Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Volume 18 , Issue 8
Showing 1-12 articles out of 12 articles from the selected issue
Review
  • Yuji Matsuzawa, Tohru Funahashi, Tadashi Nakamura
    Type: Review
    2011 Volume 18 Issue 8 Pages 629-639
    Published: 2011
    Released: August 24, 2011
    [Advance publication] Released: July 08, 2011
    JOURNALS FREE ACCESS
    Although abdominal obesity or visceral obesity is considered to be one of the components of metabolic syndrome and to have an important role in a cluster of cardiovascular risks, there is no consensus about the definition and diagnostic criteria for this syndrome, probably because there is considerable disagreement about the location and definition of abdominal obesity or visceral obesity.
    In this review article, the important role of visceral fat accumulation in the development of a variety of lifestyle-related diseases is shown, including cardiovascular disease based on our clinical studies using CT scans, and the mechanism of these disorders is discussed, focusing on adipocytokines, especially adiponectin.
    The importance of diagnosing metabolic syndrome, in which visceral fat accumulation plays an essential role in the development of multiple risk factors, should be emphasized because lifestyle modification for the reduction of visceral fat may be very effective for the reduction of risks of this type, namely metabolic syndrome in the narrow sense.
    Download PDF (1440K)
Original Article
  • Álvaro Cerda, Fabiana Dalla Vecchia Genvigir, Alice Cristina Ro ...
    Type: Original Article
    2011 Volume 18 Issue 8 Pages 640-651
    Published: 2011
    Released: August 24, 2011
    [Advance publication] Released: April 21, 2011
    JOURNALS FREE ACCESS
    Aim: This study evaluated the influence of polymorphisms and cholesterol-lowering treatments on SCARB1 mRNA expression in peripheral blood mononuclear cells and in HepG2 and Caco-2 cells.
    Methods: Blood samples were drawn from normolipidemic (NL, n=166) and hypercholesterolemic (HC, n=123) individuals to extract DNA and total RNA and to analyze the lipid profile. After a 4-week washout period, 98 HC individuals were treated with atorvastatin (10 mg/day/4 weeks) whereas 25 were treated with ezetimibe (10 mg/day/4 weeks), followed by simvastatin (10 mg/day/8 weeks) and simvastatin plus ezetimibe (10 mg each/day/4 weeks). HepG2 and Caco-2 cells were treated with atorvastatin, simvastatin and ezetimibe at various concentrations for 12 and 24 h and collected for RNA extraction. SCARB1 mRNA expression was measured by TaqMan® assay and SCARB1 c.4G> A, c.726+54C> T and c.1080C> T polymorphisms were detected by PCR-RFLP.
    Results: High LDL cholesterol (> 160 mg/dL) values were associated with low baseline SCARB1 mRNA expression in PBMC. Allele T carriers for SCARB1 c.726+54C> T had lower basal SCARB1 transcription in PBMC (p < 0.05). Simvastatin, atorvastatin and ezetimibe treatments did not modify the SCARB1 mRNA level in PBMC from HC patients. Similarly, these cholesterol-lowering drugs did not modulate the SCARB1 expression in HepG2 and Caco-2 cells in spite of the concentration and time of exposure (p > 0.05).
    Conclusion: LDL cholesterol levels and SCARB1 c.726+54C> T are associated with low mRNA expression in mononuclear cells. Cholesterol-lowering drugs do not modulate SCARB1 expression in PBMC from HC subjects or in HepG2 and Caco-2 cells.
    Download PDF (478K)
  • Chiu-Shong Liu, Chia-Ing Li, Chuen-Ming Shih, Wen-Yuan Lin, Chih-Hsueh ...
    Type: Original Article
    2011 Volume 18 Issue 8 Pages 652-658
    Published: 2011
    Released: August 24, 2011
    [Advance publication] Released: April 06, 2011
    JOURNALS FREE ACCESS
    Aim: Carotid-femoral pulse wave velocity is a well-known predictor of all-cause and cardiovascular mortality. Few studies have evaluated the relationship between brachial-ankle pulse wave velocity (ba-PWV) and coronary artery disease. We conducted this study to elucidate the relationship between arterial stiffness measured by ba-PWV and coronary atherosclerosis.
    Methods: An automatic waveform analyzer was used to measure the ba-PWV. Multidetector computed tomography coronary angiography was used to assess the coronary artery calcium (CAC) score and to detect coronary stenosis. A total of 654 patients, including 358 women and 296 men (mean age, 54.5±9.4 years), were recruited during the period March 2005 to June 2008.
    Results: One hundred and twenty-seven patients (19.4%) had at least one stenotic coronary vessel. Mean ba-PWV and mean CAC scores were significantly higher in the stenotic group than in the normal control (15.94±3.07 m/s vs. 14.39±0.98 m/s; 293.1±435.9 vs. 29.8±110.8, respectively; both p < 0.001). The adjusted OR for coronary stenosis increased as ba-PWV increased (p for trend=0.0001). Using ba-PWV < 14.0 m/s as the reference group, we found that ba-PWV between 14.0-18.0 m/s and ba-PWV > 18.0 m/s were significantly associated with coronary stenosis (OR, 2.48; CI, 1.56-3.93 and OR, 3.16; CI, 1.68-5.95, respectively). The cutoff point at 15.64 m/s using the ROC curve showed a sensitivity of 64.5%, specificity of 65.6%, and an AUC of 0.662 in predicting coronary artery stenosis. Ba-PWV had an additional power for correlating coronary artery disease with the Framingham risk score.
    Conclusions: Ba-PWV correlated well with coronary atherosclerosis. Lifestyle modification is an efficacious therapeutic intervention for preventing the progression of arterial stiffness. This non-invasive technique can assist in the early detection of cardiovascular disease and should be included in community screening programs.
    Download PDF (200K)
  • Eun-Seok Park, Yong Lim, Seung-Ho Lee, Byoung-Mog Kwon, Hwan-Soo Yoo, ...
    Type: Original Article
    2011 Volume 18 Issue 8 Pages 659-669
    Published: 2011
    Released: August 24, 2011
    [Advance publication] Released: April 21, 2011
    JOURNALS FREE ACCESS
    Aim: Thrombosis occurs in the coronary arteries via the activation of platelets, and leads to acute myocardial infarction and sudden death. Obovatol, a major biphenolic component of Magnolia Obovata leaves, displays anti-inflammatory and acyl Co-A cholesterol acyltrasferase inhibitory effects. The purpose of this study was to determine the effects of obovatol on thrombus formation in vivo and platelet activation in vitro and ex vivo.
    Methods: We investigated the antiplatelet and antithrombotic activities of obovatol in rat carotid arterial thrombosis in vivo along with platelet aggregation in vitro and ex vivo. Its possible cellular mechanism of antiplatelet activity was investigated by testing PLC-γ2 activation, arachidonic acid cascade, calcium mobilization and granule secretion.
    Results: Oral administration of obovatol prevented carotid thrombosis, but also significantly inhibited collagen-induced platelet aggregation. Obovatol did not change coagulation times, such as activated partial thromboplastin time and prothrombin time, indicating that the antithrombotic effect of obovatol might be due to antiplatelet activity rather than anticoagulation activity. Obovatol inhibited in vitro collagen- and arachidonic acid-induced rabbit platelet aggregation in a concentration-dependent manner (1-10 µM), with IC50 values of 2.4±0.8 and 4.8±0.9 µM, respectively. Obovatol blocked collagen-mediated phospholipase C-γ2 phosphorylation, cytoplasmic calcium mobilization, arachidonic acid liberation and serotonin secretion.
    Conclusion: Obovatol has a potent antithrombotic effect, which may be due to antiplatelet activity. The antiplatelet activity of obovatol is mediated by inhibition of PLC-γ2 phosphorylation. Thus, obovatol may be a potential candidate to treat cardiovascular disease.
    Download PDF (1815K)
  • Toshihiro Suga, Tatsuya Iso, Takehisa Shimizu, Toru Tanaka, Sho-ichi Y ...
    Type: Original Article
    2011 Volume 18 Issue 8 Pages 670-683
    Published: 2011
    Released: August 24, 2011
    [Advance publication] Released: April 21, 2011
    JOURNALS FREE ACCESS
    Aim: Vascular calcification is prevalent in patients with diabetes and chronic kidney disease. Receptor for advanced glycation end products (RAGE) and its multiple ligands have been implicated in the pathogenesis of accelerated atherosclerosis; however, little is known about the effects of RAGE activation on vascular calcification.
    Methods and Results: Cultured rat and human aortic smooth muscle cells (HASMC) were transduced with adenovirus expressing RAGE. Expression of myocardin and the SMC-marker genes was significantly repressed in these cells. RAGE activation inhibited myocardin-induced expression of the SMC genes in mouse embryonic mesenchymal C3H10T1/2 cells. Interestingly, RAGE activation induced alkaline phosphatase (ALP) expression, calcium deposition, and Msx2 expression, a crucial transcription factor for osteogenic differentiation, in HASMC. RAGE-induced osteogenic differentiation was significantly inhibited by endogenous secretory RAGE. RAGE-induced ALP and Msx2 expression was completely abrogated by DAPT, an inhibitor of the Notch signaling pathway. PD98059 (MEK inhibitor) effectively blunted RAGE-induced Notch1 and Msx2 gene expression. Simultaneous stimulation with bone morphogenetic protein 2 (BMP2) and RAGE signaling synergistically induced expressions of Msx2 and ALP in HASMC. Immunohistochemistry revealed that the human calcifying atherosclerotic plaque expressed RAGE, Notch components and Msx2. The ALP activity induced in RAGE-overexpressing HASMCs by human serum was positively correlated with the serum creatinine level, but not with phosphate and hemoglobin A1c levels.
    Conclusions: These results indicate that activation of RAGE not only inhibits myocardin-dependent SMC gene expression, but also induces osteogenic differentiation of vascular SMC through Notch/Msx2 induction. These results provide a novel insight into the role of RAGE axis in vascular calcification.
    Download PDF (3622K)
  • Ichiro Wakabayashi
    Type: Original Article
    2011 Volume 18 Issue 8 Pages 684-692
    Published: 2011
    Released: August 24, 2011
    [Advance publication] Released: May 12, 2011
    JOURNALS FREE ACCESS
    Aim: Results of previous studies on the relationship between habitual alcohol drinking and metabolic syndrome in a general population are not consistent, and this relationship in patients with diabetes is unknown. The aim of this study was to clarify the relationship of alcohol consumption with meta-bolic syndrome in patients with diabetes.
    Methods: Japanese male workers with diabetes (n = 1960) were divided into non-, light (< 22 g ethanol/day), heavy (≥ 22 and < 44 g ethanol/day) and very heavy (≥ 44 g ethanol/day) drinkers. Re-lationships of alcohol consumption with visceral obesity evaluated by waist circumference, high blood pressure, dyslipidemia (high triglycerides and/or low HDL cholesterol), hyperglycemia, and metabolic syndrome (3 or more of these risk factors by the NCEP-ATP III criteria) were investigated.
    Results: Odds ratio vs. nondrinkers for high blood pressure was significantly high in all drinker groups, while odds ratio vs. nondrinkers for low HDL cholesterol was significantly low in all drinker groups. Odds ratio vs. nondrinkers for high triglycerides was significantly low in light drinkers and was significantly high in very heavy drinkers. Odds ratio vs. the nondrinker group for large waist circumference was not significant in any drinker groups. Odds ratio vs. nondrinkers for metabolic syndrome was significantly high in very heavy drinkers but was not significant in light and heavy drinkers.
    Conclusion: Excessive alcohol intake is associated with a higher risk for metabolic syndrome through elevations of blood pressure and triglycerides in Japanese male patients with diabetes.
    Download PDF (1185K)
  • Ahmet Celik
    Type: Original Article
    2011 Volume 18 Issue 8 Pages 693-697
    Published: 2011
    Released: August 24, 2011
    [Advance publication] Released: April 21, 2011
    JOURNALS FREE ACCESS
    Aim: The increase of tenascin-C levels after myocardial infarction has been demonstrated by previous studies. The relationship between tenascin-C and the grade of stenosis in the infarct-related coronary artery was indeterminate. The aim of this study was to evaluate the relationship between tenascin-C levels and total occlusion after acute myocardial infarction.
    Method: Fifty-nine patients with subacute anterior myocardial infarction were divided into two groups according to their having a totally or subtotally occluded left anterior desending artery. Plasma tenascin-C, troponin I, CK-MB, uric acid, mean platelet volume, and lipid profile levels were also measured.
    Results: The history of the smoking rate, hypertension and diabetes mellitus were similar in both groups. Hemoglobin, mean platelet volume, serum creatinine, CK-MB, troponin I, serum lipid profile and uric acid levels were similar in the two groups. The CRP and tenascin-C levels were significantly higher in the total occlusion group. Tenascin-C levels were highest in patients with proximal LAD total occlusion and lowest in patients with subtotal LAD occlusion. The tenascin-C levels were correlated with the grade of stenosis (r =0.602, p < 0.001).
    Conclusion: This study demonstrates that higher tenascin-C levels were related with the total occlusion and inflammation after MI.
    Download PDF (111K)
  • Mariko Tani, Akio Kawakami, Yuki Mizuno, Reina Imase, Yasuki Ito, Kazu ...
    Type: Original Article
    2011 Volume 18 Issue 8 Pages 698-704
    Published: 2011
    Released: August 24, 2011
    [Advance publication] Released: April 21, 2011
    JOURNALS FREE ACCESS
    Aim: Increased levels of small dense low-density lipoproteins (sd-LDL) have been reported more atherogenic compared to total low-density lipoprotein (LDL); however, no definitive experiments using macrophages have examined this concept in vitro.
    Method and Result: In this study, we isolated fractions of total LDL (density 1.019-1.063g/ml) and sd-LDL (density 1.044-1.063g/ml) from the plasma of subjects with modest hypertriglycidemia. Oxidizabilty as assessed by copper-induced generation (1.6 µmol/L CuSO4,12 h) of thiobarbituric acid reactive substances (TBARS) was significantly greater (7-fold higher, p < 0.01) for sd-LDL (4.3±1.1 nmol/mg) than for total LDL (0.6±0.2 nmol/mg) at the same cholesterol concentrations. Moreover, oxidized sd-LDL induced more lipid staining in macrophages than oxidized total LDL. When non-oxidized sd-LDL were incubated with THP1 macrophages, there was much greater lipid accumulation as assessed by oil red O staining, and more than a 2-fold increase (p < 0.05) in intracellular triglyceride content as compared to non-oxidized total LDL. Furthermore, non-oxidized sd-LDL in contrast to non-oxidized total LDL enhanced macrophage lectin-like oxidized LDL receptor-1 (LOX-1) protein expression and significantly LOX-1 mRNA levels (+158%, p < 0.05), with no effect on scavenger receptor A or CD36 gene expression. These effects of non-oxidized sd-LDL on LOX-1 gene expression were suppressed when Toll-like receptor 4 was inactivated either by RNAi or antibody.
    Conclusion: Our data indicate for the first time that sd-LDL is much more effective in promoting macrophage triglyceride accumulation and LOX-1 gene expression than total LDL.
    Download PDF (792K)
  • Tomoko Usui, Toshiharu Ninomiya, Masaharu Nagata, Yasufumi Doi, Jun Ha ...
    Type: Original Article
    Subject area: — The Hisayama Study
    2011 Volume 18 Issue 8 Pages 705-712
    Published: 2011
    Released: August 24, 2011
    [Advance publication] Released: May 02, 2011
    JOURNALS FREE ACCESS
    Aims: To elucidate the relationship between albuminuria and the prevalence of peripheral arterial disease (PAD), and to examine the effect of albuminuria on the ability to assess the likelihood of PAD in a general Japanese population.
    Methods: In 3,061 community-dwelling subjects aged. 40 years, we investigated the association of urinary albumin-creatinine ratio (UACR) levels with the prevalence of PAD, defined as an ankle-brachial index < 0.9. The odds ratio for the presence of PAD was estimated using the logistic regression model. To compare the accuracy of the assessment for the likelihood of prevalent PAD between models adjusted for potential risk factors with and without UACR levels, the receiver operating characteristic (ROC) curves were plotted.
    Results: Overall, 1.47% of the study participants had PAD. The age- and sex-adjusted prevalence of PAD increased linearly for UACR levels of < 5.6, 5.6-10.8, 10.9-29.9, 30.0-300.0, and >300.0 mg/g, being 0.34, 0.80, 2.02, 2.50, and 2.53%, respectively (p for trend <0.001). The multivariate-adjusted odds ratio for the presence of PAD was 1.85 (95% confidence interval 1.12-3.06) for every 10-fold increment in UACR. The area under the ROC curve significantly increased when UACR levels were incorporated into a model with potential risk factors for PAD (0.80 vs. 0.77, p= 0.02).
    Conclusion: Greater UACR levels are associated linearly with a higher prevalence of PAD, even within the normoalbuminuric range, in the general Japanese population, and combining UACR levels with potential risk factors substantially improves the performance to assess the likelihood of PAD.
    Download PDF (360K)
Case Report
  • Xiao Li Wang, Jun-ichi Osuga, Fumiko Tazoe, Kenta Okada, Shuichi Nagas ...
    Type: Case Report
    2011 Volume 18 Issue 8 Pages 713-719
    Published: 2011
    Released: August 24, 2011
    [Advance publication] Released: May 20, 2011
    JOURNALS FREE ACCESS
    Lecithin-cholesterol acyltransferase (LCAT) is an important enzyme involved in the esterification of cholesterol. Here, we report a novel point mutation in the LCAT gene of a 63-year-old female with characteristics of classic familial LCAT deficiency. The patient's clinical manifestations included corneal opacity, mild anemia, mild proteinuria and normal renal function. She had no sign of coronary heart disease. Her LCAT activity was extremely low. DNA sequencing revealed a point mutation in exon 5 of the LCAT gene: a G to C substitution converting Gly179 to an Arg, located in one of the catalytic triads of the enzyme. In vitro expression of recombinant LCAT proteins in HEK293 cells showed that the mutant G179R protein was present in the cell lysate, but not the culture medium. LCAT activity was barely detectable in the cell lysate or medium of the cells expressing the G179R mutant. This novel missense mutation seems to cause a complete loss of catalytic activity of LCAT, which is also defective in secretion.
    Download PDF (324K)
Letter to Editor
Correspondence
feedback
Top