Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Volume 18 , Issue 4
Showing 1-11 articles out of 11 articles from the selected issue
Review
  • Selvakumar Velu, Gregory YH Lip
    Type: Review
    2011 Volume 18 Issue 4 Pages 257-273
    Published: 2011
    Released: April 27, 2011
    [Advance publication] Released: November 13, 2010
    JOURNALS FREE ACCESS
    Atrial fibrillation (AF) is becoming a major health care burden as elderly populations increase. The increased risk of stroke and thromboembolisms in patients with AF is well documented and antico-agulation with adjusted-dose warfarin is highly effective in reducing stroke risk, being superior to antiplatelet agents. Despite recognition of the epidemiological problem and the sound evidence base for thromboprophylaxis, as well as major guidelines recommending treatment, anticoagulation use is still suboptimal, given the dis-utility and limitations associated with warfarin. Recent developments in thromboprophylaxis for AF include efforts for better risk stratification for predictions of thromboembolic risk. Constant efforts are underway to develop newer, less cumbersome, alternatives to warfarin with similar (or better) efficacy. This review article provides an overview of the recent progress made, the potential challenges involved and the future of these therapeutic approaches.
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  • Nobukiyo Tanaka, Sumiko Abe-Dohmae, Noriyuki Iwamoto, Shinji Yokoyama
    Type: Review
    2011 Volume 18 Issue 4 Pages 274-281
    Published: 2011
    Released: April 27, 2011
    [Advance publication] Released: December 14, 2010
    JOURNALS FREE ACCESS
    ATP-binding cassette transporter (ABC) A7 is an ABC family protein that is a so-called full-size ABC transporter, highly homologous to ABCA1, which mediates the biogenesis of high-density lipoprotein (HDL) with cellular lipid and helical apolipoproteins. ABCA7 mediates the formation of HDL when exogenously transfected and expressed; however, endogenous ABCA7 was shown to have no significant impact on the generation of HDL and was found to be associated with phagocytosis regulated by sterol regulatory element binding protein 2. Since phagocytosis is one of the fundamental functions of animal cells as an important responsive reaction to infection, injury and apoptosis, ABCA7 seems to be one of the key molecules linking sterol homeostasis and the host defense system. In this context, HDL apolipoproteins were shown to enhance phagocytosis by stabilizing ABCA7 against calpain-mediated degradation and increasing its activity, shedding light on a new aspect of the regulation of the host-defense system.
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Original Article
  • Fu-Jiang Chu, Xiao-Bao Jin, Jia-Yong Zhu
    Type: Original Article
    2011 Volume 18 Issue 4 Pages 282-290
    Published: 2011
    Released: April 27, 2011
    [Advance publication] Released: December 10, 2010
    JOURNALS FREE ACCESS
    Aim: To investigate the effects of housefly maggot (Musca domestica) protein-enriched fraction/extracts (PE) on lipopolysaccharide (LPS)-induced atherosclerosis (AS) pro-inflammatory responses in mice and macrophages.
    Methods: The mouse model of AS was established by feeding a cholesterol-enriched diet and inducing by LPS. Changes in the levels of blood lipids (total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL)) and pro-inflammatory cytokines (interferon-gamma (IFNγ), tumor necrosis factor alpha (TNFα) and interleukin-1alpha (IL-1α)) were determined. Histomorphometric analysis of the pathological condition of the artery was also carried out. The macrophages were stimulated by LPS in the presence or absence of PE, and then the levels of TNFα, IL-1α and monocyte chemotactic protein 1 (MCP-1) in cell culture supernatant were measured.
    Results: Compared with the negative control group, the levels of three pro-inflammatory cytokines were significantly enhanced in the PE treatment group (p< 0.01). The concentrations of TC, TG and LDL were lower in the PE treatment group than in the negative control group (p< 0.01). HDL concentration in the PE treatment group was higher than in the negative control group (p< 0.01). Histomorphometric analysis showed that the thickness of the intima and media area, as well as the area ratio of the intima to media in the PE treatment group were lower than in the negative control group (p< 0.01). The expression of TNFα, IL-1α and MCP-1 in LPS-induced macrophages was inhibited by different concentrations of PE (p< 0.01).
    Conclusion: These results indicate that PE potently inhibited multiple pro-inflammatory responses in experimental atherosclerosis lesions in vivo, and possessed anti-pro-inflammatory properties in vitro.
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  • Hideyuki Kanda, Peiyu Wang, Tomonori Okamura, GaoWa Wuyun, HePing Wu, ...
    Type: Original Article
    2011 Volume 18 Issue 4 Pages 291-297
    Published: 2011
    Released: April 27, 2011
    [Advance publication] Released: December 10, 2010
    JOURNALS FREE ACCESS
    Aim: The World Health Organization (WHO) includes insulin resistance among its criteria for diagnosing metabolic syndrome (MetS); however, previous epidemiologic studies have limited their research to settled populations only. This study aims to clarify the relationship between plasma insulin and metabolic factors on a broader scale by studying data obtained from nomadic and settled Mongolian populations.
    Methods: A cross-sectional epidemiologic study of 200 nomads and 256 farmers was performed in Inner Mongolia, Republic of China. Plasma insulin levels and other metabolic factors, such as blood pressure, serum lipids and obesity, were measured. Participants were classified into 3 categories according to their plasma insulin levels.
    Results: Cut-off values grouped into tertiles of fasting insulin for all participants were 6.73 nmol/L and 10.33 nmol/L. The mean number of metabolic risk factors, waist circumference, fasting plasma glucose and triglyceride were higher, and the mean HDL cholesterol was lower in the higher fasting insulin tertile among farmers after adjusting for age, gender, smoking, alcohol drinking and total cholesterol. However, no MetS factors were statistically related with fasting insulin tertile levels among nomads.
    Conclusions: In nomads, hyperinsulinemia may not be an indicator of MetS due to their specific life-style.
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  • Yuya Matsue, Makoto Suzuki, Masami Abe, Maki Ono, Mie Seya, Tomofumi N ...
    Type: Original Article
    2011 Volume 18 Issue 4 Pages 298-304
    Published: 2011
    Released: April 27, 2011
    [Advance publication] Released: January 06, 2011
    JOURNALS FREE ACCESS
    Aim: Atrial fibrillation (AF), regardless of subtype, is associated with a prothrombotic state, which is related to endothelial dysfunction (ED).We hypothesized that paroxysmal atrial fibrillation (PAF) patients have endothelial dysfunction, and this may partially explain the high thromboembolic risk and poorer outcome in this category of patients.
    Methods: The study population consisted of 100 consecutive outpatients with AF (mean age 65.9±7.9 years; 68 (68%) male) and 21 characteristics and comorbidity matched control subjects (mean age 64.8±7.0 years; 13 (61.9%) male). AF patients were divided into the PAF group (n=50) and permanent/persistent AF (PeAF) group (n=50).Reactive hyperemia pulse amplitude tonometry index (RHI) was measured to evaluate endothelial function.
    Results: RHI was significantly lower in the PAF (1.67±0.30) and PeAF (1.63±0.28) groups in comparison with control subjects (2.12±0.40, both p< 0.001). There was no significant difference in RHI between the PAF and PeAF groups (p= 0.88). On linear regression analysis, both PeAF and PAF are significant independent predictors of RHI.
    Conclusions: In conclusion, ED in PAF patients was comparable to PeAF patients, and the presence of PAF itself is a contributing factor for ED independent of other coexisting comorbidities. This may provide a mechanism explaining why the risk of thromboembolism in PAF is comparable with PeAF patients.
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  • Phan Nguyen Thanh Binh, Yasunori Abe, Pham Gia Tien, Le Nguyen Trung D ...
    Type: Original Article
    2011 Volume 18 Issue 4 Pages 305-311
    Published: 2011
    Released: April 27, 2011
    [Advance publication] Released: January 12, 2011
    JOURNALS FREE ACCESS
    Aim: The Vietnamese develop type 2 diabetes (T2D) and metabolic syndrome (MS) at a lower BMI than other ethnicities. Thus, biomarkers that identify subjects at an increased risk of T2D independently of obesity are being sought. Recent studies show that circulating NO metabolites (NOx) are increased in T2D. We investigated whether plasma NOx levels predict insulin resistance and glucose intolerance before the development of T2D, independently of obesity.
    Methods: The current study was derived from a population-based study in HCMC, Vietnam, which was designed to investigate the prevalence of MS and T2D in a population aged 30-69 years. Four hundred and twenty-two subjects were recruited from the study and were stratified into 4 age- and gender-matched groups according to a glucose tolerance test {normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and T2D}.
    Results: Plasma NOx concentrations were significantly increased in T2D but not in IFG or IGT compared with NGT. Multiregression analysis showed that plasma NOx levels were inversely correlated with BMI in T2D whereas no association was found between plasma NOx levels and BMI in non-diabetic subjects. Moreover, there was no correlation between plasma NOx levels and homeostasis model assessment-insulin resistance (HOMA-IR) in both diabetic and non-diabetic subjects.
    Conclusion: Plasma NOx levels did not predict glucose intolerance or insulin resistance before the development of T2D and the increase in plasma NOx levels in T2D was not caused by adiposity. Thus, plasma NOx is not a useful marker for the prediction of high-risk subjects for T2D among Vietnamese.
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  • Hiroaki Shiraishi, Kazuhisa Ikemoto, Shin Tada, Yasuhiro Udagawa, Masa ...
    Type: Original Article
    2011 Volume 18 Issue 4 Pages 312-317
    Published: 2011
    Released: April 27, 2011
    [Advance publication] Released: January 06, 2011
    JOURNALS FREE ACCESS
    Aims: Cilostazol, a type III phosphodiesterase inhibitor, is utilized for the treatment of intermittent claudication and is considered to have the beneficial effects against the atherogenic process. In the present study, we examined the effects of cilostazol on BH4 biosynthesis in HUVEC treated with a mixture of the pro-inflammatory cytokines IFN-γ and TNF-α.
    Methods: Isolated HUVECs were grown to confluence and treated with IFN-γ (300 units/mL) and TNF-α (300 units/mL) for 16 h in order to stimulate BH4 biosynthesis. The BH4 levels were mea-sured by HPLC. The mRNA expression of GTP cyclohydrolase I (GTPCH), the rate-limiting enzyme of BH4 biosynthesis, and GTPCH feedback regulatory protein (GFRP) were quantified by real-time PCR. The GTPCH protein expression was assessed by western blot analysis.
    Results: Cilostazol significantly reduced the BH4 levels in cytokine-stimulated HUVEC. Cilostazol produced a concomitant increase in the cAMP levels in HUVEC. Cilostazol decreased the GTPCH activity as well as the expression of GTPCH mRNA and protein. 8-bromo-cAMP (8Br-cAMP), a cell-permeable cAMP analogue, did not reproduce the effects of cilostazol. Cilostazol did not affect the cytokine-induced inhibition of GFRP mRNA expression.
    Conclusions: We conclude that cilostazol inhibited cytokine-stimulated BH4 biosynthesis via a cAMP-independent mechanism in HUVEC. Our data indicate that cilostazol reduced GTPCH activity and did so by suppressing the GTPCH protein levels.
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  • Collin L. Ellis, Indika Edirisinghe, Tissa Kappagoda, Britt Burton-Fre ...
    Type: Original Article
    2011 Volume 18 Issue 4 Pages 318-327
    Published: 2011
    Released: April 27, 2011
    [Advance publication] Released: January 13, 2011
    JOURNALS FREE ACCESS
    Aim: A pro-thrombotic, pro-inflammatory diet can play a causative role in atherosclerotic-cardiovascular diseases. Dietary intervention studies provide insight into their pathophysiological manifestations and opportunities for prevention and management. We previously showed in an acute-meal setting that a beverage containing polyphenolic- and antioxidant-rich strawberry (Fragaria) vs placebo attenuated postprandial (fed-state) increases in biomarkers of oxidative and inflammatory stress, and insulin concentrations, induced by a high carbohydrate/fat (HCF) meal.
    In the present study, we aimed to extend our findings and investigate hypotheses related to the effects of chronic/6-week (wk) strawberry consumption on HCF meal-induced increases in glucose, insulin, and indicators of inflammation and hemostasis.
    Methods: In a crossover design, 14 women and 10 men (mean age, BMI: 50.9±15 years, 29.2±2.3 kg/m2, respectively), were randomized to a 6-wk strawberry or placebo beverage followed by an HCF meal with assessments for 6-hours (h) postprandially.
    Results: HCF meal responses after 6-wk strawberry beverage showed significantly attenuated postprandial PAI-1 concentrations compared to the placebo (p =0.002); the difference was most notable at 6 h. The IL-1 β response was attenuated with strawberry compared to the placebo (p =0.05). IL-6 attenuation was apparent but non-significant; IL-6 rose significantly from baseline to 6 h after the HCF meal following a placebo (p ≤0.01), although it remained relatively flat following the strawberry beverage from fasting to 6 h. No significant treatment-related differences were apparent for platelet aggregation, hsCRP, TNF-α, insulin, or glucose.
    Conclusion: These data are the first to suggest that regular consumption of strawberry, a polyphenolic- and antioxidant-rich fruit, may provide protection from HCF meal-induced increases in fibrinolytic and inflammatory factors in at-risk men and women.
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  • Kwang Joon Kim, Byung-Wan Lee, Hyun-min Kim, Joo Youn Shin, Eun Seok K ...
    Type: Original Article
    2011 Volume 18 Issue 4 Pages 328-336
    Published: 2011
    Released: April 27, 2011
    [Advance publication] Released: January 06, 2011
    JOURNALS FREE ACCESS
    Aim: Type 2 diabetes mellitus (T2DM) is a risk factor for increased arterial stiffness. We evaluated associations between the cardio-ankle vascular index (CAVI) and carotid plaque, intima media thickness (IMT), and diabetic microvascular complications in Korean T2DM patients.
    Methods: We conducted a retrospective, cross-sectional study of 320 Korean T2DM patients without a history of macrovascular disease or macroalbuminuria. We measured 24-hour urinary albumin excretion (UAE) levels and performed funduscopic and neuropathy examinations to assess the extent of diabetic microvascular complications. Arterial stiffness was assessed using CAVI. We also measured the ankle-brachial index (ABI), common carotid artery IMT, and carotid beta stiffness index.
    Results: Among the 320 patients enrolled in this study, 64 (20%) had increased CAVI (≥ 9). We found that CAVI was correlated with systolic blood pressure, pulse pressure, IMT, carotid beta stiffness index, log-transformed UAE, and total cholesterol. In multiple logistic regression analysis, mean IMT and the presence of carotid plaque were independently associated with increased CAVI (≥ 9) (OR=5.77, P < 0.01; OR=5.36, P < 0.001, respectively). Furthermore, an increased CAVI was associated with peripheral neuropathy (OR=2.03, P = 0.03) and microalbuminuria (OR=2.47, P < 0.01) after adjusting for possible confounding variables.
    Conclusions: The results of this study suggest that increased CAVI is associated with the presence of arterial plaque, increased IMT, and microvascular complications, such as nephropathy and neuropathy, in T2DM patients.
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  • Yoko Irie, Kenya Sakamoto, Fumiyo Kubo, Takahiro Okusu, Takashi Katura ...
    Type: Original Article
    2011 Volume 18 Issue 4 Pages 337-344
    Published: 2011
    Released: April 27, 2011
    [Advance publication] Released: January 06, 2011
    JOURNALS FREE ACCESS
    Aims: Carotid atherosclerosis assessed by ultrasound is an established surrogate marker for systemic atherosclerosis. This study aimed to evaluate the association between coronary artery stenosis assessed by coronary computed tomography angiography (CCTA) and intima-media thickness (IMT) in asymptomatic type 2 diabetic patients.
    Methods: In a cross-sectional study, carotid IMT was measured by ultrasound and CCTA in 169 asymptomatic type 2 diabetic patients.
    Results: Among 169 patients, 77 (46%) had coronary artery stenosis on CCTA. Multivariate logistic regression analysis revealed four independent predictors of coronary artery stenosis: diabetes duration (OR 4.07, 95%CI 2.34-7.12; p< 0.001), gender (OR 1.66, 95% CI 1.05-2.61; p=0.029), dyslipidemia (OR 2.07, 95%CI 1.34-3.18; p=0.001), and max-IMT (OR 2.71, 95%CI 1.70-4.33; p< 0.001). By ROC curve analyses, the area under the curve (AUC) for max-IMT was 0.73 (95%CI 0.66-0.81; p< 0.001) and mean-IMT was 0.64 (95%CI 0.56-0.73; p=0.001). The cut-off level for the greatest sensitivity and specificity for max-IMT was 1.55 mm (sensitivity 0.90, specificity 0.46), and mean-IMT was 1.05 mm (sensitivity 0.55, specificity 0.72).
    Conclusion: Carotid IMT was associated with coronary artery stenosis assessed by CCTA in asymptomatic type 2 diabetic patients. Measurement of both mean- and max-carotid IMT is useful for selecting asymptomatic type 2 diabetic patients who should undergo CCTA screening.
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  • Emiko Saito, Tomoo Okada, Yuriko Abe, Yuki Kuromori, Michio Miyashita, ...
    Type: Original Article
    2011 Volume 18 Issue 4 Pages 345-350
    Published: 2011
    Released: April 27, 2011
    [Advance publication] Released: February 05, 2011
    JOURNALS FREE ACCESS
    Aims: In obesity, fatty acid composition is altered with reduced docosahexaenoic acid (DHA) levels. Desaturating enzymes, stearoyl-CoA desaturase (SCD), delta-6 desaturase (D6D) and delta-5 desaturase (D5D) modulate fatty acid composition and are thus associated with the development of metabolic syndrome. The aim of this study was to identify the relationships among DHA content, desaturase indices and the components of metabolic syndrome in childhood obesity.
    Methods: Thirty-two obese children (27 male, 5 female) aged 12.0±2.6 years (mean±SD), with a relative body weight greater than 120% of the standard weight for sex, age and height, were recruited. Fatty acid composition of plasma phospholipids was analyzed by gas chromatography, and the desaturase indices were assessed: SCD (16:1n-7/16:0 and 18:1n-9/18:0), D6D (20:3n-6/18:2n-6) and D5D (20:4n-6/20:3n-6).
    Results: No sex difference was observed in fatty acid composition. DHA content tended to have an inverse association with body mass index (BMI) (r=−0.337, p=0.0592), and correlated significantly with very low-density lipoprotein-triglyceride (r=−0.558, p=0.0057). In addition, DHA content had significant negative relationships with SCD indices (SCD16; r=−0.373, p=0.0357 and SCD18; r=−0.580, p=0.0005), which correlated positively with BMI(r=0.439, p=0.0120, r=0.353, p=0.0473, respectively), but had no association with D5D or D6D.
    Conclusions: DHA content in obese children was independent of the desaturation of alpha-linolenic acid. Reduced DHA content was associated with increased SCD index, and might contribute to the development of metabolic syndrome. Dietary management including fatty acids is suggested to be important to prevent and better manage obesity.
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