Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
24 巻 , 6 号
選択された号の論文の11件中1~11を表示しています
Review
  • Yasumi Uchida
    2017 年 24 巻 6 号 p. 539-551
    発行日: 2017/06/01
    公開日: 2017/06/01
    [早期公開] 公開日: 2017/04/04
    ジャーナル フリー

    Purpose of Review: In vivo imaging of the native substances, including lipoproteins, that comprise human atherosclerotic plaques is currently beyond the scope of any available imaging techniques. Color and near-infrared fluorescent angioscopy (CFA and NIRFA, respectively) systems have been recently developed for molecular imaging of lipoproteins within the human coronary arterial wall ex vivo and/or in vivo. The author reviews recent findings on lipoprotein deposition in human coronary plaques obtained by these imaging techniques.

    Recent Findings: Using specific biomarkers, native pro-atherogenic substances such as oxidized low-density lipoprotein (ox-LDL), LDL, triglycerides (TG), apolipoprotein B-100 (ApoB-100), and lysophosphatidylcholine (LPC), and the anti-atherogenic substance such as high-density lipoprotein (HDL) were visualized by CFA, and LDL and cholesterol by NIRFA, in coronary plaques obtained from autopsy subjects. The relationship between incidence and plaque morphology differed for each substance. The incidence of ox-LDL and LDL on color fluorescence microscopy correlated well with that observed using immunohistochemical techniques. During coronary catheterization in patients, ox-LDL, LDL, and HDL in coronary plaques were visualized by CFA or NIRFA.

    Conclusions: Using CFA or NIRFA, the distribution of the major native pro-atherogenic and anti-atherogenic lipoproteins and their components within human coronary plaques can be evaluated ex vivo and/or in vivo. Fluorescent angioscopy could help our understanding of the molecular mechanisms of coronary atherosclerosis and in the evaluation of the effects of therapy targeting the substances comprising atherosclerotic coronary plaques.

  • Sadao Takahashi
    2017 年 24 巻 6 号 p. 552-559
    発行日: 2017/06/01
    公開日: 2017/06/01
    [早期公開] 公開日: 2017/04/19
    ジャーナル フリー

    Very low-density lipoprotein (VLDL) receptor is a member of the low-density lipoprotein (LDL) receptor family. It binds triglyceride rich lipoprotein (TGRL) but not LDL, because it recognizes apolipoprotein (apo)E only but not apoB. The VLDL receptor functions as a peripheral lipoprotein receptor in concert with lipoprotein lipase (LPL) in heart, muscle, adipose tissue and macrophages. In contrast to the LDL receptor, VLDL receptor binds apo E2/2 VLDL and apoE3/3 VLDL particles, and its expression is not down-regulated by intracellular lipoproteins. It has been reported that both LDL-cholesterol (LDL-C) and postprandial triglyceride (chyromicron and VLDL remnants) are risk factors for human atherosclerotic cardiovascular disease (ASCVD). True ligands such as lipoprotein particles of the VLDL receptor are chyromicron remnant (CMR) and VLDL remnant (postprandial hyperlipidemia). Although the oxidized LDL (oxLDL)-scavenger receptors pathway is considered to be the main mechanism for macrophage foam cell formation, it seems that the TGRL-LPL-VLDL receptor pathway is also involved. Since Lp(a) is one of the ligands for the VLDL receptor, the Lp(a)-VLDL receptor pathway is another potential alternative. The expression of VLDL receptor protein in mouse macrophages is modest compared to that in rabbit and human macrophages, both in vitro and in vivo. Therefore, we need to elucidate the mechanism of human ASCVD not by using the mouse model and scavenger receptors pathway but instead using the rabbit model and VLDL receptor pathway, respectively.

  • Mashio Nakamura, Norikazu Yamada, Masaaki Ito
    2017 年 24 巻 6 号 p. 560-565
    発行日: 2017/06/01
    公開日: 2017/06/01
    [早期公開] 公開日: 2017/04/07
    ジャーナル フリー

    Direct oral anticoagulants (DOACs) were developed to compensate for the demerits of warfarin. In Japan, three factor Xa inhibitors are used for the treatment of venous thromboembolism (VTE): edoxaban, rivaroxaban, and apixaban. Despite problems, such as the inability to monitor their effect and the lack of an antidote, these inhibitors have the same efficacy as conventional treatment with warfarin, and they are associated with a significantly high degree of safety in relation to hemorrhagic complications. East Asians, including Japanese, suffer from hemorrhage more frequently; therefore, DOACs are considered to be highly effective. Although there is no evidence to date, DOACs may be effective in a wide variety of ways, including the possibility that they prevent recurrence over the long term, reduce the length of hospitalization, allow treatment to be started on an outpatient basis, and be effective in cancer patients.

Editorial
Original Article
  • Xin Guo, Yuanyuan Xiang, Heng Yang, Lijin Yu, Xiangdong Peng, Ren Guo
    2017 年 24 巻 6 号 p. 572-582
    発行日: 2017/06/01
    公開日: 2017/06/01
    [早期公開] 公開日: 2016/11/12
    ジャーナル フリー

    Aims: The interaction between lectin-like oxidized low density lipoprotein (LDL) receptor-1 (LOX-1) and oxidized LDL (ox-LDL) has been viewed as an important pathogenic factor for cardiovascular diseases. This study aimed to explore the association of a functional polymorphism rs1050283 in the 3′-untranslated region of the LOX-1 gene with atherosclerotic cerebral infarction (ACI) susceptibility, and we also investigated the effects of the rs1050283 polymorphism on LOX-1 expression and serum levels of sLOX-1 in patients with ACI.

    Methods: A case-controlled study was performed in 526 patients with ACI and 640 healthy controls. Genotyping was performed by DNA sequencing method. Real-time PCR and Western blotting were used to determine the level of LOX-1 expression. Serum levels of sLOX-1 were quantified using ELISA according to the manufacturer’s instruction.

    Results: The results of the present study showed that the frequency of rs1050283 T allele was significantly higher in patients with ACI than in healthy controls. We also found that the rs1050283 polymorphism T allele was associated with increased LOX-1 expression at mRNA and protein levels in patients with ACI. Furthermore, we also observed that among patients with ACI, those with the rs1050283 T allele showed an increased serum level of sLOX-1.

    Conclusion: Our research demonstrated that the rs1050283 T allele of LOX-1 is strongly associated with an increased risk for ACI in a Chinese population, which also affects levels of LOX-1 and sLOX-1.

  • Takashi Miida, Kunihiro Nishimura, Satoshi Hirayama, Yoshihiro Miyamot ...
    2017 年 24 巻 6 号 p. 583-599
    発行日: 2017/06/01
    公開日: 2017/06/01
    [早期公開] 公開日: 2017/03/17
    ジャーナル フリー

    Aim: Most epidemiological and clinical studies calculated low-density lipoprotein-cholesterol (LDL-C) by Friedewald's formula which cannot be used in the postprandial samples. Although the homogeneous assays with poor analytical performance were withdrawn from the market, it remained unclear whether the currently available reagents for LDL-C and high-density lipoprotein-cholesterol (HDL-C) are as accurate for postprandial samples as for fasting samples.

    Methods: Fresh blood samples were collected from 59 non-diseased and 109 diseased subjects. Postprandial samples constituted 72.9% and 39.4% of these samples. LDL-C and HDL-C concentrations were measured using the homogeneous assays of four manufacturers (Denka Seiken, Wako, Kyowa Medex, and Sekisui Medical). Simultaneously, LDL-C and HDL-C concentrations were determined using the reference measurement procedures (RMPs) of the Centers for Disease Control and Prevention (CDC). Total errors were calculated using a routine method (TEcom) and via error component analysis (TEECA).

    Results: All homogeneous assays for LDL-C and HDL-C met the National Cholesterol Education Program (NCEP) requirements in terms of coefficient of variation, and TEcom in both non-diseased and diseased subjects. LDL-C and HDL-C values measured by the homogeneous assays were in good agreement with those measured by the RMPs in both fasting and postprandial samples. The TEcom and TEECA values of the postprandial samples were similar to those of fasting samples, although the TEECA values were up to 4.4-fold greater than the TEcom values.

    Conclusions: In both non-diseased and diseased subjects, the homogeneous assays for LDL-C and HDL-C of four manufacturers are as accurate for postprandial samples as for fasting samples.

  • Setor K. Kunutsor, Francesco Zaccardi, Jouni Karppi, Sudhir Kurl, Jari ...
    2017 年 24 巻 6 号 p. 600-608
    発行日: 2017/06/01
    公開日: 2017/06/01
    [早期公開] 公開日: 2016/10/26
    ジャーナル フリー

    Aim: Low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c), which are components of total cholesterol, have each been suggested to be linked to the risk of sudden cardiac death (SCD). However, the relationship between LDL-c/HDL-c ratio and the risk of SCD has not been previously investigated. We aimed to assess the associations of LDL-c, HDL-c, and the ratio of LDL-c/HDL-c with the risk of SCD.

    Methods: Serum lipoprotein concentrations were assessed at baseline in the Finnish Kuopio Ischemic Heart Disease prospective cohort study of 2,616 men aged 42–61 years at recruitment. Hazard ratios (HRs) (95% confidence intervals [CI]) were assessed.

    Results: During a median follow-up of 23.0 years, a total of 228 SCDs occurred. There was no significant evidence of an association of LDL-c or HDL-c with the risk of SCD. In analyses adjusted for age, examination year, body mass index, systolic blood pressure, smoking, alcohol consumption, physical activity, years of education, diabetes, previous myocardial infarction, family history of coronary heart disease, and serum high sensitivity C-reactive protein, there was approximately a two-fold increase in the risk of SCD (HR 1.94, 95% CI 1.21–3.11; p=0.006), comparing the top (>4.22) versus bottom (≤2.30) quintile of serum LDL-c/HDL-c ratio.

    Conclusion: In this middle-aged male population, LDL-c or HDL-c was not associated with the risk of SCD. However, a high serum LDL-c/HDL-c ratio was found to be independently associated with an increased risk of SCD. Further research is warranted to understand the mechanistic pathways underlying this association.

  • Shuyu Zhou, Biyang Cai, Zhizhong Zhang, Yumeng Zhang, Li Wang, Keting ...
    2017 年 24 巻 6 号 p. 609-620
    発行日: 2017/06/01
    公開日: 2017/06/01
    [早期公開] 公開日: 2016/10/21
    ジャーナル フリー

    Aim: CDKN2A/2B near chromosome 9p21 has been proposed as a potential genetic etiology for both atherosclerosis and arterial calcification. DNA methylation, which can change the expression of CDKN2A/2B, may be an underlying mechanism for this association. This study aimed to evaluate whether CDKN2A/2B methylation is related to aortic arch calcification (AAC) in patients with ischemic stroke.

    Methods: DNA methylation levels of CDKN2A/2B was measured using venous blood samples in 322 patients with ischemic stroke. A total of 36 CpG sites around promoter regions of CDKN2A/2B were examined. AAC was quantified with Agatston score based on results of computed tomography angiography.

    Results: There were 248 (77.0%) patients with and 74 (23.0%) patients without evident AAC. Compared with patients without AAC, patients with AAC had higher methylation levels of CDKN2B (5.72 vs 4.94, P<0.001). Using a generalized linear model, positive correlation between methylation levels and log-transformed calcification scores was detected at CDKN2B (β=0.275±0.116, P= 0.018).

    Conclusion: Patients with higher levels of DNA methylation of CDKN2B may bear increased risk for AAC. Further studies to reveal the underlying mechanisms of this association are warranted for establishing a cause–effect relationship.

  • Tatsuya Shiraki, Osamu Iida, Mitsuyoshi Takahara, Yoshimitsu Soga, Shi ...
    2017 年 24 巻 6 号 p. 621-629
    発行日: 2017/06/01
    公開日: 2017/06/01
    [早期公開] 公開日: 2016/10/13
    ジャーナル フリー

    Aim: The treatment strategy for hemodialysis (HD) patients with critical limb ischemia (CLI) has been clinically debatable. Here we compared clinical outcomes after bypass surgery (BSX) and after endovascular therapy (EVT) using propensity score matching.

    Methods: A retrospective multicenter database of 246 (68 BSX and 178 EVT) consecutive HD patients with CLI (79% with tissue loss) who underwent infrainguinal revascularization from 2007 to 2009 was used to compare clinical outcomes, including overall survival (OS), major amputation (MA), major adverse limb event (MALE: repeat EVT, surgical reconstruction, or MA), and MALE-free survival after BSX vs. EVT using propensity score matching.

    Results: The median (interquartile range) follow-up duration after revascularization was 21 (8–33) months. The analysis of the 63 propensity score-matched pairs revealed no significant difference in OS (53% vs. 52%, P=0.96), MA (25% vs. 14%, P=0.71), MALE (42% vs. 58%, P=0.63), and MALE-free survival (33% vs. 11%, P=0.37) at 3 year after BSX vs. EVT.

    Conclusions: In HD patients with CLI who underwent infrainguinal revascularization, OS, MA, MALE, and MALE-free survival rates were not significantly different after EVT vs. BSX. The less invasive EVT should be considered as the first-choice therapeutic strategy for HD patients with CLI.

  • Kumiko Momoki, Hiroshi Kataoka, Takahito Moriyama, Toshio Mochizuki, K ...
    2017 年 24 巻 6 号 p. 630-642
    発行日: 2017/06/01
    公開日: 2017/06/01
    [早期公開] 公開日: 2016/10/26
    ジャーナル フリー

    Aim: The influence of serum urate on kidney disease is attracting attention, but the effects of uric acid (UA) on nephrosclerosis have not been elucidated.

    Methods: We reviewed data from 45 patients diagnosed with arterial/arteriolar nephrosclerosis. The renal outcomes of the arterial/arteriolar nephrosclerosis patients were assessed by performing logistic and Cox regression analyses. A Kaplan–Meier analysis was used to evaluate the impact of hyperuricemia (HU) on kidney survival. The renal outcomes of patients with and without HU were compared by using a propensity score-matched cohort.

    Results: The logistic regression models showed no significant differences in renal outcomes, according to baseline parameters or follow-up parameters, except the serum UA value and body mass index (BMI). Baseline serum UA level had the highest odds ratio (OR) for estimated glomerular filtration rate (eGFR) decline (OR, 1.86; 95% confidence interval (CI), 1.12 to 3.45), among the parameters assessed. In the multivariate Cox regression analysis, HU (UA ≥8.0 mg/dL) (P=0.01) and BMI (P=0.03) were significantly associated with a ≥50% eGFR decline or ESRD. The Kaplan–Meier analysis in the propensity score-matched cohort indicated that the renal survival rate of the group of arterial/arteriolar nephrosclerosis patients with HU was significantly lower than that of the group without HU (log rank, P=0.03).

    Conclusion: The results of this study suggest that the baseline serum UA value can serve as a renal outcome predictor in arterial/arteriolar nephrosclerosis patients.

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