Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
14 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
Reviews
  • Harry R Davis, Enrico P Veltri
    2007 年 14 巻 3 号 p. 99-108
    発行日: 2007年
    公開日: 2007/06/23
    ジャーナル フリー
    Zetia (ezetimibe) is a selective cholesterol absorption inhibitor, which potently inhibits the absorption of biliary and dietary cholesterol from the small intestine without affecting the absorption of fat-soluble vitamins, triglycerides or bile acids. Ezetimibe reduces the small intestinal enterocyte uptake and absorption of cholesterol by binding to Niemann-Pick C1 Like 1 (NPC1L1), which keeps cholesterol in the intestinal lumen for excretion. Ezetimibe undergoes glucuronidation to a single metabolite and localizes at the intestinal wall, where it binds with higher affinity for NPC1L1 than ezetimibe to prevent cholesterol absorption. Enterohepatic recirculation of ezetimibe and/or its glucuronide ensures repeated delivery to the intestinal site of action and limited peripheral exposure. Ezetimibe has no effect on the activity of major drug metabolizing enzymes (CYP450), which reduces any potential drug-drug interactions with other medications. Ezetimibe (10 mg/day) was found to inhibit cholesterol absorption by an average of 54% in hypercholesterolemic individuals and by 58% in vegetarians. Ezetimibe alone reduced plasma total and LDL-Cholesterol (18%) levels in patients with primary hypercholesterolemia. When ezetimibe was added to on-going statin treatment, an additional 25% reduction in LDL-C was found in patients with primary hypercholesterolemia and an additional 21% reduction in LDL-C in homozygous familial hypercholesterolemia. Ezetimibe in combination with statins produces additional reductions in plasma cholesterol levels and allows for more patients to achieve their LDL-C goals.
  • Takayuki Sakamoto, Toshiyuki Ishibashi, Yukio Maruyama
    2007 年 14 巻 3 号 p. 109-115
    発行日: 2007年
    公開日: 2007/06/23
    ジャーナル フリー
    Tissue factor (TF) is the primary initiator of the coagulation cascade. ²+ signaling is involved in TF gene expression. Monocyte chemoattractant protein-1 (MCP-1) and its receptor (CCR2) play a pivotal role in the inflammation of atherosclerosis. Although nitric oxide (NO) impairment appears to promote thrombogenicity in monocyte adhesion to endothelial cells (ECs), little is known about its mechanism. Nω-nitro-L-arginine methyl ester (L-NAME) promoted MCP-1 expression in EC culture. In response to monocyte adhesion, increased TF expression accompanied by NF-κB p65 activation was observed in L-NAME-treated ECs compared with non-treated ECs. This increased TF expression was prevented by BAPTA-AM, an intracellular ²+ chelator. Monocyte attachment to L-NAME- treated ECs increased ²+ influx compared with non-treated ECs, which was prevented by the blockade of MCP1/CCR2. These findings suggest that increased production of MCP-1 caused by L-NAME contributes to the enhancement of ²+ influx only when monocytes adhered to ECs and that this may accelerate TF expression in ECs triggered by monocyte adhesion. We demonstrate the role of ²+ influx via MCP-1/CCR2 under NO impairment in TF expression in monocyte-EC interaction.
Original Articles
  • Rody G Sy, Eva Maria C Cutiongco, Felix Eduardo R Punzalan1, Ronald S ...
    2007 年 14 巻 3 号 p. 116-121
    発行日: 2007年
    公開日: 2007/06/23
    ジャーナル フリー
    Aim: Background: HDL-C has emerged as an important independent predictor of cardiovascular disease. The FNRI-HDL and NNHes Study Group in the Philippines reported that there was a high prevalence of low HDL among Filipinos. Most cases of low HDL-C are associated with secondary causes like Metabolic Syndrome. A primary cause of reduced HDL-C such as increase Cholesteryl Ester Transfer Protein activity has been identified. Objectives: 1. To determine the phenotype and frequency of Cholesteryl Ester Transfer Protein (TaqIB) polymorphism among Filipinos with cardiovascular risk factors. 2. To determine the association of TaqIB polymorphism with HDL-C levels among Filipinos with cardiovascular risk factors. Design: Cross-sectional Study. Setting: University of the Philippines-Philippine General Hospital. Statistical Analysis: Descriptive statistics, Chi square test and Fisher's correlation test using Stata version 6.
    Methods: Fifty patients were included in this pilot study and were examined with respect to genotype, lipid profiles, blood sugar and other cardiovascular risk factors. Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphism (RFLP) and Agarose Gel Electrophoresis techniques were used to determine the CETP TaqIB Polymorphism.
    Results: Out of 50 patients, 66% were females and 34% were males with a mean age of 55 y/o and a BMI of 27 kg/m². The following risk factors were identified: hypertension (92%), dyslipidemia (88%), obesity (68%), smoking (50%), diabetes mellitus type 2 (18%) and family history of premature CAD (14%). The genotype frequencies of B1B1; B1B2; B2B2 were 40%; 50% 10% respectively. The B1B1 homozygote was associated with lower HDL-C levels (45.35 ± 8.82 mg/dL) compared to B1B2 (48.96 ± 10.10 mg/dL) and B2B2 (48.99 ± 10.13 mg/dL)).
    Conclusions: Cholesteryl Ester Transfer Protein (TaqIB) Polymorphisms exist among Filipinos with cardiovascular risk factors. The frequency of TaqIB polymorphism among Filipinos with cardiovascular risk factors were B1B1 (40%), B1B2 (50%) and B2B2 (10%). B1B1 polymorphism is more common than B2B2 and associated with low HDL-C.
  • AK Al-Mahmood, AA Ismail, FA Rashid, YN Azwany, Rabinderjeet Singh, Ge ...
    2007 年 14 巻 3 号 p. 122-127
    発行日: 2007年
    公開日: 2007/06/23
    ジャーナル フリー
    Aim: To determine the effects of lipid lowering by TLC on insulin sensitivity and secretory status of non-obese normoglycemic hyperlipidemic subjects.
    Methods: An intervention study was undertaken on 16 non-obese normoglycemic hyperlipidemic subjects. They underwent 6 months of a TLC regimen. Their insulin sensitivity and lipid status were assessed at baseline and after six months. A control group containing 16 age, sex and body mass index (BMI) matched normolipidemic subjects was also enrolled to compare the change in lipid levels and insulin sensitivity in the hyperlipidemic subjects.
    Results: The intervention showed significant reductions in insulin resistance (HOMA-IR reduced from 3.8 to 1.4, p<0.001) and improvement of insulin sensitivity (HOMA%S increased from 50.1% to 121.2%, p=0.004) in hyperlipidemic subjects with associated reductions in lipid levels.
    Conclusion: Lipid lowering in non-obese hyperlipidemic subjects may be associated with improvement of insulin sensitivity.
  • Anna Tokuno, Tsutomu Hirano, Toshiyuki Hayashi, Yusaku Mori, Takeshi Y ...
    2007 年 14 巻 3 号 p. 128-132
    発行日: 2007年
    公開日: 2007/06/23
    ジャーナル フリー
    Aim: Small dense (sd)-low-density lipoprotein (LDL) is a potent atherogenic lipoprotein. The overall atherogenicity of this lipoprotein can be precisely assessed by quantifying sd-LDL rather than by measuring the LDL size. We studied the effects of representative lipid-lowering agents (statin and fibrate) on sd-LDL-cholesterol (C) in patients with type 2 diabetes.
    Methods: Sd-LDL-C was measured by the precipitation method established by Hirano and Ito. Large buoyant (lb)-LDL-C was calculated by subtracting sd-LDL-C from LDL-C. Type 2 diabetes patients (n=72) were administered lipid-lowering agents for three months: patients with hypercholesterolemia received 1 mg of pitavastatin and those with hypertriglyceridemia received 100 mg of micronized fenofibrate.
    Results: Pitavastatin reduced LDL-C by 25% and reduced TG by 8%. The statin decreased sd-LDL-C by 26%, and lb-LDL-C by 22%. Fenofibrate reduced TG by 38% and increased HDL-C by 14%. The fibrate decreased sd-LDL-C by 23% without changing LDL-C. The pitavastatin-induced reduction of sd-LDL-C was significantly correlated with the reduction of LDL-C and apo B, whereas the fenofibrate-induced reduction of sd-LDL-C was correlated with the reduction of TG.
    Conclusion: Both statin and fibrate reduce the potency of atherogenic sd-LDL particles, but via different mechanisms: the former decreases total-LDL including sd-LDL, while the latter decreases sd-LDL specifically.
  • Kazuhiro Nakaya, Makoto Ayaori, Tetsuya Hisada, Shojiro Sawada, Nobuki ...
    2007 年 14 巻 3 号 p. 133-141
    発行日: 2007年
    公開日: 2007/06/23
    ジャーナル フリー
    Aim: The ATP binding cassette transporters A1 and G1 (ABCA1/G1) and scavenger receptor class B type I (SR-BI) are key molecules in cholesterol efflux and atherogenesis. These genes are regulated by peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptor (LXR). Telmisartan is an angiotensin type 1 receptor blocker which has been reported to act as a ligand for PPARγ. We investigated whether PPARγ-activating ARBs affect the expression of these genes and cholesterol efflux from macrophages.
    Methods and Results: Telmisartan increased ABCA1, ABCG1 and SR-BI mRNA levels in THP-1 macrophages in a dose- and time-dependent fashion. It also increased their protein levels and enhanced apoA-I- and HDL-mediated cholesterol efflux from macrophages. The knockdown of PPARγ by siRNA abolished the telmisartan-induced expression of these genes. The knockdown of LXRα resulted in the complete and partial abolishment of telmisartan-induced ABCA1 and ABCG1 expression, respectively. We also demonstrated that telmisartan-induced SR-BI expression was dependent on the PPARγ pathway but not on the LXRα pathway. A luciferase assay using an ABCA1 promoter construct showed that telmisartan activated ABCA1 transcription, which was abolished if the LXR binding element was mutated, indicating that increased ABCA1 transcription by telmisartan is LXR-dependent.
    Conclusion: Our results showed that telmisartan enhanced both apoA-I- and HDL-mediated cholesterol efflux from macrophages by increasing ABCA1, ABCG1 and SR-BI expression via PPARγ-dependent and LXR-dependent/independent pathways.
  • Yuka Nabeno, Yoshiko Fukuchi, Yasuko Matsutani, Michitaka Naito
    2007 年 14 巻 3 号 p. 142-150
    発行日: 2007年
    公開日: 2007/06/23
    ジャーナル フリー
    Aim: To analyze the influence of menopause and age on postprandial lipoprotein responses in healthy adult women.
    Method: Twenty-seven healthy young and middle-aged pre- and postmenopausal female volunteers aged 21-53 y were enrolled. They ingested OFTT cream(Jomo, Takasaki, Japan). Fasting and postprandial blood samples were obtained for up to 6 h, and serum concentrations of lipoproteins were analyzed.
    Results: In the postprandial phase, serum triglycerides(TG), remnant-like particle(RLP)-TG(RLP-TG), RLP-cholesterol(RLP-C), and TG-rich lipoprotein-TG(TRL-TG)concentrations in all groups peaked after 2 h. After 4 h, the TG, RLP-C, RLP-TG and TRL-TG concentrations in the young women returned to the fasting concentrations. However, at 6 h, these parameters in the pre- and postmenopausal women had barely returned to the fasting concentrations.
    Conclusion: The present results suggest that:(1)the magnitude of postprandial TG concentrations is dependent on age, but not on menopause;(2)clearance of remnant lipoproteins is delayed with age in pre- and postmenopausal women compared to young women, and(3)menopause is associated with an increase of RLP-C, but may not influence LDL particle size.
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