Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Volume 24, Issue 11
Displaying 1-12 of 12 articles from this issue
Original Article
  • Takeo Ichii, Ryota Morimoto, Takahiro Okumura, Hideki Ishii, Yosuke Ta ...
    2017 Volume 24 Issue 11 Pages 1092-1104
    Published: November 01, 2017
    Released on J-STAGE: November 01, 2017
    Advance online publication: April 08, 2017

    Aim: Fast-progressing vascular calcification (VC) is accompanied by renal atrophy and functional deterioration along with atherosclerosis in patients with chronic kidney disease (CKD). However, the relationship between VC progression and renal functional and/or morphological changes remains unclear.

    Methods: We included 70 asymptomatic patients with CKD without hemodialysis in our study. To identify temporal variations, the coronary artery calcification score (CACS), abdominal aortic calcification index (ACI), and renal parenchymal volume index (RPVI) were determined via spiral computed tomography scans taken during the study. We investigated significant factors related to annualized variations of CACS (ΔCACS/y) and ACI (ΔACI/y).

    Results: During the follow-up period (4.6 years), median values of CACS [in Agatston units (AU)] and ACI increased from 40.2 to 113.3 AU (p=0.053) and from 13.2 to 21.7% (p=0.036), respectively. Multivariate analysis revealed that CACS at baseline (p<0.001) and diabetes mellitus (DM) status (p=0.037) for ΔCACS/y and ACI at baseline (p=0.017) and hypertension (HT) status (p= 0.046) for ΔACI/y were significant independent predictors. Furthermore, annualized RPVI variation was significantly related to both ΔCACS/y and ΔACI/y (R=−0.565, p<0.001, and R=−0.289, p=0.015, respectively). On the other hand, independent contributions of the estimated glomerular filtration rate (eGFR) and annualized eGFR variation to VC progression were not confirmed.

    Conclusion: The degree of VC at baseline, DM, HT, and changes in renal volume, but not eGFR, had a strong impact on VC progression in patients with CKD.

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  • Mikio Takanashi, Yoshino Taira, Sachiko Okazaki, Satoru Takase, Takesh ...
    2017 Volume 24 Issue 11 Pages 1105-1116
    Published: November 01, 2017
    Released on J-STAGE: November 01, 2017
    Advance online publication: April 12, 2017

    Aim: Myriad biological effects of leptin may lead to broad therapeutic applications for various metabolic diseases, including diabetes and its complications; however, in contrast to its anorexic effect, the molecular mechanisms underlying adipopenic and glucose-lowering effects of leptin have not been fully understood. Here we aim to clarify the role of hormone-sensitive lipase (HSL) in leptin's action.

    Methods: Wild-type (WT) and HSL-deficient (HSLKO) mice were made hyperleptinemic by two commonly-used methods: adenovirus-mediated overexpression of leptin and continuous subcutaneous infusion of leptin by osmotic pumps. The amount of food intake, body weights, organ weights, and parameters of glucose and lipid metabolism were measured.

    Results: Hyperleptinemia equally suppressed the food intake in WT and HSLKO mice. On the other hand, leptin-mediated fat loss and glucose-lowering were significantly blunted in the absence of HSL when leptin was overexpressed by recombinant adenovirus carrying leptin. By osmotic pumps, the fat-losing and glucose-lowering effects of leptin were milder due to lower levels of hyperleptinemia; although the difference between WT and HSLKO mice did not reach statistical significance, HSLKO mice had a tendency to retain more fat than WT mice in the face of hyperleptinemia.

    Conclusions: We clarify for the first time the role of HSL in leptin's effect using a genetic model: leptin-promoted fat loss and glucose-lowering are at least in part mediated via HSL-mediated lipolysis. Further studies to define the pathophysiological role of adipocyte lipases in leptin action may lead to a new therapeutic approach to circumvent leptin resistance.

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  • Jinkee Park, Yoochan Kwon, Hyuntea Park
    2017 Volume 24 Issue 11 Pages 1117-1124
    Published: November 01, 2017
    Released on J-STAGE: November 01, 2017
    Advance online publication: July 01, 2017

    Aim: Sarcopenic obesity (SO) is closely associated with cardiovascular disease (CVD) in elderly women. Increases in body fat and decreases in muscle mass are closely associated with increased carotid intima-media thickness (CIMT). The aim of this study was to examine the influence of a 24-week aerobic and resistance training program on carotid parameters in SO.

    Methods: Fifty elderly women (74.1±6.1 years) with SO were randomly divided into an exercise group and a control group. The exercise group performed combined exercise over 24 weeks, consisting of resistance and aerobic training for 50-80 min, 5 times a week. Carotid variables were measured using B-mode ultrasound. The differences in the carotid variables and the relative changes between baseline and after 24 weeks were evaluated.

    Results: In the analysis of variance (ANOVA) results, CIMT (p=0.013), systolic flow velocity (p=0.007), diastolic flow velocity (p=0.006), and wall shear rate (p=0.010) showed significant interactions. In paired t-test results of the exercise group, CIMT significantly decreased (p<0.01) and systolic flow velocity (p<0.01), diastolic flow velocity (p<0.001), and wall shear rate (p<0.05) significantly increased after 24 weeks.

    Conclusion: The 24-week combined exercise effectively decreased CIMT and increased carotid flow velocity and wall shear ratio. Therefore, combined exercise is thought to contribute to the improvement of the risk of CVD in elderly women with SO.

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  • Satoru Suwa, Manabu Ogita, Katsumi Miyauchi, Taketo Sonoda, Hirokazu K ...
    2017 Volume 24 Issue 11 Pages 1125-1131
    Published: November 01, 2017
    Released on J-STAGE: November 01, 2017
    Advance online publication: March 17, 2017

    Aims: Cardiovascular risk persists despite intensive lipid lowering therapy using statins. Serum levels of lipoprotein (a) [Lp(a)] can be a residual cardiovascular risk for adverse events. Aim of the present study was to evaluate the impact of Lp(a) on long-term clinical outcomes in patients treated with statin after percutaneous coronary intervention.

    Methods: We prospectively enrolled 3507 consecutive CAD patients who underwent a first percutaneous coronary intervention (PCI) between 1997 and 2011 at our institution. We identified 1768 patients (50.4%) who had treated with statin during PCI. Eligible 1336 patients were stratified to two groups according to Lp(a) levels (median Lp (a) 21.5 mg/dL). The primary outcome was major adverse cardiac events (MACE) including cardiac death and non-fatal acute coronary syndrome.

    Results: MACE occurred 144 (10.8%) including 34 (2.5%) cardiac death and 110 (8.7%) non-fatal ACS during median follow-up period of 1920 days. The cumulative rate of MACE was significantly higher in group with high Lp(a) group (log-rank p=0.0460). Multivariate Cox regression analysis showed a significant correlation between Lp (a) levels treated as a natural logarithm-transformed continuous variable and increased MACE (adjusted HR for MACE 1.28, 95%CI 1.04-1.58, p=0.0184)

    Conclusion: Elevated levels of Lp(a) is significantly associated with long-term adverse clinical outcomes among CAD patients who received statin therapy after PCI.

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  • Maki Tsujita, Mohammad Anwar Hossain, Rui Lu, Tomoe Tsuboi, Kuniko Oku ...
    2017 Volume 24 Issue 11 Pages 1132-1149
    Published: November 01, 2017
    Released on J-STAGE: November 01, 2017
    Advance online publication: April 19, 2017

    Aim: To study atherosclerosis risk in diabetes, we investigated ATP-binding cassette transporter A1 (ABCA1) expression and high-density lipoprotein (HDL) biogenesis in the liver and hepatocytes under hyperglycemic conditions.

    Methods and Results: In streptozotocin-induced diabetic mice, plasma HDL decreased while ABCA1 protein increased without changing its mRNA in the liver, only in the animals that responded to the treatment to show hypoinsulinemia and fasting hyperglycemia but not in the poor responders not showing those. To study the mechanism for this finding, hepatocytes were isolated from the control and diabetic mice, and they showed no difference in expression of ABCA1 protein, its mRNA, and HDL biogenesis in 1 g/l d-glucose but showed decreased HDL biogenesis in 4.5 g/l d-glucose although ABCA1 protein increased without change in its mRNA. Similar findings were confirmed in HepG2 cells with d-glucose but not with l-glucose. Thus, these cell models reproduced the in vivo findings in hyperglycemia. Labeling of cell surface protein revealed that surface ABCA1 decreased in high concentration of d-glucose in HepG2 cells despite the increase of cellular ABCA1 while not with l-glucose. Immunostaining of ABCA1 in HepG2 cells demonstrated the decrease of surface ABCA1 but increase of intracellular ABCA1 with high d-glucose. Clearance of ABCA1 was retarded both in primary hepatocytes and HepG2 cells exposed to high d-glucose but not to l-glucose, being consistent with the decrease of surface ABCA1.

    Conclusions: It is suggested that localization of ABCA1 to the cell surface is decreased in hepatocytes in hyperglycemic condition to cause decrease of HDL biogenesis.

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  • Sohsuke Yamada, Hiroaki Kawaguchi, Tomonobu Yamada, Xin Guo, Kei Matsu ...
    2017 Volume 24 Issue 11 Pages 1150-1166
    Published: November 01, 2017
    Released on J-STAGE: November 01, 2017
    Advance online publication: May 11, 2017

    Aim: We have recently established a novel swine model for studies of atherosclerosis using MicrominipigsTM (µMPs) fed a high-fat/high-cholesterol diet (HcD). Using this swine model, we re-evaluated the effects of dietary cholic acid (CA) on serum lipid profile, atherosclerosis and hepatic injuries.

    Methods: The µMPs were fed HcD supplemented with 0.7% CA (HcD+CA) for eight weeks, and the effect of CA on serum lipoprotein levels, expression of oxidative stress markers, adiposity and lesion formation in the aorta, liver, and other organs was investigated.

    Results: The HcD+CA-fed group exhibited more visceral adiposity, progression of atherosclerosis and higher serum levels of oxidative stress markers than the HcD-fed group, even though they showed similar serum lipid levels. The liver demonstrated increased lipid accumulation, higher expression of oxidative stress markers, accelerated activation of foamy Kupffer cells and stellate cells, and increased hepatocyte apoptosis, indicating non-alcoholic fatty liver disease (NAFLD). Intriguingly, foamy macrophage mobilization was observed in various organs, including the reticuloendothelial system, pulmonary capillary vessels and skin very often in HcD+CA-fed µMPs.

    Conclusion: To our knowledge, this is the first large animal model, in which visceral obesity, NAFLD and atherosclerosis are concomitantly induced by dietary manipulation. These data suggest the detrimental effects of CA, potentially through local and systemic activation of oxidative stress-induced signaling to macrophage mobilization, on the acceleration of visceral adiposity, atherosclerosis and NAFLD.

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  • Hayato Matsushima, Naohisa Hosomi, Naoyuki Hara, Takeshi Yoshimoto, Sh ...
    2017 Volume 24 Issue 11 Pages 1167-1173
    Published: November 01, 2017
    Released on J-STAGE: November 01, 2017
    Advance online publication: May 15, 2017

    Aim: Both the ankle brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are surrogates for atherosclerosis. In this study, we aimed to evaluate the ability of ABI and baPWV to predict stroke outcome in patients with first-ever non-cardioembolic stroke.

    Methods: This study included consecutive patients with first-ever non-cardioembolic stroke admitted within 1 week after onset to Ota Memorial Hospital between January 2011 and December 2013. Baseline characteristics and National Institutes of Health stroke scale scores at admission were noted. ABI and baPWV were evaluated within 5 days of admission. The patients were categorized according to ABI (cut-off 0.9) and baPWV (cut-off 1870 cm/s) determined using the receiver operation curve for poor outcome. Clinical outcomes were defined based on the modified Rankin scale (mRS) scores 3 months after stroke onset as good (0 and 1) or poor (2–6).

    Results: A total of 861 patients were available for evaluation. ABI <0.9 and baPWV >1870 cm/s were associated with poor outcome in the univariate analysis (p<0.001 and p<0.001, respectively). After adjusting for factors that showed differences between groups, ABI <0.9 was associated with poor outcome. Among patients with ABI ≥ 0.9, higher baPWV showed a slight association with poor outcome after adjustment [odds ratio 1.46 (95% CI 0.95–2.27)].

    Conclusion: Our study suggests that the stroke outcome can be predicted using ABI and to an extent using baPWV when ABI ≥ 0.9 in patients with non-cardioembolic stroke.

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  • Kazuhisa Takamura, Shinichiro Fujimoto, Takeshi Kondo, Makoto Hiki, Yu ...
    2017 Volume 24 Issue 11 Pages 1174-1185
    Published: November 01, 2017
    Released on J-STAGE: November 01, 2017
    Advance online publication: July 01, 2017

    Aim: Coronary computed tomography angiography (CCTA) findings of positive remodeling (index >1.1) and low-attenuation plaque (<30 Hounsfield units) are recognized as CT-verified high-risk plaque (CT-HRP). Therefore, we investigated the incremental prognostic value of evaluation of plaque characteristics using CCTA in asymptomatic patients.

    Methods: Overall, 495 consecutive patients without any known coronary artery disease who underwent CCTA were included in this study. Patients who underwent revascularization within 30 days of CCTA or had scans with poor image quality were excluded. Clinical follow-up data (716.5±262.6 days) were available for 339 patients, who were analyzed for the current study. Framingham risk score (FRS), coronary artery calcium score (CACS), and CT-HRP were investigated as predictors of cardiac events by multivariable analysis using Cox proportional hazard model. Improvement of predictive accuracy by including CT findings was evaluated from reclassification [net reclassification indices (NRI) and integrated discrimination improvement (IDI)] standpoints.

    Results: During the follow-up period, 9 cardiac events (cardiac death: 0, nonfatal myocardial infarction: 2, hospitalization for unstable or progressive angina: 7) occurred. Multivariate Cox proportional hazard analysis demonstrated that CACS (HR, 13.23; 95% CI, 1.62–107.78, p<0.0164) and CT-HRP (HR, 11.27; 95% CI, 1.24–102.12, p<0.0321) were the independent predictors of cardiac events. NRI was 0.9556 (p<0.0007) and IDI was 0.2582 (p<0.0203), and the diagnostic performance improved by CT-HRP added to the combination of CACS and FRS.

    Conclusion: Although the cardiac event rate was low, the evaluation of CCTA plaque characteristics may provide incremental prognostic value to CACS in asymptomatic patients.

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  • Tomonori Sugiura, Yasuaki Dohi, Hiroyuki Takase, Sumiyo Yamashita, Sat ...
    2017 Volume 24 Issue 11 Pages 1186-1198
    Published: November 01, 2017
    Released on J-STAGE: November 01, 2017
    Advance online publication: July 01, 2017

    Aim: Cigarette smoking is one of the major risk factors for cardiovascular diseases and induces deleterious vascular damage. Oxidative stress is involved in vascular inflammation, the process of atherosclerosis. The purpose of the present study was to investigate whether the effects of oxidative stress on the arterial wall differ between smokers and non-smokers.

    Methods: Male smokers and non-smokers without physical deconditioning who visited Enshu hospital for an annual physical check-up were enrolled in the study. To assess oxidative stress, serum levels of derivative reactive oxygen metabolites (d-ROM) were measured. The radial augmentation index (RAI) was measured using an automated device and was used as an index for arterial stiffness.

    Results: Univariate and multivariate linear regression analysis showed that RAI was independently associated with d-ROM levels only in smokers. Moreover, RAI was significantly higher in smokers than in non-smokers. Logistic regression analysis with the endpoint of a higher RAI than the mean revealed that older age (>65 years), hypertension, and smoking were independently associated with higher RAI. Similarly, logistic regression analysis with the endpoint of higher d-ROM levels than the mean showed that older age and smoking were independently associated with higher d-ROM levels.

    Conclusions: Increased RAI is significantly associated with smoking and, in smokers, with increased d-ROM levels. These results suggest that the effects of oxidative stress on arterial properties differ between smokers and non-smokers and that oxidative stress is closely associated with arterial stiffness, especially in smokers.

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