fat may protect against neointimal formation after angioplasty under physiological conditions and that inflammatory changes in the periadventitial fat may have a direct role in the pathogenesis of vascular disease accelerated by obesity.
- Published
- 2009
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27. Transplantation of adipose stromal cells, but not mature adipocytes, augments ischemia-induced angiogenesis.
- Author
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Sumi M, Sata M, Toya N, Yanaga K, Ohki T, and Nagai R
- Subjects
- Animals, Cell Differentiation, Green Fluorescent Proteins genetics, Ischemia physiopathology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Regional Blood Flow, Adipocytes transplantation, Adipose Tissue cytology, Ischemia therapy, Lower Extremity blood supply, Neovascularization, Physiologic, Stromal Cells transplantation
- Abstract
Therapeutic angiogenesis has emerged as a promising therapy to treat patients with ischemic diseases. Transplantation of bone marrow cells (BMCs) is reported to augment collateral development in ischemic organs either by differentiating into vascular cells or by secreting angiogenic cytokines. Recent evidence suggests that adipose tissues secrete a number of humoral factors and contain pluripotent stem cells. Here, we evaluated the therapeutic potential of adipose tissue-derived cells to promote angiogenesis in a mouse model of hind limb ischemia. Stromal vascular fraction cells (SVFs) were isolated from inguinal adipose tissue. Endothelial-like cells or smooth muscle-like cells could be obtained from the culture of SVFs in the presence of growth factors. Freshly isolated BMCs, SVFs, or mature adipocytes were transplanted into the ischemic hind limb of mice. SVFs significantly augmented collateral development as determined by the restoration of blood perfusion and capillary density of the ischemic muscle. Angiogenic effects of SVFs were as potent as those of BMCs. Mature adipocytes showed no proangiogenic effects. The ischemic muscle contained endothelial cells or smooth muscle cells that derived from the transplanted SVFs and BMCs. These results suggest that SVFs might be used to promote angiogenesis in ischemic tissues.
- Published
- 2007
- Full Text
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28. Resistance to neointimal hyperplasia and fatty streak formation in mice with adrenomedullin overexpression.
- Author
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Imai Y, Shindo T, Maemura K, Sata M, Saito Y, Kurihara Y, Akishita M, Osuga J, Ishibashi S, Tobe K, Morita H, Oh-hashi Y, Suzuki T, Maekawa H, Kangawa K, Minamino N, Yazaki Y, Nagai R, and Kurihara H
- Subjects
- Adrenomedullin, Animals, Apolipoproteins E metabolism, Calcitonin Gene-Related Peptide pharmacology, Femoral Artery metabolism, Femoral Artery pathology, Hydralazine pharmacology, Hyperplasia prevention & control, Mice, Mice, Knockout, Mice, Transgenic, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide metabolism, Peptide Fragments pharmacology, Tunica Intima drug effects, Tunica Intima metabolism, Adipose Tissue metabolism, Peptides metabolism, Tunica Intima pathology
- Abstract
Objective: Several in vitro studies have implicated that adrenomedullin (AM) plays an important role in the pathogenesis of vascular injury and fatty streak formation. To test this possibility in vivo, we evaluated 2 experimental models using transgenic mice overexpressing AM in a vessel-selective manner (AMTg mice)., Methods and Results: Placement of a periarterial cuff on femoral arteries resulted in neointimal formation at 2 to 4 weeks to a lesser extent in AMTg mice than in their wild-type littermates (at 28 days, intima/media area ratio 0.45+/-0.14 versus 1.31+/-0.41, respectively; P<0.001). This vasculoprotective effect observed in AMTg mice was inhibited by N(omega)-nitro-L-arginine methyl ester. We further examined the effect of AM on hypercholesterolemia-induced fatty streak formation by crossing AMTg mice with apolipoprotein E knockout mice (ApoEKO mice). The extent of the formation of fatty streak lesions was significantly less in ApoEKO/AMTg mice than in ApoEKO mice (percent lesion area 12.0+/-3.9% versus 15.8+/-2.8%, respectively; P<0.05). Moreover, endothelium-dependent vasodilatation as indicative of NO production was superior in AMTg/ApoEKO mice compared with ApoEKO mice., Conclusions: Taken together, our data demonstrated that AM possesses a vasculoprotective effect in vivo, which is at least partially mediated by NO.
- Published
- 2002
- Full Text
- View/download PDF
29. Adipose Tissue and Atherosclerosis
- Author
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Tanaka, Kimie and Sata, Masataka
- Subjects
Adipose tissue ,Adipocytokine ,Atherosclerosis - Abstract
Accumulating evidence revealed that adipose tissues secrete pro-inflammatory and anti-inflammatory humoral factors, called as adipocytokines. Most of the arteries are surrounded by perivascular adipose tissue (PVAT), which influences adjacent artery by secreting adipocytokines. PVATs are supposed to be athero-protective under healthy conditions, whereas PVATs are athero-promoting in obesity. Recent clinical studies suggested that coronary atherosclerosis is associated with increased volume of epicardial adipose tissue (EAT), PVAT of coronary artery. It was suggested that enhanced inflammation in EAT is also associated with vasospastic angina. In this review article, we will summarize recent findings about potential roles of EAT in the pathogenesis of coronary atherosclerosis.
- Published
- 2018
30. 肥満によって遊離する脂肪細胞由来のDNA断片が脂肪組織の炎症とインスリン抵抗性を引き起こす
- Author
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Nishimoto, Sachiko, Fukuda, Daiju, Higashikuni, Yasutomi, Tanaka, Kimie, Hirata, Yoichiro, Murata, Chie, Kim-Kaneyama, Joo-ri, Sato, Fukiko, Bando, Masahiro, Yagi, Shusuke, Soeki, Takeshi, Hayashi, Tetsuya, Imoto, Issei, Sakaue, Hiroshi, Shimabukuro, Michio, and Sata, Masataka
- Subjects
cell-free DNA ,肥満 ,インスリン抵抗性 ,Toll-like receptor ,inflammation ,insulin resistance ,慢性炎症 ,macrophage ,adipose tissue - Abstract
Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed increased release of cfDNA, as determined by the concentrations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in plasma. cfDNA released from degenerated adipocytes promoted monocyte chemoattractant protein-1 (MCP-1) expression in wild-type macrophages, but not in TLR9-deficient (Tlr9−/−) macrophages. Fat-fed Tlr9−/− mice demonstrated reduced macrophage accumulation and inflammation in adipose tissue and better insulin sensitivity compared with wild-type mice, whereas bone marrow reconstitution with wild-type bone marrow restored the attenuation of insulin resistance observed in fat-fed Tlr9−/− mice. Administration of a TLR9 inhibitory oligonucleotide to fat-fed wild-type mice reduced the accumulation of macrophages in adipose tissue and improved insulin resistance. Furthermore, in humans, plasma ssDNA level was significantly higher in patients with computed tomography–determined visceral obesity and was associated with homeostasis model assessment of insulin resistance (HOMA-IR), which is the index of insulin resistance. Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance.
- Published
- 2016
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