Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Volume 11 , Issue 4
Showing 1-7 articles out of 7 articles from the selected issue
Reviews
  • Masashi Shiomi, Takashi Ito, Satoshi Yamada, Seinosuke Kawashima, Jian ...
    2004 Volume 11 Issue 4 Pages 184-189
    Published: 2004
    Released: September 09, 2004
    JOURNALS FREE ACCESS
    It is generally considered that coronary rupture-prone plaques play an important role in the onset of sudden cardiac events (acute coronary syndromes/sudden cardiac death). However, it is not clear which factors or stimuli are required to trigger plaque rupture and whether coronary plaques without occlusive thrombi can cause sudden cardiac events. To address these issues, recently, we developed a rabbit model of spontaneous myocardial infarction [the Watanabe heritable hyperlipidemic (WHHL) MI rabbit] and found that this model possessed several types of coronary plaques that are possibly correlated to sudden cardiac events. Although many of the coronary plaques of the WHHLMI rabbits appeared histologically to be rupture-prone in nature, true rupture was detected only in the few animals that died of MI. In addition, no occlusive thrombus was detected in any WHHLMI rabbit. These findings suggest that some additional stimuli play a definitive role in causing disruption of rupture-prone plaques and thrombosis. Nearly-occluded plaques caused by a luminal macrophage accumulation are the most common feature of WHHLMI rabbits, suggesting that they are responsible for sudden cardiac events. The WHHLMI rabbit could be a useful model for studying the mechanism(s) of plaque rupture and thrombogenesis if plaque rupture/thrombus formation is induced in the rupture-prone plaques of WHHLMI rabbits by administration of additional triggering factors, and could provide a novel means for developing new therapies.
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  • Masahiko Okada, Takayuki Matsuto, Takashi Miida, Konen Obayashi, Ying ...
    2004 Volume 11 Issue 4 Pages 190-199
    Published: 2004
    Released: September 09, 2004
    JOURNALS FREE ACCESS
    Despite a long history of studies on lipid abnormalities, numerous problems in laboratory technologies and techniques remain unresolved. One of the most commonly tested molecules is low-density lipoprotein (LDL) cholesterol, and a homogenous assay technique for measurement of this molecule has recently been introduced. Although the method represents remarkable technological breakthroughs with great potential for improving lipoprotein analysis, some discrepancies exist among assay protocols. Even for direct measurement of high-density lipoprotein (HDL) cholesterol, which has widely been accepted, there are still large discrepancies among data obtained by different protocols. Oxidatively modified LDL is an independent factor that is considered to directly contribute to the pathogenesis of early atherosclerosis. Lipid peroxidation products, surface charge, and spectrophotometric patterns are all applicable to the evaluation of in vitro oxidation. Only enzyme-linked immunosorbent assays using monoclonal antibodies have a potential for clinical use, but such methods are not yet standardized. There is also increasing evidence for the presence of anti-oxidized LDL autoantibodies in human sera, but the diagnostic utility remains controversial. In addition, small dense LDL has recently attracted much attention as an independent risk factor. Although this is a potential target of oxidization, a robust and simple analytical method does not yet exist. This review presents the current state of laboratory technologies for testing lipid abnormalities.
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  • Sadao Takahashi, Juro Sakai, Takahiro Fujino, Hiroaki Hattori, Yasuo Z ...
    2004 Volume 11 Issue 4 Pages 200-208
    Published: 2004
    Released: September 09, 2004
    JOURNALS FREE ACCESS
    The very low-density lipoprotein (VLDL) receptor is a member of the low-density lipoprotein (LDL) receptor family. In vitro and in vivo studies have shown that VLDL receptor binds triglyceride (TG)-rich lipoproteins but not LDL, and functions as a peripheral remnant lipoprotein receptor. VLDL receptor is expressed abundantly in fatty acid-active tissues (heart, skeletal muscle and fat), the brain and macrophages. It is likely that VLDL receptor functions in concert with lipoprotein lipase (LPL), which hydrolyses TG in VLDL and chylomicron. In contrast to the LDL receptor, VLDL receptor binds apolipoprotein (apo) E2/2 VLDL particles as well as apoE3/3 VLDL, and the expression is not down-regulated by intracellular lipoproteins. Recently, various functions of the VLDL receptor have been reported in lipoprotein metabolism, metabolic syndrome/atherosclerosis, cardiac fatty acid metabolism, neuronal migration and angiogenesis/tumor growth. Gene therapy of VLDL receptor into the liver showed a benefit effect for lipoprotein metabolism in both LDL receptor knockout and apoE mutant mice. Beyond its function as a peripheral lipoprotein receptor, possibilities of its physiological function have been extended to include signal transduction, angiogenesis and tumor growth.
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Original Articles
  • Atsuhito Saiki, Yoh Miyashita, Kiyoji Wakabayasi, Noriaki Kameda, Kohj ...
    2004 Volume 11 Issue 4 Pages 209-214
    Published: 2004
    Released: September 09, 2004
    JOURNALS FREE ACCESS
    Generally, it is considered that visceral fat brings insulin resistance and hyper-insulinemia, in the mechanisms of metabolic syndromes. However, whether hyperinsulinemia brings about accumulation of visceral fat is not clear. We followed a case of insulinoma that caused primary hyperinsulinemia, and measured the change in visceral fat and insulin resistance before and after surgical resection of the insulinoma. A 58-year-old woman was admitted to investigate the cause of spontaneous hypoglycemia. An oral glucose tolerance test (OGTT) showed hyperinsulinemia with a high basal level and a glucagon infusion test showed an abnormally high insulin level. Abdominal computed tomography (CT) scan showed an accumulation of visceral fat. Selective celiac angiography showed a pancreatic tumor shadow. Under a diagnosis of insulinoma, the pancreatic body and tail were removed. At 3 months after the operation, the visceral fat area had decreased from 132.6 to 64.2 cm2. The fasting serum total cholesterol and triglyceride were also reduced. In addition, high-density lipoprotein cholesterol and preheparin serum lipoprotein lipase mass had increased. The midband on the polyacrylamide gel disc electrophoresis of lipoproteins, which appeared before operation, had disappeared completely. An OGTT showed a non-diabetic pattern after the operation. These results suggest that hyperinsulinemia might be one of the factors that enhance visceral adiposity and insulin resistance.
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  • Akihiro Yoshida, Masaaki Kouwaki, Yasuko Matsutani, Yoshiko Fukuchi, M ...
    2004 Volume 11 Issue 4 Pages 215-219
    Published: 2004
    Released: September 09, 2004
    JOURNALS FREE ACCESS
    Objective: We examined the usefulness of the serum total cholesterol (TC)/triglyceride (TG) and LDL-cholesterol (LDL-C)/TG ratios for predicting the presence of small, dense LDL, by comparing them with the established indicators of small, dense LDL, such as the LDL-migration index (LDL-MI) and LDL-C/Apolipoprotein B (ApoB) ratio.
    Materials and methods: Fasting serum lipid was analyzed in 99 Japanese hyperlipidemic and normolipidemic subjects (34 males and 65 females, 59.4 ± 11.9 years old).
    Results: A good negative correlation was observed between LDL-MI and log (TC/TG) (R2 = 0.473, p < 0.0001). There was a strong positive correlation between LDL-C/ApoB and log (TC/TG) (R2 = 0.665, p < 0.0001). Similar results were obtained using LDL-C instead of TC. Using LDL-MI > 0.4 as an indicator of small, dense LDL, the upper limit of TG was estimated to be 140−142 mg/dl.
    Conclusion: TC/TG and LDL-C/TG may offer a convenient and simple clinical tool for predicting the presence of small, dense LDL. Particularly, TC/TG could be an easy-to-use indicator of small, dense LDL for general practitioners.
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  • Osamu Arisaka, Megumi Kojima, Yuzuru Yamazaki, Sanae Kanazawa, Satomi ...
    2004 Volume 11 Issue 4 Pages 220-223
    Published: 2004
    Released: September 09, 2004
    JOURNALS FREE ACCESS
    To clarify the relationship between the expression of atherogenic small, dense low-density lipoprotein (SDLDL) and underlying lipid metabolic abnormalities, the prevalence of SDLDL in relation to the serum lipid phenotype was analyzed in 229 children. The LDL particle size was measured using gradient gel electrophoresis, and a particle size of less than 25.5 nm was considered to represent SDLDL. The overall prevalence of SDLDL in the sample population was 8.2% (19/229; 11/117 for boys and 8/112 for girls).
    Hyperlipidemia phenotype IIb (elevated concentrations of both triglyceride [TG] and total cholesterol [TC]) was strongly associated with SDLDL in 83% (5/6) of the subjects. An elevated TG concentration (phenotype IV) was associated with SDLDL in 55% (10/18) of the subjects. The association between hyperlipidemia phenotype IIa (elevated TC but a normal TG concentration) and SDLDL was quite low (2%; 1/56), but SDLDL was detected in 5% (8/155) of the subjects who presented with normolipidemia.
    Therefore, these findings suggest that the expression of SDLDL is largely related to lipid abnormalities characterized by phenotype IIb or IV, the underlying metabolic abnormality of which is suspected to be insulin resistance; however, an additional mechanism for the formation of SDLDL that functions independently of plasma lipid abnormalities also seems to exist.
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  • Yutaka Mori, Yoshiki Tokutate, Fumiki Oana, Akane Matsuzawa, Satoshi A ...
    2004 Volume 11 Issue 4 Pages 224-231
    Published: 2004
    Released: September 09, 2004
    JOURNALS FREE ACCESS
    The effect of short-term bezafibrate (BF) administration over time on the expression of UCP mRNA in the tissues was examined in Otsuka Long Evans Tokushima Fatty (OLETF) rats. Eight-week-old rats were divided into a high-dose (100 mg/kg) BF group (n = 15), a low-dose (10 mg/kg) BF group (n = 15) and a control group (n = 15), and followed for 14 days. Feed intake by the high-dose BF group increased significantly between days 10 and 14 of administration. Triglyceride, free fatty acid, and T4 levels decreased significantly in a dose-dependent manner in the high-dose BF group. Leptin and insulin levels significantly decreased on days 3 and 7. Throughout the study period, liver UCP2 mRNA increased in the high-dose BF group. On day 3 of BF administration, the levels of UCP2 mRNA expression in the skeletal muscles as well as UCP3 mRNA expression in the WAT were significantly increased in the high-dose BF group. PPAR-α mRNA significantly increased in the liver on day 3 of BF administration. We thus conclude that the PPAR-α-mediated effects of BF on the expression of liver UCP2 may be one of the factors that helped to decrease insulin levels.
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