Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
25 巻 , 2 号
選択された号の論文の12件中1~12を表示しています
Review
  • Yoshito Yamashiro, Hiromi Yanagisawa
    2018 年 25 巻 2 号 p. 99-110
    発行日: 2018/02/01
    公開日: 2018/02/01
    [早期公開] 公開日: 2017/09/22
    ジャーナル フリー

    Thoracic aortic aneurysms (TAAs) are common, life-threatening diseases and are a major cause of mortality and morbidity. Over the past decade, genetic approaches have revealed that 1) activation of the transforming growth factor beta (TGF-β) signaling, 2) alterations in the contractile apparatus of vascular smooth muscle cells (SMCs), and 3) defects in the extracellular matrix (ECM) were responsible for development of TAAs. Most recently, a fourth mechanism has been proposed in that dysfunction of mechanosensing in the aortic wall in response to hemodynamic stress may be a key driver of TAAs. Interestingly, the elastin-contractile unit, which is an anatomical and functional unit connecting extracellular elastic laminae to the intracellular SMC contractile filaments, via cell surface receptors, has been shown to play a critical role in the mechanosensing of SMCs, and many genes identified in TAAs encode for proteins along this continuum. However, it is still debated whether these four pathways converge into a common pathway. Currently, an effective therapeutic strategy based on the underlying mechanism of each type of TAAs has not been established. In this review, we will update the present knowledge on the molecular mechanism of TAAs with a focus on the signaling pathways potentially involved in the initiation of TAAs. Finally, we will evaluate current therapeutic strategies for TAAs and propose new directions for future treatment of TAAs.

  • Hongxian Wu, Qiuna Du, Qiuyan Dai, Junbo Ge, Xianwu Cheng
    2018 年 25 巻 2 号 p. 111-123
    発行日: 2018/02/01
    公開日: 2018/02/01
    [早期公開] 公開日: 2017/10/05
    ジャーナル フリー

    Atherosclerotic cardiovascular disease (ASCVD) is an inflammatory disease characterized by extensive arterial wall matrix protein degradation. Cysteine protease cathepsins play a pivotal role in extracellular matrix (ECM) remodeling and have been implicated in the development and progression of atherosclerosis-based cardiovascular diseases. An imbalance in expression between cathepsins (such as cathepsins S, K, L, C) and their inhibitor cystatin C may favor proteolysis of ECM in the pathogenesis of cardiovascular disease such as atherosclerosis, aneurysm formation, restenosis, and neovascularization. New insights into cathepsin functions have been made possible by the generation of knockout mice and by the application of specific inhibitors. Inflammatory cytokines regulate the expression and activities of cathepsins in cultured vascular cells and macrophages. In addition, evaluations of the possibility of cathepsins as a diagnostic tool revealed that the circulating levels of cathepsin S, K, and L, and their endogenous inhibitor cystatin C could be promising biomarkers in the diagnosis of coronary artery disease, aneurysm, adiposity, peripheral arterial disease, and coronary artery calcification. In this review, we summarize the available information regarding the mechanistic contributions of cathepsins to ASCVD.

Editorial
Original Article
  • Won-tak Joo, Chan Joo Lee, Jaewon Oh, In-Cheol Kim, Sang-Hak Lee, Seok ...
    2018 年 25 巻 2 号 p. 131-141
    発行日: 2018/02/01
    公開日: 2018/02/01
    [早期公開] 公開日: 2017/07/21
    ジャーナル フリー

    Aim: The association of social networks with cardiovascular disease (CVD) has been demonstrated through various studies. This study aimed to examine the association between social network betweenness –a network position of mediating between diverse social groups–and coronary artery calcium.

    Methods: The data of 1,384 participants from the Cardiovascular and Metabolic Disease Etiology Research Center–High Risk Cohort, a prospective cohort study enrolling patients with a high risk of developing CVD (clinicaltrials.gov: NCT02003781), were analyzed. The deficiency in social network betweenness was measured in two ways: only-family networks, in which a respondent had networks with only family members, and no-cutpoint networks, in which the respondent does not function as a point of bridging between two or more social groups that are not directly connected.

    Results: Participants who had higher coronary artery calcium scores (CACSs) were likely to have a smaller network size (p<0.001), only-family networks (p<0.001), and no-cutpoint networks (p<0.001). Multiple logistic regression analyses revealed no significant association between network size and CACS. Only no-cutpoint networks had a significant relationship with CACS >400 (odds ratio, 1.72; 95% confidence interval, 1.07–2.77; p=0.026). The association was stronger among older (age >60 years) and female respondents.

    Conclusion: Deficiency in social network betweenness is closely related to coronary calcium in participants with a high risk of CVD. To generalize these results to a general population, further study should be performed.

  • Masami Sairyo, Takuya Kobayashi, Daisaku Masuda, Koutaro Kanno, Yingho ...
    2018 年 25 巻 2 号 p. 142-152
    発行日: 2018/02/01
    公開日: 2018/02/01
    [早期公開] 公開日: 2017/08/05
    ジャーナル フリー

    Aims: Fasting and postprandial hypertriglyceridemia (PHTG) are caused by the accumulation of triglyceride (TG)-rich lipoproteins and their remnants, which have atherogenic effects. Fibrates can improve fasting and PHTG; however, reduction of remnants is clinically needed to improve health outcomes. In the current study, we investigated the effects of a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), K-877 (Pemafibrate), on PHTG and remnant metabolism.

    Methods: Male C57BL/6J mice were fed a high-fat diet (HFD) only, or an HFD containing 0.0005% K-877 or 0.05% fenofibrate, from 8 to 12 weeks of age. After 4 weeks of feeding, we measured plasma levels of TG, free fatty acids (FFA), total cholesterol (TC), HDL-C, and apolipoprotein (apo) B-48/B-100 during fasting and after oral fat loading (OFL). Plasma lipoprotein profiles after OFL, which were assessed by high performance liquid chromatography (HPLC), and fasting lipoprotein lipase (LPL) activity were compared among the groups.

    Results: Both K-877 and fenofibrate suppressed body weight gain and fasting and postprandial TG levels and enhanced LPL activity in mice fed an HFD. As determined by HPLC, K-877 and fenofibrate significantly decreased the abundance of TG-rich lipoproteins, including remnants, in postprandial plasma. Both K-877 and fenofibrate decreased intestinal mRNA expression of ApoB and Npc1l1; however, hepatic expression of Srebp1c and Mttp was increased by fenofibrate but not by K-877.Hepatic mRNA expression of apoC-3 was decreased by K-877 but not by fenofibrate.

    Conclusion: K-877 may attenuate PHTG by suppressing the postprandial increase of chylomicrons and the accumulation of chylomicron remnants more effectively than fenofibrate.

  • Fumiaki Furuyama, Shinji Koba, Yuya Yokota, Fumiyoshi Tsunoda, Makoto ...
    2018 年 25 巻 2 号 p. 153-169
    発行日: 2018/02/01
    公開日: 2018/02/01
    [早期公開] 公開日: 2017/08/30
    ジャーナル フリー

    Aims: We evaluated whether exercised-based cardiac rehabilitation (CR) can ameliorate the HDL function, i.e., cholesterol efflux capacity (CEC) and paraoxonase-1 activity in patients with acute coronary syndrome (ACS).

    Methods: This study is a retrospective analysis of stored serum from patients with ACS following successful percutaneous coronary intervention. The CEC, measured by a cell-based ex vivo assay using apolipoprotein B-depleted serum and 3H-cholesterol labeled macrophages and arylesterase activity (AREA) at the onset or early phase of ACS, and the follow-up periods were compared between 69 patients who completed the five-month outpatient CR program (CR group) and 15 patients who did not participate and/or dropped out from CR program (non-CR group).

    Results: Apolipoprotein A-I (apoA-I) and CEC significantly increased by 4.0% and 9.4%, respectively, in the CR group, whereas HDL-cholesterol and AREA were not changed during the follow-up periods in both groups. Among CR patients, the CEC significantly increased, irrespective of the different statin treatment, while HDL-cholesterol and apoA-I significantly increased in patients treated with rosuvastatin or pitavastatin. Although CEC and AREA were significantly correlated each other, there is a discordance between CEC and AREA for their correlations with other biomarkers. Both CEC and AREA were significantly correlated with apoA-I rather than HDL-cholesterol. Changes in CEC and those in AREA were significantly correlated with those in apoA-I (rho=0.328, p=0.002, and rho=0.428, p<0.0001, respectively) greater than those in HDL-cholesterol (rho=0.312, p= 0.0042,and rho=0.343, p=0.003, respectively).

    Conclusions: CR can improve HDL function, and it is beneficial for secondary prevention.

  • Kentaro Watanabe, Hideki Fujii, Shunsuke Goto, Kentaro Nakai, Keiji Ko ...
    2018 年 25 巻 2 号 p. 170-177
    発行日: 2018/02/01
    公開日: 2018/02/01
    [早期公開] 公開日: 2017/07/01
    ジャーナル フリー

    Aim: Chronic kidney disease–mineral bone disorder (CKD–MBD) is associated with all-cause and cardiovascular morbidity and mortality in patients with CKD. Thus, elucidating its pathophysiological mechanisms is essential for improving the prognosis. We evaluated characteristics of CKD–MBD in a newly developed CKD rat model.

    Methods: We used male Sprague–Dawley (SD) rats and spontaneously diabetic Torii (SDT) rats, which are used as models for nonobese type 2 diabetes. CKD was induced by 5/6 nephrectomy (Nx). At 10 weeks, the rats were classified into six groups and administered with a vehicle or a low- or high-dose paricalcitol thrice a week. At 20 weeks, the rats were sacrificed; blood and urinary biochemical analyses and histological analysis of the aorta were performed.

    Results: At 20 weeks, hemoglobin A1c (HbA1c) levels, blood pressure, and renal function were not significantly different among the six groups. Serum calcium and phosphate levels tended to be higher in SDT-Nx rats than in SD-Nx rats. The urinary excretion of calcium and phosphate was significantly greater in SDT-Nx rats than in SD-Nx rats. After administering paricalcitol, serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels were significantly higher in SDT-Nx rats than in SD-Nx rats. The degree of aortic calcification was significantly more severe and the aortic calcium content was significantly greater in SDT-Nx rats than in SD-Nx rats.

    Conclusions: We suggest that our new CKD rat model using SDT rats represents a useful CKD-MBD model, and this model was greatly influenced by paricalcitol administration. Further studies are needed to clarify the detailed mechanisms underlying this model.

  • Minkyung Kim, Minjoo Kim, Hye Jin Yoo, Seung Yeon Lee, Sang-Hyun Lee, ...
    2018 年 25 巻 2 号 p. 178-185
    発行日: 2018/02/01
    公開日: 2018/02/01
    [早期公開] 公開日: 2017/07/22
    ジャーナル フリー

    Aim: Pulse wave velocity (PWV) is thought to have different relationships with metabolic syndrome (MS) components, inflammatory markers, and oxidative stress, according to age. However, age-specific determinants of PWV have not yet been studied. We investigated age-dependent relationships among PWV and MS components, inflammatory markers, and oxidative stress.

    Methods: A total of 4,318 subjects were divided into 4 groups: 19–34 y (n=687), 35–44 y (n=1,413), 45–54 y (n=1,384), and 55–79 y (n=834). MS components, brachial-ankle PWV (baPWV), high-sensitivity C-reactive protein (hs-CRP), and oxidative stress markers were measured.

    Results: There were age-related increases in MS, body mass index (BMI), waist circumference, systolic blood pressure (SBP), diastolic BP (DBP), triglycerides, glucose, hs-CRP, oxidized low-density lipoprotein (LDL), 8-epi-prostaglandin F (8-epi-PGF), and baPWV. BaPWV was significantly associated with sex and elevated BP in the 19–34 y group; with age, sex, BMI, elevated BP and triglycerides in the 35–44 y group; with age, sex, elevated BP, fasting glucose, hs-CRP and oxidized LDL in the 45–54 y group; and with age, BMI, elevated BP, fasting glucose and oxidized LDL in the 55–79 y group.

    Conclusions: Our results show that age-related increases in baPWV are associated with age-related changes in MS components, inflammatory markers, and oxidative stress. However, each of these factors has an age-specific, different impact on arterial stiffness. In particular, oxidative stress may be independently associated with arterial stiffness in individuals older than 45 y.

  • Sentaro Suzuki, Hisatomi Arima, Soichiro Miyazaki, Akira Fujiyoshi, Ay ...
    2018 年 25 巻 2 号 p. 186-198
    発行日: 2018/02/01
    公開日: 2018/02/01
    [早期公開] 公開日: 2017/07/26
    ジャーナル フリー

    Aim: There are few data regarding associations between sleep duration and subclinical atherosclerosis in Japan. The aim of this study was to evaluate associations of self-reported sleep duration with calcification in the coronary arteries (CAC) and carotid intima media thickness (IMT) in Japanese men.

    Methods: This was a cross-sectional survey of 1093 randomly selected men from Kusatsu City, Japan. Average sleep duration on weekdays was estimated through questionnaire; CAC by computed tomography; and carotid IMT by ultrasonography.

    Results: The prevalence of CAC was 50.0% for participants with sleep duration <5.5 h, 43.9% with 5.5–6.4 h, 50.0% with 6.5–7.4 h, 49.3% with 7.5–8.4 h, and 62.5% with ≥8.5 h. In univariate analysis, participants with sleep duration ≥8.5 h had significantly higher prevalence of CAC than those with 6.5–7.4 h (p=0.043). After adjustment for age and other risk factors, however, the association was not significant (p=0.776). The average IMT was 0.85 mm for participants with sleep duration <5.5 h, 0.83 mm with 5.5–6.4 h, 0.85 mm with 6.5–7.4 h, 0.88 mm with 7.5–8.4 h, and 0.90 mm with ≥8.5 h. None of the differences in IMT observed in crude or multivariable-adjusted analyses was significant (all p>0.1).

    Conclusion: Self-reported sleep duration was not associated with increased CAC or carotid IMT in a general population of Japanese men.

Correspondence
feedback
Top