Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
12 巻 , 3 号
選択された号の論文の9件中1~9を表示しています
Original
  • Shigeru Morikawa, Takeshi Murakami, Hiroyuki Yamazaki, Akashi Izumi, Y ...
    2005 年 12 巻 3 号 p. 121-131
    発行日: 2005年
    公開日: 2005/07/13
    ジャーナル オープンアクセス
    The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most effective drugs for hypercholesteloremia. However, a significant side effect of statin treatment is rhabdomyolysis. In order to study the effect of statins in skeletal muscle cells, we used a DNA microarray analysis to investigate the changes in gene expression profiles brought about by statins in two skeletal muscle cell lines, namely, differentiated rat L6 myotubes and a human skeletal muscle cell line (hSkMC). In both cell lines, the statins (atorvastatin, cerivastatin and pitavastatin) induced the expression of four genes, which relate to cholesterol metabolism, namely, HMG-CoA synthase 1, HMG-CoA reductase, farnesyl diphosphate synthase and isopentenyl-diphosphate delta isomerase. Statin inhibited the synthesis of cholesterol at least five times more effectively in hSkMCs than in the hepatocytes. In addition, unlike in osteoblasts or coronary artery smooth muscle cells, statins upregulated the mRNA expression of cholesterol-associated enzymes in hSkMCs. These results provide basic information on skeletal muscle cells treated with statins and indicate that the cells are sensitive to the inhibition of HMG-CoA reductase, which may be related to the pathogenesis of muscle damage in statin therapy.
  • Toru Nakazawa, Ning Xui, Zeng Hesong, Mikio Kinoshita, Tsuyoshi Chiba, ...
    2005 年 12 巻 3 号 p. 132-137
    発行日: 2005年
    公開日: 2005/07/13
    ジャーナル オープンアクセス
    Oxysterols induce apoptosis in vascular endothelial cells in vitro, but it is not clear whether they do so in vivo. We intravenously injected an oxysterol, cholestan-3β, 5α, 6β-triol, into rats and quantitatively analyzed endothelial cell apoptosis in the aorta. Oxysterol significantly promoted apoptosis in a time- and dose-dependent fashion. The apoptosis had increased 4.5-fold 6 hrs after injection, and returned to the background level at 48 hrs. An extract of the Chinese herb Danshen as well as probucol abolished triol-induced endothelial cell apoptosis in vitro and in vivo. Since apoptotic cells are quickly cleared, oxysterol-induced apoptosis could significantly affect endothelial integrity over a long period of time. Radical scavengers may be useful for the prevention of endothelial damage.
  • Mika Kobayashi, Kenji Inoue, Eiji Warabi, Takashi Minami, Tatsuhiko Ko ...
    2005 年 12 巻 3 号 p. 138-142
    発行日: 2005年
    公開日: 2005/07/13
    ジャーナル オープンアクセス
    In the study of vascular biology, analyses of endothelial cells (EC) and smooth muscle cells (SMC) are very important. The mouse is a critical model for research, however, the isolation of primary EC from murine aorta is considered difficult. Previously reported procedures for the isolation of EC have required magnetic beads, or Fluorescence Activated Cell Sorting (FACS) to purify the cells. In addition, these procedures were applied to the heart, eyeball, or lung, not the aorta. Therefore we developed a simple method of isolating EC or SMC from the murine aorta without the need for any special equipment. To verify the purity of the cell culture, we performed both an immunofluorescence study and a DNA microarray analysis. The immunofluorescence study demonstrated specific expression of PECAM-1 in isolated EC cultures. In contrast, the isolated SMC didn’t exhibit PECAM-1, but rather, smooth muscle actin. The DNA microarray analysis demonstrated the expression of EC (16 genes) or SMC (5 genes) specific genes in each cell. This is due to the fact that pure EC or SMC can be isolated from the aorta, without the use of any special equipment. These results suggest that this method should be particularly useful for vascular biological research.
  • Ryuichi Kawamoto, Yuichiro Oka, Hitomi Tomita, Akihiro Kodama
    2005 年 12 巻 3 号 p. 143-148
    発行日: 2005年
    公開日: 2005/07/13
    ジャーナル オープンアクセス
    The aim of the present study was to evaluate sclerotic lesions of the common carotid artery by ultrasonography in 921 in-patients aged 65 years and older (77 ± 7 years) and investigate whether lipid levels were associated with carotid atherosclerosis. In men, an increased risk for carotid atherosclerosis was associated with increased levels of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). Compared to men with the lowest tertile of LDL-C levels (< 83.4 mg/dl), the adjusted odds ratio was 2.502 (95% confidence interval: 1.426−4.390) in those with the middle tertile (83.4−115.2 mg/dl), and 2.688 (1.509−4.790) in those with the highest tertile ( > 115.2 mg/dl). Like the LDL-C level, the non-HDL-C level showed a positive and linear relationship with carotid atherosclerosis. Compared to men with the lowest tertile of non-HDL-C levels ( < 101 mg/dl), the adjusted odds ratio was 2.881 (1.633−5.081) for those with the middle tertile (101−135 mg/dl), and 2.990 (1.651−5.415) for those with the highest tertile ( > 135 mg/dl). Similarly, in women, an increased risk for carotid atherosclerosis was also positively and linearly associated with LDL-C and non-HDL-C. The Non-HDL-C level is a potential predictor of risk for carotid atherosclerosis in the elderly.
  • Takeshi Takahashi, Norio Ishii, Kaori Itai, Rieko Goto, Kiichiro Higas ...
    2005 年 12 巻 3 号 p. 149-153
    発行日: 2005年
    公開日: 2005/07/13
    ジャーナル オープンアクセス
    We reported previously that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (RIs) suppressed in vitro oxidized-low density lipoprotein-induced macrophage growth. To elucidate whether HMG-CoA RIs have anti-atherogenic effects separate from their cholesterol-lowering effect, total plasma levels of cholesterol in patients with type 2 diabetes mellitus (type 2 DM) and hypercholesterolemia were reduced to normal by one-year treatment with HMG-CoA RIs and intimal-medial thickness (IMT) of the common carotid arteries (CCA) was measured. Patients with type 2 DM and hypercholesterolemia received either pravastatin (n = 15) or simvastatin (n = 15), while another group of type 2 DM patients with normocholesterolemia did not receive these agents. IMT of the CCA was measured using Powervision SSA-370A, probe 7.5 Mhz. The mean IMT and the rate of increase of IMT were relatively elevated in the order of the simvastatin-treatment group, pravastatin-treatment group, and control group. Our results suggested that HMG-CoA RIs might have anti-atherogenic effects in addition to their cholesterol-lowering effect.
  • Tsutomu Michibayashi
    2005 年 12 巻 3 号 p. 154-162
    発行日: 2005年
    公開日: 2005/07/13
    ジャーナル オープンアクセス
    Many thrombotic angiopathies originate as a result of an abnormal interaction between platelets and blood vessel walls. The present study focused on the platelet activating factor (PAF)-induced platelet aggregation mechanism and was undertaken to clarify the association between platelet aggregation and vasocontractility. Vasoconstriction was examined in perfused artery segments dissected from the central ear artery of male rabbits. Autologous platelet rich plasma (PRP) was infused into the perfusion system. Vasocontractility was examined in response to PRP plus PAF or collagen. The vasocontractile response to noradrenaline (NA-R) on perfusion of PRP plus PAF was initially augmented, then gradually attenuated. The platelet aggregation in response to PAF was constant and longlasting and moderately inhibited by nordihydroguaiaretic acid, a 12-lipoxygenase (LOX) inhibitor, but was unaffected by indomethacin, a cyclooxygenase inhibitor. The attenuated responses disappeared and NA-R was returned to the initial level on pretreatment with tetrodotoxin which excluded neurogenic components from the arterial preparation. In contrast, a repetitive NA-R to PRP plus collagen gradually increased. Thus, it may be concluded that PAF-induced platelet aggregation participates in activation of the 12-LOX pathway and is accompanied by the release of vasodepressor nerve-stimulating substances from platelets.
  • Atsuhito Saiki, Takeyoshi Murano, Fusako Watanabe, Tomokazu Oyama, Yoh ...
    2005 年 12 巻 3 号 p. 163-168
    発行日: 2005年
    公開日: 2005/07/13
    ジャーナル オープンアクセス
    It is known that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) enhance the expression- of the low-density lipoprotein (LDL) receptor and lower the level of LDL cholesterol in the blood. But, a triglyceride (TG)-lowering effect is also observed during their administration. To clarify the possibility that statins enhance LPL activity and its mechanism, the effects of statins on the expression of LPL in adipocytes were studied. When statins (pravastatin, simvastatin, atorvastatin and pitavastatin) were added to the culture medium of mouse 3T3-L1 preadipocytes at final concentrations of 1 μM for 3 days, LPL activity increased. Pitavastatin increased the activity the most. Western and Northern blotting showed that LPL protein and m-RNA were strongly expressed on the addition of pitavastatin. With the addition of mevalonate (10 μM, 3 days), LPL activity weakened significantly. Statins, especially pitavastatin, increased the expression of LPL in 3T3-L1 preadipocytes. The TG-lowering effect of pitavastatin might be mediated by enhancement of LPL production in adipocytes.
  • Ikuo Inoue, Yuichi Shinoda, Masaaki Ikeda, Kenji Hayashi, Kenta Kanaza ...
    2005 年 12 巻 3 号 p. 169-174
    発行日: 2005年
    公開日: 2005/07/13
    ジャーナル オープンアクセス
    Lipid absorption and metabolism are regulated by feeding and by the circadian system. It has been suggested that the expression of enzymes involved in lipid metabolism is directly controlled by the clock system. This study was designed to examine whether or not the CLOCK/BMAL1 heterodimer has transcriptional activity for genes via the peroxisome proliferator-activated receptor response element (PPRE). Male mice 8-12 weeks old were maintained under a 12:12 hour light-dark cycle for at least two weeks before the day of the experiment. The mRNA profiles of BMAL1 and of the PPAR target genes acyl-CoA oxidase (AOX), 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and cellular retinol binding protein II (CRBPII) were measured in intestine. The direct effects of CLOCK/BMAL1 on the promoter activities of those three enzymes were assessed in vitro by luciferase assay. The expression of PPAR target genes changed in a cyclical manner that followed expression of BMAL1. The promoter activities of the three enzymes were increased by CLOCK/BMAL1 expression. After deletion of the PPRE from the CRBPII construct, CLOCK/BMAL1 did not affect transactivation. CLOCK/BMAL1 transactivates PPAR target genes via the PPRE.
  • Hideaki Sato, Junichi Hayashi, Keiichiro Harashima, Hideaki Shimazu, K ...
    2005 年 12 巻 3 号 p. 175-180
    発行日: 2005年
    公開日: 2005/07/13
    ジャーナル オープンアクセス
    We investigated the relation of arterial stiffness, considered an independent predictor of cardiovascular events, to cardiovascular risk factors in a population-based study of 1023 subjects. An Arterial Stiffness Index (ASI) was developed to evaluate arterial stiffness based on an analysis of the pulse wave amplitude pattern acquired from measurements of brachial blood pressure. In control subjects (n = 266) without any major risk factors, the ASI was 46 ± 11, and increased with age (r = 0.346). The ASI was significantly higher in women ranging from 50 to 54 years of age than in age-matched men. The ASI rose in correlation with the number of risk factors. Subjects with two risk factors showed a significantly higher ASI than those without any risk factors (54 ± 26 vs. 46 ± 11). The ASI was significantly increased in diabetic subjects with hypertension in comparison to those without hypertension. Furthermore, hyperlipidemic subjects with hypertension showed significantly higher values than those without hypertension. ASI could be a useful predictor of cardiovascular events in hypertensive subjects with multiple risk factors.
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