Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
25 巻 , 3 号
  • Shuichiro Kaji
    2018 年 25 巻 3 号 p. 203-212
    発行日: 2018/03/01
    公開日: 2018/03/01
    [早期公開] 公開日: 2017/11/10
    ジャーナル フリー

    Stanford type B aortic dissection (TBAD) is a life-threatening disease. Current therapeutic guidelines recommend medical therapy with aggressive blood pressure lowering for patients with acute TBAD unless they have fatal complications. Although patients with uncomplicated TBAD have relatively low early mortality, aorta-related adverse events during the chronic phase worsen the long-term clinical outcome. Recent advances in thoracic endovascular aortic repair (TEVAR) can improve clinical outcomes in patients with both complicated and uncomplicated TBAD. According to present guidelines, complicated TBAD patients are recommended for TEVAR. However, the indication in uncomplicated TBAD remains controversial. Recent results of randomized trials, which compared the clinical outcome in patients treated with optimal medical therapy and those treated with TEVAR, suggest that preemptive TEVAR should be considered in uncomplicated TBAD with suitable aortic anatomy. However, these trials failed to show improvement in early mortality in patients treated with TEVAR compared with patients treated with optimal medical therapy, which suggest the importance of patient selection for TEVAR. Several clinical and imaging-related risk factors have been shown to be associated with early disease progression. Preemptive TEVAR might be beneficial and should be considered for high-risk patients with uncomplicated TBAD. However, an interdisciplinary consensus has not been established for the definition of patients at high-risk of TBAD, and it should be confirmed by experts including physicians, radiologists, interventionalists, and vascular surgeons. This review summarizes the current understanding of the therapeutic strategy in patients with TBAD based on evidence and expert consensus.

  • Jianglin Fan, Yajie Chen, Haizhao Yan, Manabu Niimi, Yanli Wang, Jingy ...
    2018 年 25 巻 3 号 p. 213-220
    発行日: 2018/03/01
    公開日: 2018/03/01
    [早期公開] 公開日: 2017/10/19
    ジャーナル フリー

    Rabbits are one of the most used experimental animals for biomedical research, particularly as a bioreactor for the production of antibodies. However, many unique features of the rabbit have also made it as an excellent species for examining a number of aspects of human diseases such as atherosclerosis. Rabbits are phylogenetically closer to humans than rodents, in addition to their relatively proper size, tame disposition, and ease of use and maintenance in the laboratory facility. Due to their short life spans, short gestation periods, high numbers of progeny, low cost (compared with other large animals) and availability of genomics and proteomics, rabbits usually serve to bridge the gap between smaller rodents (mice and rats) and larger animals, such as dogs, pigs and monkeys, and play an important role in many translational research activities such as pre-clinical testing of drugs and diagnostic methods for patients. The principle of using rabbits rather than other animals as an experimental model is very simple: rabbits should be used for research, such as translational research, that is difficult to accomplish with other species. Recently, rabbit genome sequencing and transcriptomic profiling of atherosclerosis have been successfully completed, which has paved a new way for researchers to use this model in the future. In this review, we provide an overview of the recent progress using rabbits with specific reference to their usefulness for studying human atherosclerosis.

Original Article
  • Akihiro Tokushige, Masaaki Miyata, Takeshi Sonoda, Ippei Kosedo, Daisu ...
    2018 年 25 巻 3 号 p. 224-232
    発行日: 2018/03/01
    公開日: 2018/03/01
    [早期公開] 公開日: 2017/08/30
    ジャーナル フリー

    Aim: Previous studies have reported a 10.2%–22% rate of silent cerebral infarction and a 0.1%–1% rate of symptomatic cerebral infarction after coronary angiography (CAG). However, the risk factors of cerebral infarction after CAG have not been fully elucidated. For this reason, we investigated the incidence and risk factors of CVD complications within 48 h after CAG using magnetic resonance imaging (MRI) (Diffusion-weighted MRI) at Kagoshima University Hospital.

    Methods: From September 2013 to April 2015, we examined the incidence and risk factors, including procedural data and patients characteristics, of cerebrovascular disease after CAG in consecutive 61 patients who underwent CAG and MRI in our hospital.

    Results: Silent cerebral infarction after CAG was observed in 6 cases (9.8%), and they should not show any neurological symptoms of cerebral infarction. Only prior coronary artery bypass grafting (CABG) was more frequently found in the stroke group (n=6) than that in the non-stroke group (n=55); however, no significant difference was observed (P=0.07). After adjusting for confounders, prior CABG was a significant independent risk factor for the incidence of stroke after CAG (odds ratio: 11.7, 95% confidence interval: 1.14–129.8, P=0.04).

    Conclusions: We suggested that the incidence of cerebral infarction after CAG was not related to the catheterization procedure per se but may be caused by atherosclerosis with CABG.

  • Takehiro Hashikata, Taiki Tojo, Yusuke Muramatsu, Toshimitsu Sato, Ryo ...
    2018 年 25 巻 3 号 p. 233-243
    発行日: 2018/03/01
    公開日: 2018/03/01
    [早期公開] 公開日: 2017/08/19
    ジャーナル フリー

    Aim: Fractional flow reserve (FFR) reflects on the diffuse atherosclerosis per coronary artery. It is unknown whether the statin therapy affects long term FFR after stenting. The aim of this study was to evaluate the long term FFR after stent implantation in patients who are intaking fixed-dose rosuvastatin.

    Methods: A total of 22 patients with stable angina pectoris were enrolled. The values of FFR were measured before, immediately after, and 18 months after (follow-up day) the implantation of everolimus eluting stent (EES; Promus ElementTM or Promus Element PlusTM). A fixed dose of rosuvastatin at 5 mg/day was administrated to all patients.

    Results: Of the 22 patients, 2 were excluded because of adverse effect of rosuvastatin and in-stent total occlusion after EES implantation. Overall, the values of FFR immediately after and 18 months after EES implantation did not show significant change (from 0.90±0.05 to 0.88±0.06, p=0.16). However, there was a significant negative correlation between low density lipoprotein (LDL) cholesterol level at follow-up day and changes in the value of FFR (p=0.01, r =-0.74). There was an increase in the FFR value after stenting in 8 out of 9 patients with LDL cholesterol level below 75 mg/dl (area under the curve 0.92, p=0.0005).

    Conclusions: LDL cholesterol level was associated with the change in the FFR value in patients following stent implantation. Lower LDL cholesterol tended to improve in the long-term FFR, underscoring the importance of lowering LDL cholesterol to prevent the progression of coronary atherosclerosis.

  • Qiong Ye, Guo-Ping Tian, Hai-Peng Cheng, Xin Zhang, Xiang Ou, Xiao-Hua ...
    2018 年 25 巻 3 号 p. 244-253
    発行日: 2018/03/01
    公開日: 2018/03/01
    [早期公開] 公開日: 2017/09/01
    ジャーナル フリー

    Aims: Atherosclerosis is the most common cause of cardiovascular disease, such as myocardial infarction and stroke. Previous study revealed that microRNA (miR)-134 promotes lipid accumulation and proinflammatory cytokine secretion through angiopoietin-like 4 (ANGPTL4)/lipid lipoprotein (LPL) signaling in THP-1 macrophages.

    Methods: ApoE KO male mice on a C57BL/6 background were fed a high-fat/high-cholesterol Western diet, from 8 to 16 weeks of age. Mice were divided into four groups, and received a tail vein injection of miR-134 agomir, miR-134 antagomir, or one of the corresponding controls, respectively, once every 2 weeks after starting the Western diet. After 8 weeks we measured aortic atherosclerosis, LPL Activity, mRNA and protein levels of ANGPTL4 and LPL, LPL/ low-density lipoprotein receptor related protein 1 Complex Formation, proinflammatory cytokine secretion and lipid levels.

    Results: Despite this finding, the influence of miR-134 on atherosclerosis in vivo remains to be determined. Using the well-characterized mouse atherosclerosis model of apolipoprotein E knockout, we found that systemic delivery of miR-134 agomir markedly enhanced the atherosclerotic lesion size, together with a significant increase in proinflammatory cytokine secretion and peritoneal macrophages lipid contents. Moreover, overexpression of miR-134 decreased ANGPTL4 expression but increased LPL expression and activity in both aortic tissues and peritoneal macrophages, which was accompanied by increased formation of LPL/low-density lipoprotein receptor-related protein 1 complexes in peritoneal macrophages. However, an opposite effect was observed in response to miR-134 antagomir.

    Conclusions: These findings suggest that miR-134 accelerates atherogenesis by promoting lipid accumulation and proinflammatory cytokine secretion via the ANGPTL4/LPL pathway. Therefore, targeting miR-134 may offer a promising strategy for the prevention and treatment of atherosclerotic cardiovascular disease.

  • Huan Liu, Jinbo Liu, Hongwei Zhao, Yingyan Zhou, Lihong Li, Hongyu Wan ...
    2018 年 25 巻 3 号 p. 254-261
    発行日: 2018/03/01
    公開日: 2018/03/01
    [早期公開] 公開日: 2017/09/12
    ジャーナル フリー

    Aim: The study was done to establish the relationship between serum uric acid (UA) and vascular function and structure parameters including carotid femoral pulse wave velocity (CF-PWV), carotid radial pulse wave velocity (CR-PWV), cardio ankle vascular index (CAVI), ankle brachial index (ABI), and carotid intima-media thickness (CIMT), and the gender difference in a real-world population from China.

    Methods: A total of 979 subjects were enrolled (aged 60.86±11.03 years, male 416 and female 563). Value of UA was divided by 100 (UA/100) for analysis.

    Results: Body mass index (BMI), diastolic blood pressure (DBP), fasting plasma glucose (FPG), UA, and UA/100 were significantly higher in males compared with females (all p<0.05); pulse pressure (PP), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were lower in males than females (all p<0.05). All vascular parameters including CF-PWV, CR-PWV, CAVI, ABI, and CIMT were higher in males than females (all p<0.05). Multiple linear regression analysis showed that UA/100 was independently positively linearly correlated with CAVI (B=0.143, p=0.001) and negatively correlated with ABI in the male population (B=-0.012, p=0.020). In people with higher UA, the risk of higher CF-PWV was 1.593 (p<0.05).

    Conclusions: 1. All vascular parameters were higher in males than females. There was no gender difference in the relationship between UA and vascular markers except in ABI. 2. UA was independently linearly correlated with CAVI. 3. In people with higher UA level, the risk of higher CF-PWV increased. Therefore, higher UA may influence the vascular function mainly instead of vascular structure.

  • Naohisa Hosomi, Yoji Nagai, Kazuo Kitagawa, Yoko Nakagawa, Shiro Aoki, ...
    2018 年 25 巻 3 号 p. 262-268
    発行日: 2018/03/01
    公開日: 2018/03/01
    [早期公開] 公開日: 2017/09/16
    ジャーナル フリー

    Aims: The J-STARS study examined whether pravastatin (10 mg/day) reduces recurrence of stroke in non-cardioembolic ischemic stroke patients who were enrolled within 1 month to 3 years after initial stroke events (, NCT00221104). The main results showed that the frequency of atherothrombotic stroke was low in pravastatin-treated patients, although no effect of pravastatin was found for the other stroke subtypes. We evaluated differences of early (within 6 months) or late (after 6 months) pravastatin treatment benefits on the incidence of stroke or transient ischemic attack (TIA), as well as atherothrombotic stroke and the other subtypes.

    Methods: Subjects in the J-STARS study were classified into two cohorts, depending on whether they enrolled early (1 to 6 months) or late (6 months to 3 years) following initial stroke events.

    Results: A total of 1578 patients (491 female, 66.2±8.5 years) were randomly assigned to either the pravastatin group (n=793; n=426 in the early cohort, n=367 in the late cohort) or the control group (n=785; n=417 in the early cohort, n=368 in the late cohort). During the follow-up of 4.9± 1.4 years, the rate of atherothrombotic stroke was lower in the pravastatin group compared to controls in the early cohort (0.24 vs. 0.88%/year, p=0.01) but not in the late cohort (0.17 vs. 0.39%/year, p=0.29). However, this difference of pravastatin effect on atherothrombotic stroke was not significantly interacted by the early or late cohort (p=0.59). The incidence rates of other stroke subtype were not different in between pravastatin and control groups despite the timing of entry.

    Conclusions: Pravastatin is likely to reduce atherothrombotic stroke in patients enrolled within 6 months after stroke onset. However, the clinical efficacy for prevention of recurrent stroke was not conclusive with earlier statin treatment.

  • Toshiro Kitagawa, Hideya Yamamoto, Takuya Hattori, Kazuhiro Sentani, S ...
    2018 年 25 巻 3 号 p. 269-280
    発行日: 2018/03/01
    公開日: 2018/03/01
    [早期公開] 公開日: 2017/09/20
    ジャーナル フリー

    Aims: Tumor necrosis factor (TNF)-α reportedly has key pro-inflammatory properties in both atherosclerosis and adipocytes. To further investigate the biologic impact of epicardial adipose tissue (EAT) on coronary atherosclerosis, we evaluated the relationship between TNF-α gene expression in EAT and clinically-assessed coronary atherosclerosis on computed tomography (CT).

    Methods: We studied 47 patients before cardiac surgery (coronary artery bypass grafting [CABG], n=26; non-CABG, n=21), assessing visceral adipose tissue (VAT) area, EAT volume, coronary calcium score (CCS), and the presence of non- and/or partially-calcified coronary plaque (NCP) on CT angiography. EAT and subcutaneous adipose tissue (SAT) samples were obtained during cardiac surgery. TNF-α mRNA in EAT was measured using quantitative real-time PCR, and normalized to that of SAT as control adipose tissue.

    Results: There was no difference in the TNF-α expression level between patients scheduled for CABG and non-CABG surgery (p=0.23), or among the subgroups based on CCS (p=0.68), while patients with NCP had the higher TNF-α expression level than those without NCP (median [interquartile range], 2.50 [1.01–5.53] versus. 1.03 [0.64–2.16], p=0.022). On multivariate analysis adjusted for age, sex, coronary risk factors, statin therapy, CABG versus non-CABG, VAT area, and EAT volume, the presence of NCP had close correlation with the elevated TNF-α expression level (β=0.79, p=0.003).

    Conclusions: TNF-α expressed regionally in EAT may exert potent effects on the progression of coronary atherosclerosis, suggesting a contribution of EAT to coronary artery disease through behavior of molecule.