Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Volume 16 , Issue 5
Showing 1-23 articles out of 23 articles from the selected issue
Reviews
  • Ken-ichi Aihara, Hiroyuki Azuma, Masashi Akaike, Masataka Sata, Toshio ...
    Type: Review
    2009 Volume 16 Issue 5 Pages 523-531
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: September 03, 2009
    JOURNALS FREE ACCESS
    Heparin cofactor II (HCII) specifically inhibits thrombin action at the site of vascular wall injury. We encountered a congenital HCII deficiency patient with advanced multiple atherosclerotic lesions. This patient led us to conduct clinical studies to examine the role of HCII against atherosclerosis. We found that the incidence of in-stent restenosis after percutaneous coronary intervention, severity of carotid atherosclerosis and prevalence of peripheral arterial disease are inversely associated with plasma HCII activity. In order to clarify the vascular protective action of HCII, we generated HCII- deficient mice by gene targeting. In contrast to a previous study, HCII-/- mice were embryonically lethal. In HCII+/- mice, accelerated intimal hyperplasia and frequent thrombosis were observed after cuff or wire injury of femoral arteries. The number of protease-activated receptor-1 (PAR-1) -positive cells and the gene expression levels of inflammatory cytokines and chemokines were increased in the thickened vascular walls of HCII+/- mice. The accelerated intimal hyperplasia in HCII+/- mice with vascular injury was attenuated by human HCII administration. Furthermore, HCII deficiency exaggerated aortic plaque formation with increased oxidative stress in apolipoprotein E-/- mice. These results demonstrate that HCII protects against thrombin-induced vascular remodeling in both humans and mice and suggest that HCII is a predictive biomarker and therapeutic target for atherosclerosis.
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  • Takahito Kondo, Makoto Hirose, Kan Kageyama
    Type: Review
    2009 Volume 16 Issue 5 Pages 532-538
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: September 14, 2009
    JOURNALS FREE ACCESS
    Oxidative stress is believed to be a cause of aging and cardiovascular disorders. In response to inflam-mation or endothelial cell injury, production of reactive oxygen species (ROS) is enhanced in vascular cells. These changes contribute to the initiation of atherosclerosis. Vascular cells possess anti-oxidant systems to protect against oxidative stress, in addition to the redox system. The redox status of pro-tein thiols is important for cellular functions. The Akt signaling pathway exerts effects on survival and apoptosis, and is regulated by the glutathione (GSH)/glutaredoxin (GRX)-dependent redox sys-tem. Sex hormones such as estrogens protect against oxidative stress by protecting the Akt signaling pathway but the physiological role of the extracellular GSH/GRX system has not been clarified, although found an increase in the levels of S-glutathionylated serum proteins in patients with athero-sclerosis obliterans. The results suggested that impaired serum redox potential is a marker of the development vascular dysfunction and estrogen has a possible role in the prevention of atherosclerosis.
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Original Articles
  • Yoh Miyashita, Kei Endo, Atsuhito Saiki, Noriko Ban, Takashi Yamaguchi ...
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 539-545
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: November 10, 2009
    JOURNALS FREE ACCESS
    Aim: A novel device has been developed for measuring the cardio-ankle vascular index (CAVI) as an indicator of arterial stiffness. In this study, we evaluated the effect of pitavastatin on CAVI in type 2 diabetic patients.
    Methods: Forty-five type 2 diabetes mellitus patients with low-density lipoprotein cholesterolemia were enrolled and treated with pitavastatin 2 mg/day for 12 months. Before and after pitavastatin administration, HbA1c, serum lipids, serum malondialdehyde-LDL (MDA-LDL), urinary 8-hydroxy- 2'-deoxyguanosine (8-OHdG) and CAVI were measured.
    Results: After pitavastatin treatment for 12 months, significant decreases in 8-OHdG, MDA-LDL and CAVI were observed. ΔCAVI significantly correlated with ΔMDA-LDL.
    Conclusions: In type 2 diabetic patients, pitavastatin may have an oxidative stress-reducing effect, especially in a state of enhanced oxidative stress, and CAVI may be useful as a routine test for the diagnosis and therapeutic monitoring of atherosclerosis.
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  • Takashi Motomura, Maki Okamoto, Tetsuhiro Kitamura, Hiroyasu Yamamoto, ...
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 546-552
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: September 03, 2009
    JOURNALS FREE ACCESS
    Aim: Previous studies have been inconsistent results about the effects of statins on serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and high sensitivity C-reactive protein (hsCRP) levels. We therefore investigated the effects of pitavastatin on serum lipid profiles and hsCRP levels in patients with type 2 diabetes mellitus.
    Methods: The study population was 65 Japanese type 2 diabetic patients who had been administered 2 mg daily of pitavastatin and completed a 6-month follow-up. Serum lipids and hsCRP were measured before and after treatment for 1, 3, and 6 months.
    Results: Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and TG had significantly reduced after 1 month and remained reduced for 6 months, while HDL-C levels had significantly increased after 1 month and remained at the higher level for 6 months. Baseline median levels of hsCRP were 0.49 mg/L and showed a significant reduction to 0.37 mg/L at 6 months' treatment (p<0.001). Six-month changes in hsCRP levels were not associated with those in TC, LDL-C, HDL-C or TG.
    Conclusion: Pitavastatin improved serum lipid profiles and reduced serum hsCRP levels in type 2 diabetic patients with relatively low inflammation. The effect on hsCRP was not related to the effects on serum lipid profiles.
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  • Daisuke Fujimatsu, Norihiko Kotooka, Teruo Inoue, Masanori Nishiyama, ...
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 553-559
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: November 10, 2009
    JOURNALS FREE ACCESS
    Aim: Low plasma adiponectin levels have been demonstrated to be linked to obesity and insulin resistance. It has also been suggested that high molecular weight (HMW) adiponectin is more important for vascular protection than the total amount of adiponectin, although clinical data of HMW adiponectin are lacking. The purpose of this study was to investigate HMW adiponectin levels in Japanese rural residents and to elucidate their clinical significance.
    Methods: We measured plasma HMW adiponectin levels in 1,183 subjects (643 men) who participated in our annual health check program in Kashima-city, Saga, Japan.
    Results: The median plasma level of HMW adiponectin was significantly lower in men than women (2.6, 1.64.0 vs 6.5, 3.78.6 μg/mL, p<0.001), respectively. Multivariate linear regression analysis showed that body weight, B-type natriuretic peptide (BNP) and high density lipoprotein cholesterol were independently associated with HMW adiponectin in both genders. Triglyceride and serum creatinine levels were associated with HMW adiponectin in men only.
    Conclusions: HMW adiponectin levels were lower in men than in women and were associated with BNP independently. A prospective follow-up of the subjects in this study is required to determine the usefulness of HMW adiponectin as a biomarker for predicting the development of cardiovascular disease.
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  • Osamu Hanyu, Junko Yoshida, Eri Abe, Satoshi Hirayama, Kazunori Miyake ...
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 560-567
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: September 14, 2009
    JOURNALS FREE ACCESS
    Aim: The elevation of high-sensitivity C-reactive protein (hs-CRP) is a strong risk factor for cardio-vascular disease (CVD) and is associated with insulin resistance. The hs-CRP concentration also increases in smokers known to be at a high risk for CVD. We examined whether hs-CRP concentra-tion reflects insulin resistance in smokers.
    Methods: The hs-CRP levels were measured in 121 male subjects (54 nonsmokers and 67 smokers) with a normal glucose tolerance. The hs-CRP concentration was compared to the homeostasis model assessment of insulin resistance (HOMA-IR) and other clinical variables related to insulin resistance.
    Results: Smokers had a 64.5% higher hs-CRP concentration than nonsmokers (p<0.0001). In both nonsmokers and smokers, hs-CRP positively correlated with HOMA-IR (r=0.301, p<0.05 and r=0.312, p<0.01) and fasting insulin (r=0.281, p<0.05 and r=0.356, p<0.01). The correlation between hs-CRP and HOMA-IR or fasting insulin was stronger in smokers than in nonsmokers. In smokers, hs-CRP significantly correlated with BMI and HDL-cholesterol (r=0.386, p<0.01 and r=-0.307, p<0.05). Stepwise regression analysis revealed that BMI and HOMA-IR were significant predictors of hs-CRP in smokers (r=0.423, p<0.01).
    Conclusions: The hs-CRP concentration reflects insulin resistance in smokers. It would be preferable to consider insulin resistance in evaluating hs-CRP concentrations, even in smokers.
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  • Hidehisa Sasaki, Atsuhito Saiki, Kei Endo, Noriko Ban, Takashi Yamaguc ...
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 568-575
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: September 14, 2009
    JOURNALS FREE ACCESS
    Aim: The three types of calcium channel blocker (CCB), L-, T- and N-type, possess heterogeneous actions on endothelial function and renal microvascular function. In the present study, we evaluated the effects of two CCBs, efonidipine and amlodipine, on renal function and arterial stiffness.
    Methods: Forty type 2 diabetic patients with hypertension and nephropathy receiving angiotensin receptor II blockers were enrolled and randomly divided into two groups: the efonidipine group was administered efonidipine hydrochloride ethanolate 40 mg/day and the amlodipine group was admin-istered amlodipine besilate 5 mg/day for 12 months. Arterial stiffness was evaluated by the cardio-ankle vascular index (CAVI).
    Results: Changes in blood pressure during the study were almost the same in the two groups. Sig-nificant increases in serum creatinine and urinary albumin and a significant decrease in the esti-mated glomerular filtration rate were observed in the amlodipine group, but not in the efonidipine group. On the other hand, significant decreases in plasma aldosterone, urinary 8-hydroxy-2'-deoxy-guanosine and CAVI were observed after 12 months in the efonidipine group, but not in the amlo-dipine group.
    Conclusions: These results suggest that efonidipine, which is both a T-type and L-type calcium chan-nel blocker, has more favorable effects on renal function, oxidative stress and arterial stiffness than amlodipine, an L-type calcium channel blocker.
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  • Fumiko Nagatomo, Ning Gu, Hidemi Fujino, Isao Takeda, Kinsuke Tsuda, A ...
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 576-585
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: September 18, 2009
    JOURNALS FREE ACCESS
    Aim: Data on the skeletal muscle characteristics of patients and animals with lifestyle-related diseases are limited. We investigated mRNA expression levels and fiber profiles in the skeletal muscles of rats with obesity, diabetes, hypertension, and/or hyperlipidemia.Methods: The mRNA expression levels of peroxisome proliferator-activated receptors (PPARα and PPARδ/β), PPARγ coactivator-1α (PGC-1α), stearoyl-CoA desaturase-1 (SCD-1), carnitine palmi-toyl-transferase I (CPT I), medium-chain acyl-CoA dehydrogenase (MCAD), and mitochondrial transcriptional factor A (TFAM) in the soleus muscles were compared among 15-week-old control (WR), type 2 diabetic (GK), hypertensive (SHR), and hyperlipidemic (CP) rats. The fiber profiles in the soleus muscles of these rats were also determined.Results: GK rats showed lower PPARδ/β, PGC-1α, and MCAD expression levels than WR rats. SHR rats showed higher PPARα and MCAD and lower PPARδ/β expression levels than WR rats. CP rats showed lower PPARδ/β and higher SCD-1 expression levels than WR rats. The muscles of WR, SHR, and CP rats had low-oxidative type I and high-oxidative type IIA and type IIC fibers, whereas the muscle of GK rats had only low-oxidative type I fibers.Conclusions: The skeletal muscles of rats with lifestyle-related diseases have unique mRNA expres-sion patterns and fiber profiles depending on the type of disease. For example, the lower PGC-1α and MCAD mRNA expression levels in the soleus muscles of type 2 diabetic rats are associated with the presence of only low-oxidative type I fibers in the muscle.
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  • Hirokazu Mitsuoka, Masako Toyohara, Noriaki Kume, Kazutaka Hayashida, ...
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 586-593
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: September 03, 2009
    JOURNALS FREE ACCESS
    Aim: Diagnostic values of soluble SR-PSOX/CXCL16 (sSR-PSOX/CXCL16), a receptor for atherogenic oxidized LDL and a membrane-anchored chemokine for CXCR6-positive lymphocytes, for acute coronary syndrome (ACS) were evaluated.
    .Methods: We examined 106 patients undergoing coronary angiography (CAG); 17 patients with ACS and 89 patients without ACS (non-ACS) including stable angina. Circulating sSR-SPOX/CXCL16 was measured in peripheral venous blood by sandwich ELISA.
    Results: Age, gender, prevalence of diabetes or hypertension, and serum lipid profiles were not significantly different between ACS and non-ACS. Presence or absence of risk factors, such as diabetes, smoking and hypertension, did not significantly affect circulating sSR-PSOX/CXCL16 levels. Circulating sSR-PSOX/CXCL16 levels were significantly lower in ACS than non-ACS (median: 3.05 versus 3.36 ng/mL, p<0.02). Lipid profiles, high-sensitivity C-reactive protein (hs-CRP), cardiac troponin T (TnT), and soluble LOX-1 (sLOX-1) showed no significant correlation with sSR-PSOX/CXCL16. Receiver-operating characteristic (ROC) curves for ACS detection indicate higher sensitivity and specificity for sSR-PSOX/CXCL16 than hs-CRP. In the TnT-negative and sLOX-1-negative subpopulation, sSR-PSOX/CXCL16 showed similar sensitivity and specificity for ACS; however, hs-CRP showed less sensitivity and specificity for ACS when compared with the whole population.
    Conclusion: sSR-PSOX/CXCL16 is a biomarker for ACS, which would provide additional diagnostic information besides TnT and sLOX-1.
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  • Kotaro Aihara, Hideto Ishii, Masayuki Yoshida
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 594-603
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: November 10, 2009
    JOURNALS FREE ACCESS
    Aim: A food-derived bioactive tripeptide, Val-Pro-Pro (VPP), has been shown to possess angiotensin I-converting enzyme (ACE) inhibitory activity and foods containing such peptides exhibit an anti-hypertensive effect in clinical settings.
    Methods: The present study focused on the effect of VPP on monocyte adhesion to endothelium under flow conditions using phorbol 12-myristate 13-acetate (PMA)-stimulated monocytic THP-1 cells.
    Results: Pre-incubation of THP-1 cells with VPP (1 mM, 24 hours) significantly decreased the PMA-induced adhesion of THP-1 cells (p<0.05) to human umbilical vein endothelial cells (HUVECs). PMA-induced up-regulation of β1 and β2 integrin activation in THP-1 cells was downregulated by VPP, which significantly suppressed only the PMA-induced phosphorylation of JNK (p<0.05) in THP-1 cells. In addition, preincubation of THP-1 with SP600125, a specific inhibitor of JNK, resulted in significant reduction of the PMA-induced adhesion of THP-1. Interestingly, another tripeptide with comparable ACE inhibitory activity, Leu-Gly-Pro (LGP), failed to reduce the PMA-induced adhesion of THP-1, suggesting a distinct anti-inflammatory effect of VPP on THP-1 adhesion.
    Conclusion: These observations suggest that VPP moderates monocyte adhesion to inflamed endothelia via attenuation of the JNK pathway in monocytes, which might contribute to the primary prevention of atherosclerosis.
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  • Maria Kimouli, Spiros Miyakis, Petros Georgakopoulos, Eirini Neofytou, ...
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 604-610
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: September 16, 2009
    JOURNALS FREE ACCESS
    Aim: The chemokine fractalikine is expressed in vascular endothelium, exerting a pro-atherogenic effect. Two single-nucleotide polymorphisms of the CX3CR1 gene (T280M and V249I) affect frac-talkine receptor expression and function. We aimed to assess the prevalence of CX3CR1 polymor-phisms and the association with ischemic cerebrovascular attacks in a cohort of carotid atheromatous disease patients and age-matched controls.
    Methods: Using PCR-RFLP, we analyzed allelotypes for T280M and V249I in 150 patients with and 151 controls without carotid atherosclerosis assessed using carotid duplex ultrasound; the subjects were patients admitted for any reason to a tertiary hospital. Genotype data were compared with modifiable risk factors for cerebrovascular disease and the reason for admission, using ischemic stroke as an endpoint. Stroke types associated with carotid atherosclerosis were analysed separately.
    Results: The M280 allelic frequency was lower among carotid atherosclerosis patients than controls (0.15 versus 0.23, adjusted OR 0.47, 95% CI 0.30-0.74). Absence of M280 allele was an indepen-dent factor associated with carotid atherosclerosis (OR 3.70, 95% CI 1.92-7.14), stronger than hypertension, dyslipidemia, diabetes and cigarette smoking. The I249 allele was also under-repre-sented in carotid atherosclerosis; this was not statistically significant. T280M and V249I genotypes were not associated with admission due to ischemic stroke of the large vessel subtype (TOAST classi-fication, 73 episodes), whereas carotid atherosclerosis, previous ischemic event, age, hypertension, diabetes, hyperlipidemia and cigarette smoking were all independently associated.
    Conclusions: The M280 fractalkine receptor gene allele is associated with a lower risk of carotid ath-eromatous disease, independent from the modifiable cerebrovascular risk factors.
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  • Li Tian, Yanhua Xu, Mingde Fu, Lianqun Jia, Yuye Yang
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 611-620
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: September 03, 2009
    JOURNALS FREE ACCESS
    Aim: To demonstrate the interrelationship between plasma apolipoprotein(apo)CII concentrations and the pattern of high-density lipoprotein (HDL) subclass distribution.
    Methods: ApolipoproteinA-I contents of plasma HDL subclasses were quantified by 2-dimensional gel electrophoresis associated with immunodetection in 504 Chinese subjects.
    Results: Compared with subjects in the lowest tertile of the apoCII group, the contents of preβ1- HDL, HDL3b, and HDL3a were significantly higher than HDL2a and HDL2b in subjects in the middle and highest tertiles of the apoCII group. Moreover, regardless of whether apoB100 increased, preβ1-HDL contents increased, but HDL2b fell when apoCII rose while, at any apoCII levels, HDL2b rose with the elevation of apoA-I. Additionally, a reduction in preβ1-HDL (from 131.9 to 90.6 mg/L) but an increase in HDL2b (from 269.1 to 382.7 mg/L) with a rise in the apoCIII/CIi value (between 0.8 and 5.6) were also observed.
    Conclusion: The particle size of HDL become smaller with the increase of apoCII levels, implying that the efficiency of reverse cholesterol transport (RCT) was impaired and blocked the maturation of HDL. ApoCII might be an independent factor affecting the distribution of HDL subclasses. Further, the apoCIII/CII ratio correlated with the size of HDL particles.
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  • Yoh Miyashita, Atsuhito Saiki, Kei Endo, Noriko Ban, Takashi Yamaguchi ...
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 621-626
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: November 10, 2009
    JOURNALS FREE ACCESS
    Aim: Recently, a novel device for measuring the cardio-ankle vascular index (CAVI) as an arterial stiffness parameter has been developed. In this study, we evaluated the effect of angiotensin II receptor blocker (ARB) and calcium channel (Ca) blocker on CAVI in type 2 diabetic patients with hypertension.
    Methods: Seventy type 2 diabetes mellitus patients with hypertension were enrolled and randomly divided into two groups. One group was administered olmesartan medoxomil 10 mg/day for 12 months (ARB group), and the other group was administered amlodipine besilate 5 mg/day for 12 months (Ca blocker group).
    Results: In the ARB group, a significant decrease in CAVI was observed after 12 months; however, no significant change in CAVI was observed in the Ca blocker group although changes in blood pressure were almost the same. By simple regression analyses, CAVI changes correlated positively with 8-OHdG changes.
    Conclusions: Olmesartan, an ARB, improved arterial stiffness more than amlodipine, and this effect might be due to not only the blood pressure-lowering effect but also to reducing the potential of oxidative stress recognized in olmesartan.
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  • Liang-Kung Chen, Li-Ning Peng, Ming-Hsien Lin, Hsiu-Yun Lai, Shinn-Jan ...
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 627-632
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: November 10, 2009
    JOURNALS FREE ACCESS
    Aim: Metabolic syndrome (MS) has been shown to predict diabetes mellitus (DM) in previous studies, but little is known about older adults. The main purpose of this study is to evaluate whether MS predicts new onset diabetes (NOD) in older community-living Taiwanese.
    Methods: Community-living people aged over 40 who participated in annual health examinations held by community health clinics were invited to enrol in the study in 2000 and the status of DM was determined in 2005.
    Results: In total, 480 subjects (mean age: 63.7±10.8 years in year 2000, 43.8% males) were enrolled in this study. The prevalence of MS in 2000 was 25.4%. Overall, the 5-year cumulative incidence of NOD was 10.8%, and it was significantly higher in the MS group than non-MS group (17.2% vs. 8.7%, p=0.011). Adjusted for age and gender, MS significantly predicts NOD (OR: 2.20, 95% CI: 1.214.00, p=0.010). Moreover, both impaired fasting glucose (IFG) (OR: 4.48, 95% CI: 2.418.33, p<0.001) and hypertriglyceridemia (OR: 2.03, 95% CI: 1.043.94, p=0.037) significantly predicted NOD among all 5 diagnostic components. In terms of predicting NOD, IFG showed a higher positive predictive value than MS (42.9% vs. 17.2%).
    Conclusion: Both MS and IFG can effectively predict NOD among community-living older Taiwanese in 5-year follow-up; however, IFG alone may be a more efficient predictor of NOD because of a higher positive predictive value and lower laboratory cost.
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  • Rie Oka, Junji Kobayashi, Katsuyuki Miura, Shinya Nagasawa, Tadashi Mo ...
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 633-640
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: September 03, 2009
    JOURNALS FREE ACCESS
    Aim: Postprandial hypertriglyceridemia is recognized as an independent risk factor for cardiovascular disease. The aim of this study was to identify differences between fasting and postprandial TG levels, focusing on the influence of waist circumference.
    Methods: Subjects included 1,505 men and 798 women aged 3865 years who were not taking medications for diabetes or dyslipidemia. Fasting TG levels were measured after an overnight fast, and postprandial TG levels were measured 2 hours after a standardized rice-based lunch (total 740 kcal, 20 g fat, 30 g protein, and 110 g carbohydrates) in the afternoon on the same day.
    Results: Fasting and postprandial TG levels were highly correlated in both men (r=0.86, p<0.001) and women (r=0.84, p<0.001). Waist circumference was positively correlated with fasting TG (r=0.38 in men and r=0.36 in women) and postprandial TG (r=0.42 in men and r=0.45 in women), respectively. On multiple regression analyses, the association of waist circumference with postprandial TG was still significant (standardized β=0.10 in men and standardized β=0.15 in women, p<0.001) after the inclusion of HbA1c, age, high-density-lipoprotein (HDL)-cholesterol, alcohol consumption, and fasting TG in the regression model.
    Conclusion: Postprandial TG has a better relation with waist circumference than fasting TG.
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  • Jiang-jiao Xie, Xian Yu, Yu-hua Liao, Jian Chen, Rui Yao, Yong Chen, M ...
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 641-653
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: September 24, 2009
    JOURNALS FREE ACCESS
    Aim: Hyperhomocysteinemia (Hhcy) is an important and independent risk factor for atherosclerosis. Recent studies have shown that Poly (ADP-ribose) polymerase (PARP) activation may be associated with Hhcy-induced endothelial dysfunction, which is an important mechanism for Hhcy to affect atherosclerotic progress. Thus, we investigated whether PARP inhibitors may attenuate atheroscle-rotic plaque development in an Hhcy-induced experimental animal model with atherosclerosis.
    Methods: Six-week-old homozygous apolipoprotein E-deficient (ApoE-/-) male mice fed a normal diet or high methionine diet randomly received intraperitoneal injections of 10 mg/kg 3-aminoben-zamide (3-AB, a PARP inhibitor) dissolved in phosphate-buffered saline (PBS), or physiological saline every other day for 12 weeks. Atherosclerotic lesion sizes and PARP activity were measured. Related inflammatory factors in atherogenesis were investigated by real-time quantitative PCR and Western blot analysis.
    Results: Our data demonstrated that ApoE-/- mice fed a high methionine diet generated Hhcy, which subsequently increased the atherosclerotic lesion size significantly, promoted oxidative stress-associated DNA damage and PARP activation, then increased the expression of proinflammatory fac-tors within atherosclerotic plaques. Although PARP inhibition by 3-AB did not markedly inhibit plaque development in ApoE-/- mice with spontaneous hyperlipidemia by feeding a normal diet, it significantly reduced the atherosclerotic lesion size by 40% in Hhcy-induced atherosclerosis without affecting plasma homocysteine levels and lipid contents, effectively suppressed PARP activation, and inhibited nuclear translocation of nuclear factor-κB (NF-κB) and subsequent production of inflam-matory factors, such as vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattactant protein-1 (MCP-1).
    Conclusion: Our results suggest that PARP inhibition attenuates atherosclerotic plaque development under hyperhomocysteinemic conditions, through the inhibition of PARP activation, nuclear NF-κB translocation and subsequent expression of inflammatory factors.
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  • Tamio Teramoto, Hitoshi Shimano, Koutaro Yokote, Mitsuyoshi Urashima
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 654-661
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: November 10, 2009
    JOURNALS FREE ACCESS
    Background: Low high-density lipoprotein cholesterol (HDL-C) is an important clinical risk factor for cardiovascular disease (CVD). Statins have been known to have a potent HDL-C-elevating effect in addition to low-density lipoprotein cholesterol (LDL-C)-lowering effects.
    Methods: The database of LIVALO effectiveness and safety (LIVES) Study, a large-scale (n=20,279), long-term (104 weeks), prospective post-marketing surveillance of hypercholesterolemic patients treated with pitavastatin, was used to evaluate and analyze effects on plasma lipids, especially focusing on HDL-C.
    Results: Total cholesterol (TC) (-21.0%) and LDL-C (-31.3%) were significantly reduced. The decrease in triglyceride (TG) was significant in hypertriglyceridemic patients. HDL-C was elevated by 5.9% and 24.6% in all and in patients with low HDL-C levels (less than 40 mg/dL) at baseline, respectively (p<0.0001). In time-course analysis, elevation of HDL-C in the low HDL-C group was enhanced by 14.0% and 24.9% at 12 weeks and 104 weeks, respectively. A significant increase in HDL-C by pitavastatin treatment was also observed after switching from other statins. Multivariable analysis showed that BMI, diabetes, liver disease, and pre-treated other cholesterol-lowering drugs emerged as significant factors influencing HDL-C.
    Conclusions: Pitavastatin had stable clinical effects on LDL-C, TG, and HDL-C for 104 weeks. It was noteworthy that HDL-C in patients with low HDL-C was continuously increased by this agent during the period tested.
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  • Toshio Yamagishi, Makoto Kato, Yoshiro Koiwa, Ken Omata, Hideyuki Hase ...
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 662-673
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: November 10, 2009
    JOURNALS FREE ACCESS
    Aim: As an approach to tissue characterization, we attempted to classify in vivo carotid plaque tissues in terms of arterial wall elasticity instead of echogenicity on B-mode scanning and investigated whether the effect of fluvastatin on carotid elasticity can be detected in hypercholesterolemic patients. Methods: In 170 subjects, simultaneous measurements of intima-media thickness (IMT) and elastic modulus in the circumferential direction (Eθ) were performed using a new transcutaneous high-resolution Doppler technique.
    Results: From the observation of various tissues, an elasticity library was obtained as follows: lipid core, 22±15 kPa; calcification, 674±384 kPa; lipid core- and calcification-free plaques, 173±69 kPa; smooth muscle, 104±32 kPa; blood clot, 85±68 kPa; fibrosis, 273±173 kPa.
    The effect of fluvastatin (30 mg/day, n=62) was assessed over 12 months using the elasticity distribution and serum markers. The statin reduced low-density lipoprotein cholesterol, high-sensitivity CRP, mean IMT and mean Eθ, and increased nitrite/nitrate. In the max IMT ≥1.1 mm group, both Eθ and IMT decreased significantly. On the other hand, in the max IMT <1.1 mm group, Eθ but not IMT decreased significantly. The histogram of the subgroups showing increased Eθ with max IMT≥1.1 mm revealed a decrease in areas corresponding to Eθ of 20200 kPa (lipid/smooth muscle-rich tissue) and an increase in relatively hardened areas of <250 kPa (collagen fibers).
    Conclusion: Non-invasive echographic carotid arterial elasticity measurement is useful for the classification of atherosclerotic plaques and evaluation of chronological and histopathological changes.
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  • Takeshi Arai, Hyoun-ju Kim, Hiroshige Chiba, Akiyo Matsumoto
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 674-683
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: November 10, 2009
    JOURNALS FREE ACCESS
    Aim: The aim of our study is to elucidate the effects of EPA- or DHA-rich fish oil, and of the latter plus fenofibrate, on lipid metabolism in female KK mice.
    Methods: Female KK mice were fed purified experimental diets containing lard/safflower oil (4:6, Lard/SO), EPA-rich fish oil (EPA), DHA-rich fish oil (DHA), or DHA-rich fish oil plus 0.2% (w/w) fenofibrate (DHA+FF) for 8 weeks. At the end of the experiments, we measured levels of plasma lipids, hepatic triglycerides, and cholesterol, as well as the hepatic mRNA expression of lipogenic and lipidolytic genes.
    Results: The final body weight of EPA- and DHA-fed groups was significantly lower than that of the Lard/SO-fed group, and that of the DHA+FF-fed group was the lowest. All three fish oil treatments significantly reduced plasma insulin levels. Hepatic lipid levels significantly decreased in all three of these groups compared with the Lard/SO-fed group. Plasma adiponectin increased in both the EPA-and DHA-fed groups, but the increase was suppressed in the DHA+FF-fed group. Hepatocytes of Lard/SO-fed mice were filled with numerous fat droplets, but fat accumulation was inhibited in both EPA- and DHA-fed mice and was significantly prevented by fenofibrate treatment. SREBP-1c mRNA levels were decreased by about half in EPA- and DHA-fed mice compared with Lard/SO-fed mice. FAS, Insig-1, HMG-CoA reductase, and LDL-receptor mRNA levels also markedly decreased in both EPA- and DHA-fed mice, but there was no additional decrease in DHA+FF fed mice. Fenofibrate treatment significantly induced mRNA expression of AOX and UCP-2, but not of PPARα.
    Conclusion: These data suggest that fish oil inhibited body weight gain and exhibited an anti-obesity effect through the inhibition of lipid synthesis in female KK mice. Furthermore, fenofibrate treatment markedly inhibited body weight gain by the induction of fatty acid oxidation. Plasma adiponectin levels did not increase in mice fed DHA-rich fish oil with fenofibrate, although white adipose tissue (WAT) weight significantly decreased. We considered that adiponectin sensitivity increased more in mice fed DHA-rich fish oil with fenofibrate than in mice fed DHA-rich fish oil alone.
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  • Muzeyyen Aslan Bahadir, Aytekin Oguz, Mehmet Uzunlulu, Ozgur Bahadir
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 684-690
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: September 14, 2009
    JOURNALS FREE ACCESS
    Aim: To compare the effects of different low-density lipoprotein (LDL) cholesterol-lowering statin treatments on small dense LDL (sd-LDL) in hypercholesterolemic patients with metabolic syndrome (MetS).
    Methods: Forty hypercholesterolemic MetS patients ?30 years of age were randomized to rosuvas-tatin (n=17) or other statins (n=23) groups. In the other statins group, those taking atorvastatin (n=12) were also evaluated separately. Statin doses were 10 mg/day rosuvastatin, 20 mg/day atorvas-tatin, 40 mg/day simvastatin, and 40 mg/day pravastatin. Treatment duration was planned to be 8 weeks. Sd-LDL levels were assessed at baseline and at the completion of treatment.
    Results: After treatment, sd-LDL levels were significantly reduced in all 3 groups (from 29.6±24.8 mg/dL to 8.9±8.5 mg/dL in the rosuvastatin group, p=0.001; from 26.2±15 mg/dL to 14.8±9.6 mg/dL in the atorvastatin group, p=0.02; and from 29.1±16.5 mg/dL to 14.7±11.2 mg/dL in the other statins group, p=0.0001). There was no significant difference in the mean percent changes among groups.
    Conclusion: Significant reduction in sd-LDL levels was observed after 8 weeks of statin treatment in hypercholesterolemic patients with MetS. This effect was similar for all statins and can be considered a class effect.
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  • Takehiro Torisu, Yutaka Takata, Toshihiro Ansai, Takayuki Matsumoto, K ...
    Type: Original Article
    2009 Volume 16 Issue 5 Pages 691-697
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: September 03, 2009
    JOURNALS FREE ACCESS
    Aim: Helicobacter pylori (HP) has been implicated as a risk factor for cardiovascular and atherosclerotic diseases. Arterial stiffness determined by pulse wave velocity (PWV) or the cardio-ankle vascular index (CAVI) has been shown to be higher in HP-positive subjects than in HP-negative subjects; however, this result has been observed only in young subjects. The aim of the study was to investigate the possible correlation between HP infection and PWV or CAVI in middle-aged subjects.
    Methods: We measured brachial-ankle PWV (baPWV), CAVI, metabolism markers, pepsinogens (PGs) and IgG antibody to HP in 343 individuals aged either 60 or 65 year old. Atrophic gastritis (AG) was diagnosed based on the values of PGs.
    Results: baPWV and CAVI were significantly higher in the AG-positive group than in the AG-negative group even after adjusting for possible confounding factors (baPWVc; 16.63±3.50 vs. 15.59±3.47 p=0.010, CAVIc; 8.59±1.20 vs. 8.27±1.19 p=0.022). baPWV and CAVI values tended to be higher in the HP-positive group than in the HP-negative group. High-density lipoprotein (HDL) cholesterol level and the adiponectin level were lower in the AG-positive group than in the AG-negative group.
    Conclusion: There may be an association between atrophic gastritis and atherosclerosis in middle-aged subjects.
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Case Report
  • Tadashi Ohshiro, Tadao Shimabukuro, Makoto Sunagawa, Takao Ohta
    Type: Case Report
    2009 Volume 16 Issue 5 Pages 698-701
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: August 27, 2009
    JOURNALS FREE ACCESS
    Familial hypercholesterolemia (FH) is characterized by a high level of LDL-cholesterol (LDL-C) and a high prevalence of atherosclerotic coronary heart disease; however, hypercholesterolemia is usually the only clinical finding in children with heterozygous FH in their first decade of life. We report a case of FH in an 11-year-old boy who presented with multiple xanthomas at both elbows, thickened Achilles tendons, and hyperplasia of the intima-media complex of the carotid artery. Echocardiogram revealed partial calcification of the aortic and mitral valves, but no stenosis of the coronary arteries was detected on 3D-computed tomography. The activity of LDL receptors was reduced to 32% by lymphocyte assay. The family history showed vertical transmission of hypercholesterolemia from father to son, thereby suggesting dominant inheritance. After 12 months of treatment with statin and resin, his LDL-C decreased from 446 to 220 mg/dL, thickening of the Achilles tendons decreased from 1618 mm to 13 mm, and hyperplasia of the intima-media complex decreased from 1.3 mm to 0.7 mm. These findings suggest that our patient had heterozygous FH. However, based on his advanced atherosclerosis, we cannot exclude the possibility that our patient may be accompanying dyslipidemia due to causes in addition to heterozygous FH.
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Communication
  • Ken-ichi Hirano
    Type: Communication
    2009 Volume 16 Issue 5 Pages 702-705
    Published: 2009
    Released: November 11, 2009
    [Advance publication] Released: September 03, 2009
    JOURNALS FREE ACCESS
    Heart diseases, including atherosclerotic cardiovascular disease and congestive heart failure, are major life-threatening disorders in most countries. Cholesterol is a vital causal factor and focus of research into heart diseases, but the involvement of triglycerides remains unclear. We recently reported a unique patient suffering from severe congestive heart failure and needing cardiac transplantation. Massive accumulation of triglycerides was observed in coronary atherosclerotic lesions as well as in the myocardium, while plasma triglyceride levels were normal. We suggested that this phenotype was a novel clinical entity and named it “Triglyceride deposit cardiomyovasculopathy”, or simply “Obesity of the heart”. The patient was identified as homozygous for a genetic mutation in the adipose triglyceride lipase, an essential molecule for hydrolysis of intracellular triglycerides. The present paper deals with what we can learn from this single case and discusses its implications for research and clinical medicine related to heart diseases.
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