Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
5 巻 , 1 号
選択された号の論文の7件中1~7を表示しています
  • Takashi Terano, Tatsuya Shiina, Yoshihiko Noguchi, Tomoaki Tanaka, Ich ...
    1998 年 5 巻 1 号 p. 1-6
    発行日: 1998年
    公開日: 2011/09/20
    ジャーナル フリー
    Pravastatin, a HMG-CoA reductase inhibitor was found to inhibit DNA synthesis of vascular smooth muscle cells (VSMC) in a dose-dependent manner. Flow cytometric analysis demonstrated that pravastatin induced G1 arrest. Mevalonate restored the inhibitory effect of pravastatin on DNA synthesis and on cell cycle progression, suggesting the importance of mevalonate itself and/or its metabolites in VSMC proliferation. The major intermediate metabolites of mevalonate, geranylgeranyl-pyrophosphate (GGPP), farnesyl-pyrophosphate (FPP) and IPP (isopentenyl pyrophosphate) were prepared in the form of liposomes, and the effects of GGPP, FPP and IPP on pravastatin induced inhibition of VSMC proliferation and G1 arrest were examined. Only GGPP restored the pravastatin-induced inhibition of DNA synthesis and G1 arrest. Pravastatin inhibited translocation of Rho small GTPase from cytosol to membrane. By the addition of GGPP, Rho small GTPase are geranylgeranylated and translocated to membranes during G1/S transition. These data suggest that GGPP, rather than FPP or IPP, is an essential metabolite among mevalonic acid metabolites for VSMC proliferation and the G1/S transition.
  • Yasuhiro Okamoto, Kimio Satomura, Haruo Nakamura, Kyoko Takeuchi, Masa ...
    1998 年 5 巻 1 号 p. 7-12
    発行日: 1998年
    公開日: 2011/09/20
    ジャーナル フリー
    To investigate the relationship between cytologic alterations and cellular proliferation during atherosclerotic remodeling, we examined experimental atheromatous plaques by immuno-histochemistry. Plaques were formed on rabbit aortas by cholesterol-enriched diets and mechanical stimulation over a period of 2 months. Plaques were examined 1 month and 6 months after induction. We used antibodies RAM-11, HHF-35, and monoclonal anti-proliferating cell nuclear antigen (PCNA) antibody for detection of macrophages (Mø), smooth muscle cells (SMC), and PCNA, respectively. One month after induction, the plaques revealed a thickened intima with a fibrofatty histologic pattern or accumulation of foam cells. With either histologic pattern, foam cells were found to be Mø and proliferative activity was mainly observed in Mø. Six months after induction, calcification and organization were seen on the induced plaques, suggesting progression of remodeling. There were fewer Mø and more SMC compared with plaques examined 1 month after induction. Proliferative activity was observed mainly in SMC. We have demonstrated that the proliferative activity of cell types changes during remodeling of atheromatous plaques. Our results suggest an important relationship between the proliferative activity of SMC and remodeling.
  • Shinichi Takagi, Shinji Nakajima, Yoshihiro Fukuo, Akiro Terashi
    1998 年 5 巻 1 号 p. 13-20
    発行日: 1998年
    公開日: 2011/09/20
    ジャーナル フリー
    Hyperhomocysteinemia results from an impaired methionine metabolism. Sulfite oxidase, which is an important enzyme in methionine metabolism, contains molybdenum. In contrast, tungsten has a molybdenum-antagonistic effect. Thus, we hypothesized that dietary tungsten may decrease plasma homocysteine levels and influence methionine metabolism. Male New Zealand White rabbits (n =15) were fed a low-cholesterol basal diet and then placed on three different diets : 0.1% cholesterol (Chol), Chol plus 1% methionine (Met), and Chol plus Met plus 0.1% tungsten (W). The animals received these diets for 20 weeks. Biochemical tests of blood and urine were performed. Plasma homocysteine levels were significantly lower in the Chol + Met+ W group than in the Chol + Met group. Plasma levels of total cholesterol, triglyceride, lipid peroxide, and urinary 24-h taurine concentrations were higher in the Chol + Met + W group than in the Chol + Met group. In comparison, concentrations of 2, 3-diphosphoglycerate (2, 3-DPG), reduced glutathione (GSH) in erythrocytes, and urinary 24-h SO42-were lower in the Chol + Met+ W group than in the Chol + Met group. From these results, tungsten could be expected to exhibit an antiatherogenic effect. Conversely, it may have effects on atherogenic factors. Thus, tungsten may play a number of roles in the methionine metabolism
  • Yutaka Fujiwara, Seiichi Tagami, Yoshikazu Kawakami
    1998 年 5 巻 1 号 p. 21-28
    発行日: 1998年
    公開日: 2011/09/20
    ジャーナル フリー
    To clarify the relationship between circulating thrombomodulin (TM) and endothelial cell damage in diabetes mellitus, plasma levels of TM were quantitated by an enzyme-linked immunoabsorbant assay (ELISA) in 164 type 2 diabetes mellitus and 72 normal control subjects, and these levels were compared with those of von Willebrand factor antigen (vWf : Ag), thrombin-antithrombin III complexes (TAT), plasmin-α2-plasmin inhibitor complexes (PIC), fibrinogen, D-dimer, urinary albumin excretion rate (AER), intima-media thickness (IMT) and plaque score of the common carotid artery assessed with high-resolution B-mode ultrasonography. Plasma levels of TM, vWf : Ag, TAT, PIC, AER, IMT and plaque score were significantly increased in the diabetic patients compared to the normal control subjects. Plasma TM levels showed significant correlation with vWf : Ag (r = 0.350, p < 0.0001), TAT (r = 0.334, p<0.0001), PIC (r= 0.450, p<0.0001), AER (r= 0.334, p< 0.0001), IMT (r=0.181, P <0.01), plaque score (r = 0.385, p <0.0001). Among four groups of diabetic patients, divided based on their severity of diabetic retinopathy, there were no significant differences in age, sex, systolic-and diastolic blood pressure levels, HbA1c, or plasma lipid levels, although the plasma levels of TM, vWf : Ag, TAT, PIC, AER, IMT and the plaque score in the patients with proliferative retinopathy were significantly higher than those of the healthy controls and patients with simple retinopathy. Among the 43 normoalbuminuric patients without intima-media thickness or thickened plaque (AER < 30 mg/g Creatinine, IMT <1.0 mm, plaque score = 0), plasma levels of TM, vWf : Ag, TAT, PIC were significantly higher in those patients with retinopathy than in those without retinopathy. Multivariate analysis showed TM, TAT and PIC levels to be independent predictors of diabetic retinopathy. In conclusion, circulating TM reflects endothelial cell damage in patients with diabetic retinopathy, and hypercoagulability might play an important role in endothelial cell damage.
  • Hiroko Fukumoto, Zenya Naito, Goro Asano, Takumi Aramaki
    1998 年 5 巻 1 号 p. 29-35
    発行日: 1998年
    公開日: 2011/09/20
    ジャーナル フリー
    Immunohistochemical and morphometrical studies were performed to elucidate the specificity of atherosclerosis in the descending branch (the segments 5 and 6) of the left coronary artery associated with acute myocardial infarction (AMI) in the anterior wall of the heart and non-insulin-dependent diabetes mellitus (NIDDM). The NIDDM without AMI group showed diffuse intimal thickening with smooth muscle cells, combined with much more intense immunostaining of tenascin than the non-diabetic groups. The AMI without NIDDM group showed atheromatous thickening with decreased smooth muscle cells, a large number of macrophage and TUNEL-positive cells compared with the groups without AMI. However, the AMI with NIDDM group revealed atherosclerotic lesion with decreased smooth muscle cells, increased macrophages and TUNEL-positive cells associated with the increased localization of tenascin and TGF-/31 compared with the control. These findings suggest that the specificity of coronary atherosclerosis in diabetic patients may be the extensive athero-sclerotic changes associated with increased tenascin. In AMI with NIDDM, increased TGF-β1may induce apoptosis in the atheroma and coronary dysfunction, contributing to the development of acute myocardial infarction.
  • Koichi Kozaki, Yasuyoshi Ouchi
    1998 年 5 巻 1 号 p. 36-40
    発行日: 1998年
    公開日: 2011/09/20
    ジャーナル フリー
    Activin-A, a member of the TGF-β superfamily, has a variety of important biological functions. Concerning Møs, we demonstrated that MSR which has a key role in disposing of modified LDL is downregulated by activin-A. This leads to a decrease in binding, cell association, and degradation of Ac-LDL, resulting in the inhibition of foam cell formation. Follistatin, presumably by blocking the effect of intrinsic activin-A, upregulates MSR expression, thereby promoting Ac-LDL disposal and foam cell formation. Because both activin-A and MSR are induced during Mø differentiation, these results suggest that MSR expression is suppressed by simultaneous production of activin-A in an autocrine manner. In addition to Møs, activin-A and follistatin exert influences on SMCs and ECs. Examination of in vivo expression of activin-A and follistatin revealed that they are present in various atherosclerotic lesions, including human coronary arteries, suggesting that they are locally produced. Activin-A and follistatin are produced by Møs, SMCs, and ECs in vitro. Thus, the activin-A/follistatin system plays an important role in the development of atherosclerosis.
  • Jianglin Fan, Teruo Watanabe
    1998 年 5 巻 1 号 p. 41-45
    発行日: 1998年
    公開日: 2011/09/20
    ジャーナル フリー
    Hepatic lipase (HL) is an important enzyme that is involved in the metabolism of chylomicrons, intermediate density lipoproteins, and high density lipoproteins. HL may affect the liver uptake of remnant lipoproteins by modifying their compositions. HL also participates in the reverse cholesterol transport, thereby influencing the process of atherosclerosis. Several new functions of HL have recently been revealed. In this article, we review some of the recent progress based on studies using transgenic animals, with an emphasis on HL functions in remnant metabolism and atherosclerosis.
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