Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Volume 9 , Issue 1
Showing 1-9 articles out of 9 articles from the selected issue
Review
  • Yoshiya Hata, Hiroshi Mabuchi, Yasushi Saito, Hiroshige Itakura, Gensh ...
    Type: Others
    Subject area: Others
    2002 Volume 9 Issue 1 Pages 1-27
    Published: 2002
    Released: October 31, 2003
    JOURNALS FREE ACCESS
    This paper described the Guideline for Diagnosis and Management of Hyperlipidemias for Prevention of Atherosclerosis proposed by The Japan Atherosclerosis Society (JAS) Guideline Investigating Committee (1, 995-2, 000) under the auspices of the JAS Board of Directors.
    1) The guideline defines the diagnostic criteria for serum total cholesterol (Table 1), LDL-cholesterol (Table 1), triglycerides (Table 4) and HDL-cholesterol (Table 7). It also indicates the desirable range (Table 1), the initiation levels of management (Table 2) and the target levels of treatment (Table 2) for total and LDL-cholesterol.
    2) Though both total and LDL-cholesterol are shown as atherogenic parameter in the guideline, the use of LDL-cholesterol, rather than total cholesterol, is encouraged in daily medical practice and lipid-related studies, because LDL-cholesterol is more closely related to atherosclerosis.
    3) Elevated triglycerides and low HDL-cholesterol are included in the risk factors, since no sufficient data have been accumulated to formulate the guideline for these two lipid disorders.
    4) Emphasis is laid on evaluation of risk factors of each subject before starting any kind of treatment (Table 2).
    5) This guideline is applied solely for adults (age 20-64). Lipid abnormalities in children or the youth under age 19, and the elderly with an age over 65 have to be evaluated by their own standard.
    6) This part of the guideline gives only the diagnostic aspects of hyperlipidemias. The part of management and treatment will follow in the second section of the guideline that will be published in future.
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Original Articles
  • Miyao Matsubara, Hitoshi Chiba, Shoji Maruoka, Shinji Katayose
    Type: Others
    Subject area: Others
    2002 Volume 9 Issue 1 Pages 28-34
    Published: 2002
    Released: October 31, 2003
    JOURNALS FREE ACCESS
    The serum uric acid level has been said to be an independent predictor of cardiovascular disease death, mainly for women, and to be linked with the metabolic Syndrome X of insulin resistance, obesity, hypertension, and dyslipidemia. Recently, it has been suggested that the elevation of serum leptin, the ob gene product, may have a role in metabolic Syndrome X. Therefore, we studied the relationship of uric acid to leptin in 822 Japanese women in a cross-sectional manner. To estimate the effect of uric acid on the variables of metabolic Syndrome X, we calculated mean values of various components of the syndrome according to tertiles of uric acid (UA<4.0 mg/dl, 4.0≤UA<5.5, 5.5≤UA). Age, systolic and diastolic blood pressure (BP), body mass index (BMI), percent body fat mass (BFM), serum total cholesterol, triglyceride, atherogenic index, leptin, fasting immunoreactive insulin and homeostasis model assessment-ratio (HOMA-R: calculated insulin resistance) were significantly different across the uric acid tertiles with higher levels in the highest tertile in comparison to the first (ANOVA, p<0.001, 0.001, 0.002, 0.001, 0.001, 0.025, 0.001, 0.001, 0.001, 0.001, 0.001, respectively), while high density lipoprotein cholesterol showed lower levels (p<0.001). Serum leptin concentrations were also elevated in hyperuricemic women after adjusting for BMI or BFM (both p<0.001), and were weakly correlated with serum uric acid concentrations (r=0.22, p<0.0001). BMI, HOMA-R, serum triglyceride, diastolic BP and age-adjusted serum leptin concentrations were calculated for each tertile of serum uric acid. Compared with the lowest tertile of uric acid level, BMI, HOMA-R, serum triglyceride, diastolic BP and age-adjusted leptin concentrations were higher in the highest tertile. In the stepwise regression analysis, serum leptin was the significant independent variable for uric acid values. These results indicate an independent relationship between leptin and uric acid, further supporting the involvement of leptin in metabolic Syndrome X.
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  • Osamu Tokunaga, Toshimi Satoh, Shi Yu
    Type: Others
    Subject area: Others
    2002 Volume 9 Issue 1 Pages 35-41
    Published: 2002
    Released: October 31, 2003
    JOURNALS FREE ACCESS
    The existence of large endothelial cells in the human aorta, especially on atherosclerotic lesions has been reported. They have multiple nuclei and are called “multinucleated variant endothelial cells (MVECs)”. In the present study caveolin expression was demonstrated in both MVECs and small typical endothelial cells (TECs). Caveolin was expressed diffusely as fine particles, and caveoles were expressed as prominent accumulations of caveolin in the cytoplasm. LDL was bound to the endothelial surface. With double immunostaining for caveolin and LDL, the location of LDL corresponded to the immunoreactive caveoles. Over time, large dots of LDL appeared in MVECs, whereas a few fine particles remained in TECs. An electron microscopic chase study of LDL-gold uptake identified many LDL-gold particles in plasmalemmal vesicles and in endosomes or lysosomes of MVECs, but only a few particles were found in TECs. Gold containing vesicles often were located near the abluminal surface. The number of LDL-gold particles was 4.5 times greater per unit area in MVECs than in TECs. Some of the gold particles were located in the subendothelial collagen matrix. These findings indicate that MVECs have a greater capacity of LDL cholesterol uptake followed by transport to the subendothelial matrices than TECs, and that MVECs contribute to the development and advancement of atherosclerotic lesions.
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  • Kazuhiro Ogura, Takashi Miyatake, On Fukui, Takafumi Nakamura, Takashi ...
    Type: Others
    Subject area: Others
    2002 Volume 9 Issue 1 Pages 42-47
    Published: 2002
    Released: October 31, 2003
    JOURNALS FREE ACCESS
    We investigated the changes of low-density lipoprotein (LDL) size and serum lipids during pregnancy and postpartum not only in normal pregnant women but also in preeclampsia. Serum triglyceride (TG) and total cholesterol levels as well as serum high-density lipoprotein (HDL)-cholesterol, apolipoprotein (Apo) A1, B, E and remnant-like particle (RLP)-cholesterol levels were increased in normal pregnant women. The LDL peak particle diameter (PPD) in normal pregnant women was decreased during pregnancy and that at 37 weeks of gestation showed significant decrease compared with the women at 4 weeks after delivery (25.8±1.0 vs. 26.8±0.7 nm, p<0.05). The LDL-PPD in the preeclamptic women at admission (mean gestational age: 36±2.4 weeks) was significantly lower than that in normal pregnancy at 37 weeks of gestation (24.7±1.2 vs. 25.8±1.0 nm, p<0.05). Moreover, the LDL-PPD in the preeclamptic women was significantly higher after delivery compared with the level at admission (27.5±0.7 vs. 24.7±1.2 nm, p<0.05) accompanied by an improvement in plasma lipids profile. These findings suggest that the predominance of small, dense LDL, a potential contributor to endothelial dysfunction, may be a possible predictor of preeclampsia.
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  • Akira Yamamoto, Kikuo Arakawa, Jun Sasaki, Yuji Matsuzawa, Kaoru Takem ...
    Type: Others
    Subject area: Others
    2002 Volume 9 Issue 1 Pages 48-56
    Published: 2002
    Released: October 31, 2003
    JOURNALS FREE ACCESS
    The effects and tolerability of the new HMG-CoA reductase inhibitor rosuvastatin were assessed in 68 hypercholesterolemic Japanese patients (22 men and 46 postmenopausal women; age range 28-72 years) in a multicenter, double-blind, dose-ranging, early phase II study. Patients were randomized into three groups and received once-daily doses of 1, 2, or 4 mg rosuvastatin. Sixty evaluable patients (19 men and 41 women) with mean total cholesterol (TC) 294 mg/dl (7.60 mmol/l) and mean triglyceride (TG) 150 mg/dl (1.69mmol/l) provided data in the efficacy analysis based on percentage changes in lipids at 4 and 8 weeks. All doses of rosuvastatin improved lipid parameters after both 4 and 8 weeks of therapy. On average, TC decreases were 22-29%, low-density lipoprotein cholesterol (LDL-C) decreases 32-42%, TG decreases 2% to 22%, and HDL-C increases 3-7%. There were no remarkable differences between efficacy at 4 and at 8 weeks, and dose-dependent reductions were noted for LDL-C, with 30, 39, and 42% decreases in the 1-, 2-, and 4-mg/day dose groups, respectively, at 8 weeks. The drug was well tolerated over the 8 weeks of therapy. These preliminary results indicate that rosuvastatin is a potent cholesterol-lowering agent, capable of achieving marked reductions in LDL-C even at low doses.
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  • Kayo Tsukamoto, Makoto Kinoshita, Kyoko Kojima, Yoko Mikuni, Mikiko Ku ...
    Type: Others
    Subject area: Others
    2002 Volume 9 Issue 1 Pages 57-64
    Published: 2002
    Released: October 31, 2003
    JOURNALS FREE ACCESS
    Several species of scavenger receptors have so far been identified. However, it remains unclear which receptors are more crucial for the foam cell formation and progression. In the present study, we compared five major scavenger receptors (SR-A, CD36, CLA-1, CD68, and LOX-1) in their levels of expression at the different stages of foam cells derived from THP-1 cells. The expression of all scavenger receptors examined was up-regulated by the stimulation with TPA for 48 hours, despite the expressions of SR-A, CD36 and LOX-1 being very low before the treatment with TPA. Four to 7 days after the removal of TPA, the levels of CD36, CLA-1 and CD68 were increased significantly. In contrast, the expression of SR-A was suppressed significantly, and no change was observed in that of LOX-1. Furthermore, when the transformed macrophages were incubated with oxidized LDL, in which the uptake of [3H] cholesteryl oleoyl ether-labeled OxLDL was linear up to 7 days after the addition of OxLDL, the expression of CD36, CLA-1 and CD68 were greatly enhanced. This enhancement was more prominent than that without oxidized LDL, and the enhancement was sustained throughout the experimental period. On the other hand, SR-A was not up-regulated, and LOX-1 was down-regulated. We thus propose that CD36, CLA-1 and CD68, but not SR-A and LOX-1, may play crucial roles in the progression of macrophages to foam cells, which is a key step for the initiation of atherosclerosis.
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  • Yoh Miyashita, Hiroshi Ozaki, Nobukiyo Koide, Masaki Otsuka, Tomokazu ...
    Type: Others
    Subject area: Others
    2002 Volume 9 Issue 1 Pages 65-71
    Published: 2002
    Released: October 31, 2003
    JOURNALS FREE ACCESS
    We investigated the mechanism by which 7-ketocholesterol damages vascular smooth muscle cells and the protective effect of the hydroxymethyl glutary CoA reductase inhibitor, pravastatin on it. When 7-ketocholesterol (50 μmol/L) was added to cultured human vascular smooth muscle cells, the extent of cell detachment increased and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling was positive. DNA extracted from the smooth muscle cells exposed to 7-ketocholesterol showed a ladder pattern on agarose electrophoresis. The fragmented DNA also increased in smooth muscle cells incubated with 7-ketocholesterol dose-dependently. In the presence of pravastatin, the cell detachment induced by 7-ketocholesterol was inhibited and the amount of fragmented DNA decreased significantly. These effects of pravastatin were inhibited by mevalonate. The results suggest that 7-ketocholesterol-induced apoptosis of vascular smooth muscle cells is inhibited by pravastatin, and mevalonate acts as a trigger of the apoptosis.
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  • Eriko Morishita, Shinji Minami, Chizuko Ishino, Masanori Kanno, Chika ...
    Type: Others
    Subject area: Others
    2002 Volume 9 Issue 1 Pages 72-77
    Published: 2002
    Released: October 31, 2003
    JOURNALS FREE ACCESS
    Atorvastatin is a powerful new synthetic 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor currently in clinical use. Its effects on plasma levels of factor VII were examined in 30 hyperlipidemic patients. After 12 weeks of atorvastatin treatment, factor VII activity (FVIIc) and factor VII antigen (FVIIag) levels had decreased by 13% (p<0.0001) and 12% (p<0.0001), respectively. The decreased concentrations of serum triglycerides correlated with decreases in FVIIc levels (r=0.54, p=0.0023) and FVIIag levels (r=0.59, p=0.0006) at 12 weeks of treatment with atorvastatin. No significant changes were seen in activated factor VII (FVIIa) levels. Plasma concentrations of fibrinogen were slightly, but not significantly, increased at 12 weeks. No significant changes were seen in plasminogen activator inhibitor-1 levels. The effects of atorvastatin on FVII may contribute to a decreased thrombotic potential, resulting in fewer thromboembolic events, including a reduction in coronary heart disease.
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  • Naoko Shono, Hidenori Urata, Bengt Saltin, Masao Mizuno, Taeko Harada, ...
    Type: Others
    Subject area: Others
    2002 Volume 9 Issue 1 Pages 78-85
    Published: 2002
    Released: October 31, 2003
    JOURNALS FREE ACCESS
    The effects of low intensity endurance training on skeletal muscle capillary density and serum lipoprotein levels were studied in 11 non-obese men (18-25 years). The subjects performed a 6-week training regimen (60 min, 5 times per week) at the lactate threshold (LT). Capillary density was determined in biopsy specimens obtained from the vastus lateralis muscle before and after the training. The number of capillaries per fiber (cap/fiber ratio) before training was 1.97±0.47, and increased to 2.49±0.69 after training (p<0.05). The maximal oxygen uptake (VO2 max) and LT-VO2 increased significantly by 5% (p<0.01) and 27% (p<0.01), respectively, whereas no change was observed in body weight. Low density lipoprotein cholesterol (LDL-C) tended to decrease (p=0.06). The change in the cap/fiber ratio correlated inversely with the change in the ratio of LDL-C to high density lipoprotein cholesterol (HDL-C) (r=−0.61, p<0.05). It was also positively associated with the change in HDL2-C (r=0.82, p<0.01) and inversely associated with the change in HDL3-C (r=−0.63, p<0.05). The change in LT-VO2 was inversely associated with the change in LDL-C (r=−0.62, r<0.05). These results indicate that low intensity training increases capillary density in skeletal muscle, which may explain in part the changes in the lipoprotein profiles.
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