著者

齊藤 昇 依岡 秀典 江渕 喜徳 土居 義典 小沢 利男 森木 利昭 原 弘

出版者

一般社団法人 日本動脈硬化学会

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.15, no.4, pp.997-1003, 1987-08-01 (Released:2011-09-21)

参考文献数

13

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One female inpatient, K. N., aged 57 years, suffered from liver cirrhosis, hypothyroidism, hypoadrenalism and bleeding tendency. After admission she received the administrations of diuretics such as furosemide and spironolactone to improve her anasarca, and also those of levothyroxine and prednisolone to fill up the deficient thyroid or adrenal functions.Slight to moderate elevations of transaminase activities, alkaline phosphatase activity of total bilirubin and increased gamma globulin concentrations were observed in this case, while low levels of triiodothyronine, total thyroxine, cortisol or urinary 17-hydroxycorticoid.Serum LCAT activity was extremely decreased, that was, 16nmol/ml/hr. She also had extremely low levels of serum lipids or apoproteins. For examples serum total cholesterol was 16mg/dl, triglyceride 18mg/dl, HDL-cholesterol 8mg/dl, phospholipid 27mg/dl, apoproteins A-I, C-II or C-III 0mg/dl, A-II 2.8mg/dl, B 10mg/dl and E 0.8mg/dl. VLDL-Chol, VLDL-TG, VLDL-PL and LDL-TG were smaller in the proportions of lipoprotein fractions, while HDL-TG, LDL-Chol and LDL-PL larger.One rare cirrhotic case with extremely low levels of serum lipids, apoproteins or lipoprotein fractions were shown in this article.

著者

中島 久実子

出版者

一般社団法人 日本動脈硬化学会

雑誌

動脈硬化 (ISSN:03862682)

巻号頁・発行日

vol.17, no.4, pp.553-570, 1989-08-01 (Released:2011-09-21)

参考文献数

69

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The interstitial fluid of arterial tissue constitutes a milieu interior for the intimal smooth muscle cells. Atherosclerotic foam cells arise from these cells when they are exposed to a high concentration of interstitial LDL. However, the available data on the concentrations of interstitial lipoproteins including LDL in normal arteries is unequivocal.In this study, the author has demonstrated the localization, form, and concentration of interstitial lipoproteins in terms of their apoproteins of A-I, A-II, B, C-II, C-III, and E in the normal intimas from 26 thoracic aortas and 19 pulmonary arteries of 45 autopsied cases (male 23, female 22, age 54±19).The localization of apoproteins was observed in the normal Intima of thoracic aorta and pulmonary artery by immunofluorescence: apo B localized mainly around the cell in the intima and along the internal elastic lamina, while apo A-I and A-II grouped in an islet form deep in the media. Apo C-II, C-III and E were sparsely present both in the intima and media. SDS-gradient PAG electrophoresis revealed all serum apoprotein bands with a _mobility corresponding to the serum counterparts.PAG disk electrophoresis showed that apoproteins were complexed with sudanophillic lipids in the interstitial fluid, and migrated in 3 bands of mobility corresponding to those of serum VLDL, LDL and HDL. Three dimensional form of recovered lipid-apoprotein complex was confirmed to be spheres of a diameter of about 500Å and 200Å by transmission and scanning electronmicroscopy.The concentrations of interstitial lipoproteins were measured by SRID for both thoracic and pulmonary interstitial fluids. Apo A-I was 5.2mg/ dl in thoracic aorta, while 0.4mg/dl in pulmonary artery, A-II 1.4mg/dl vs. 0.9mg/dl, B 18.2mg/dl vs. 10.3mg/dl, C-II 0.2mg/dl vs. 0.2mg/dl, C-III 1.1mg/dl vs. 0.4mg/dl and E 2.1mg/dl vs. 0.6mg/ dl, respectively. The concentrations of apoproteins gained in wet tissue weight were converted to the unit of mg/dl by using factors for water content of thoracic aorta 77±10%, and for pulmonary artery 81±19%, and the volume of extracellular space as 52±10% and 68±11%, respectively.These indicated that there exists a distinct difference in the concentrations of lipoproteins between serum and interstitial fluid of both thoracic and pulmonary intimas: interstitial LDL is 1/5 to 1/10 of serum counterpart, VLDL 1/5 to 1/7, and HDL 1/25 to 1/35, respectively. These lipoprotein levels maintained as a millieu interior by an endothelial barrier provides intimal cells with cholesterol necessary but sufficient for their cellular metabolism. The alteration in this milieu interior brings forth the accumulation of cholesterol in the cytoplasma of intimal cells, and leads to the formation of foam cells in the intima.

著者

Shinji Koba Makoto Ayaori Harumi Uto-Kondo Fumiaki Furuyama Yuya Yokota Fumiyoshi Tsunoda Makoto Shoji Katsunori Ikewaki Youichi Kobayashi

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.23, no.7, pp.865-877, 2016-07-01 (Released:2016-07-01)

参考文献数

42

被引用文献数

2 22

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Aim: Recent studies reported that low high-density lipoprotein (HDL)-mediated cholesterol efflux capacity rather than low HDL cholesterol (HDL-C) is strongly associated with the increased risk for coronary artery disease. It remains unclear whether exercised-based cardiac rehabilitation (CR) can increase HDL cholesterol efflux capacity.Method: This study is a retrospective analysis of stored serum from patients with acute coronary syndrome (ACS) who participated in outpatient CR program following successful percutaneous coronary intervention. We employed a cell-based cholesterol efflux system including the incubation of 3H-cholesterol labeled macrophages with apolipoprotein B-depleted serum at the onset or early phase of ACS and at 6-month follow-up periods in 57 male and 11 female patients with ACS. Cardiopulmonary exercise tests were performed at the beginning and end of CR program.Result: Fifty-seven patients completed the CR program. Compared with patients who dropped out from CR program (non-CR group), CR participants showed marked amelioration in serum lipid levels, increased efflux capacity, and improved exercise capacity. Spearman's rank correlation coefficient analysis revealed that the percent increases of efflux capacity were significantly associated with the percent increases in HDL-C (ρ=0.598, p<0.0001) and apolipoprotein A1 (ρ=0.508, p<0.0001), whereas no association between increases in efflux capacity and increases in cardiopulmonary fitness was observed. Increases in cholesterol efflux capacity were not seen in patients who continued smoking and those who did not achieve all risk factor targets and higher exercise tolerance.Conclusion: CR can markedly increase both HDL-C and HDL cholesterol efflux capacity. These results suggest that CR is a very useful therapy for reverse cholesterol transport and secondary prevention.

著者

Hideo Ohira Wao Tsutsui Yoshio Fujioka

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.24, no.7, pp.660-672, 2017-07-01 (Released:2017-07-01)

参考文献数

108

被引用文献数

344

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Intestinal flora (microbiota) have recently attracted attention among lipid and carbohydrate metabolism researchers. Microbiota metabolize resistant starches and dietary fibers through fermentation and decomposition, and provide short chain fatty acids (SCFAs) to the host. The major SCFAs acetates, propionate and butyrate, have different production ratios and physiological activities. Several receptors for SCFAs have been identified as the G-protein coupled receptor 41/free fatty acid receptor 3 (GPR41/FFAR3), GPR43/FFAR2, GPR109A, and olfactory receptor 78, which are present in intestinal epithelial cells, immune cells, and adipocytes, despite their expression levels differing between tissues and cell types. Many studies have indicated that SCFAs exhibit a wide range of functions from immune regulation to metabolism in a variety of tissues and organs, and therefore have both a direct and indirect influence on our bodies. This review will focus on SCFAs, especially butyrate, and their effects on various inflammatory mechanisms including atherosclerosis. In the future, SCFAs may provide new insights into understanding the pathophysiology of chronic inflammation, metabolic disorders, and atherosclerosis, and we can expect the development of novel therapeutic strategies for these diseases.

著者

Tenjin Nishikura Shinji Koba Yuya Yokota Tsutomu Hirano Fumiyoshi Tsunoda Makoto Shoji Yuji Hamazaki Hiroshi Suzuki Yasuki Itoh Takashi Katagiri Youichi Kobayashi

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.21, no.8, pp.755-767, 2014-08-26 (Released:2014-08-26)

参考文献数

52

被引用文献数

9 56

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Aim: The aim of the present study was to investigate how small dense low-density lipoprotein cholesterol (sdLDL-C) compared with LDL-C affect the long-term prognosis in patients with stable coronary artery disease (CAD). Methods: sdLDL-C measured by heparin magnesium precipitation and LDL particle size measured by non-denatured gradient-gel electrophoresis were compared in 190 consecutive CAD patients who underwent coronary arteriography between 2003 and 2004 who did or did not develop cardiovascular events during a seven-year follow-up period. Cardiovascular events were death caused by cardiovascular diseases(CVDs), onset of acute coronary syndrome, need for coronary and peripheral arterial revascularization, hospitalization for heart failure, surgical procedure for any CVDs, and/or hospitalization for stroke. Results: First-time cardiovascular events were observed in 72 patients. Those who experienced cardiovascular events were older and had higher prevalence rates of hypertension and diabetes; significantly higher Gensini coronary atherosclerotic scores; significantly higher levels of sdLDL-C, sdLDL-C/LDL-C, and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratios; and greater glycated hemoglobin(Hb)A1c and brain natriuretic peptide (BNP) levels. They also had significantly smaller LDL particle sizes, HDL-C, apolipoprotein A-1, and estimated glomerular filtration rate (GFR) compared with patients without cardiovascular events. Conversely, LDL-C, non-HDL-C, apolipoprotein B, remnantlike particle cholesterol, and high-sensitivity C-reactive protein (hs-CRP) levels were similar between the two groups. A Kaplan-Meyer event-free survival curve demonstrated that patients with sdLDL-C≥35 mg/dL (median level) had significantly poorer prognosis compared with those with lower sdLDL-C levels, while patients with LDL-C ≥100 mg/dL had a non-significantly lower survival rate. Conclusion: These results confirm that sdLDL-C is a very promising biomarker to predict future cardiovascular events in the secondary prevention of stable CAD.

著者

Yoshihide Yamanashi Tappei Takada Ryoya Kurauchi Yusuke Tanaka Toko Komine Hiroshi Suzuki

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.RV16007, (Released:2017-01-17)

参考文献数

78

被引用文献数

44

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Humans cannot synthesize fat-soluble vitamins such as vitamin E and vitamin K. For this reason, they must be obtained from the diet via intestinal absorption. As the deficiency or excess of these vitamins has been reported to cause several types of diseases and disorders in humans, the intestinal absorption of these nutrients must be properly regulated to ensure good health. However, the mechanism of their intestinal absorption remains poorly understood. Recent studies on cholesterol using genome-edited mice, genome-wide association approaches, gene mutation analyses, and the development of cholesterol absorption inhibitors have revealed that several membrane proteins play crucial roles in the intestinal absorption of cholesterol. Surprisingly, detailed analyses of these cholesterol transporters have revealed that they can also transport vitamin E and vitamin K, providing clues to uncover the molecular mechanisms underlying the intestinal absorption of these fat-soluble vitamins. In this review, we focus on the membrane proteins (Niemann-Pick C1 like 1, scavenger receptor class B type I, cluster of differentiation 36, and ATP-binding cassette transporter A1) that are (potentially) involved in the intestinal absorption of cholesterol, vitamin E, and vitamin K and discuss their physiological and pharmacological importance. We also discuss the related uncertainties that need to be explored in future studies.

著者

Xiang Yin Linli Zhou Fei Han Jie Han Yuanyuan Zhang Zewei Sun Wenting Zhao Zhen Wang Liangrong Zheng

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.24, no.1, pp.55-67, 2017-01-01 (Released:2017-01-01)

参考文献数

30

被引用文献数

9

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Aim: Atherosclerosis is a chronic inflammatory disease, which leads to thrombosis and acute coronary syndrome. Matrix metalloproteinase-9 (MMP-9) is involved in the stability of the extracellular matrix (ECM) and atherosclerosis plaque. Until now, it is established that lipopolysaccharide (LPS) and norepinephrine (NE) are associated with the pathological process of atherosclerosis. However, the combined effect of LPS and NE on MMP-9 is unclear. We investigated the combined effect of LPS and NE on MMP-9 expression in human monocytes and the mechanism involved in the process.Methods: THP-1 cells were cultured and treated with LPS and/or NE. MMP-9 and TIMP-1 gene and protein expression were detected by real time PCR and ELISA, respectively. MMP-9 activity was detected by gelatin zymography. Adrenoceptor antagonists and MAPKs inhibitors were used to clarify the mechanism. Pathway-related proteins were detected by Western blot.Results: We found that NE enhances LPS-induced MMP-9 and TIMP-1 expression as well as MMP-9 activity in THP-1 cells. This effect is reversed by the beta (β)-adrenoceptor antagonist propranolol, extracellular signal-regulated kinases (ERK) inhibitor U0126, and c-Jun N-terminal kinase (JNK) inhibitor SP600125. NE enhances LPS-induced ERK/JNK phosphorylation. NE up-regulates LPS-induced c-Fos expression, which is counteracted by propranolol, U0126, and SP600125. Furthermore, c-Fos silence reverses the effect of NE on MMP-9 activity.Conclusions: Our results suggest that NE enhances LPS-induced MMP-9 expression through β-adrenergic receptor and downstream ERK/JNK-c-Fos pathway. This study may help us to understand the combined effect and mechanism of NE/LPS on MMP-9 expression.

著者

Satoshi Akiba Hidenori Yamaguchi Satomi Kumazawa Mayuko Oka Takashi Sato

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.14, no.5, pp.219-225, 2007 (Released:2007-11-06)

参考文献数

40

被引用文献数

5 8

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Aim: An extract of Ginkgo Biloba L. was shown to have preventive effects on cardiovascular disorders, but the molecular mechanisms of its actions remain to be elucidated. Since matrix metalloproteinases (MMPs) are implicated in the rupture of atherosclerotic plaques and the subsequent occurrence of acute coronary syndrome, we examined the effects of a leaf extract (Ginkgolon-24) on the production of MMP-1 in human coronary smooth muscle cells stimulated with oxidized low-density lipoprotein (oxLDL) and 4-hydroxynonenal, which are factors proposed to play a pivotal role in atherogenesis.Methods: The production of MMP-1 and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 were estimated by immunoblotting. The tyrosine-phosphorylated form of platelet-derived growth factor receptor β (PDGFR-β) was analyzed by immunoprecipitation of the receptor followed by immunoblotting.Results: oxLDL and 4-hydroxynonenal accelerated the production of MMP-1 with the preceding phosphorylation of ERK1/2 and PDGFR-beta;. Pretreatment with Ginkgolon-24 inhibited the production of MMP-1 and phosphorylation of ERK1/2 induced by oxLDL and 4-hydroxynonenal, but did not affect the production and phosphorylation induced by phorbol ester. Furthermore, Ginkgolon-24 prevented tyrosine phosphorylation of the receptor induced by oxLDL and 4-hydroxynonenal.Conclusion: These results suggest that Ginkgo Biloba extract suppresses the oxLDL- and 4-hydroxynonenal-induced production of MMP-1, probably through the inhibition of PDGFR-β activation in human coronary smooth muscle cells.

著者

Masahiko Kobayashi Miyuki Kajiwara Setsuo Hasegawa

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.22, no.11, pp.1186-1196, 2015-11-02 (Released:2015-11-02)

参考文献数

19

被引用文献数

13

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Aim: We investigated the safety of 600/150 mg regimen of clopidogrel and the pharmacodynamics and pharmacokinetics of both 300/75 mg regimen and 600/150 mg regimen of clopidogrel in 72 Japanese subjects.Methods: A randomized study was conducted in healthy Japanese male subjects. Eligible subjects were stratified by dose regimen (300 mg loading dose of clopidogrel on day 1 followed by a 75 mg maintenance dose from days 2 to 7 or a 600 mg loading dose of clopidogrel on day 1 followed by a 150 mg maintenance dose from days 2 to 7) and CYP2C19 metabolizer group [extensive metabolizers (EMs), intermediate metabolizers (IMs), and poor metabolizers (PMs)]. Platelet aggregation and platelet reactivity were evaluated by measuring the maximum platelet aggregation intensity (MAI) induced by 5 and 20 μM ADP, phosphorylation of vasodilator-stimulated phosphoprotein (VASP), and P2Y12 reaction units (PRU) using the VerifyNow system, respectively. We also measured the plasma concentrations of clopidogrel and its active metabolite H4.Results: No treatment emergent adverse events in the 300/75 mg and 600/150 mg regimen were observed in EMs, IMs, and PMs. All CYP metabolizer groups exhibited a lower MAI (%) induced by ADP in the 300/75 mg and 600/150 mg clopidogrel regimens, and MAI (%) in IM group was equipotent to EM irrespective of the clopidogrel dosage. The double dose regimen decreased MAI in the PM group as equipotent to the IM group receiving the standard dose regimen without the extension of bleeding time. No clear relationship of exposure to clopidogrel and CYP2C19 function was observed, whereas active metabolite H4 exposure was likely to be related to CYP2C19 function.Conclusion: Clopidogrel in the 600/150 mg regimen was well tolerated. All CYP metabolizer groups exhibited a lower MAI (%) induced by ADP and anti-platelet activities analyzed by VASP and VerifyNow test in the 300/75 mg and 600/150 mg regimens in healthy Japanese subjects.

著者

Mariko Harada-Shiba Osamu Arisaka Akira Ohtake Tomoo Okada Hideki Suganami NK-104-PH 01 study registration group

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.23, no.1, pp.48-55, 2016-01-06 (Released:2016-01-06)

参考文献数

14

被引用文献数

2 15 2

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Aim: The purpose of this study was to evaluate the efficacy and safety of LIVALO® tablets (pitavastatin) in Japanese male children with heterozygous familial hypercholesterolemia (FH).Methods: A multicenter, randomized, double-blind, parallel study was conducted in 14 male children 10-15 years of age with heterozygous FH. Pitavastatin (1 mg/day or 2 mg/day) was administered orally for 52 weeks.The primary endpoint was the percent change in the LDL-cholesterol (LDL-C) concentrations from baseline to endpoint (repeated measures ANCOVA at Weeks 8 and 12). Secondary endpoints included the percentage of patients who achieved the target LDL-C concentration and percent changes in the levels of lipoprotein and lipid parameters at the visit performed at 52 weeks.Results: The percent change in LDL-C from baseline (mean 258 mg/dL for all patients) to the endpoint was -27.3% (95%CI; -34.0, -20.5) and -34.3% (95%CI; -41.0, -27.5) in the patients receiving 1 mg and 2 mg of pitavastatin, respectively. Stable reductions in the total cholesterol (TC), non-HDL cholesterol (non-HDL-C), apolipoprotein B (Apo-B) and LDL-C levels and non-HDL-C/HDL-C and Apo-B/Apo-A1 ratios were observed up to 52 weeks in both groups. One patient in each dose group (14%) reached the treatment target level of 130 mg/dL.Adverse events were observed in seven (100%) patients receiving 1 mg and five (71%) patients receiving 2 mg of pitavastatin, although none were considered related to the study treatment. One patient in the 1 mg group reported a musculoskeletal AE; however, it was attributed to recent excessive exercise.Conclusions: Pitavastatin significantly reduced the LDL-C levels and was well tolerated when administered at usual adult doses in 14 male children 10-15 years of age with heterozygous FH. Pitavastatin is a promising therapeutic agent for pediatric dyslipidemia with few safety concerns.

著者

Sulette de Villiers Albe Swanepoel Janette Bester Etheresia Pretorius

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.32748, (Released:2015-12-19)

参考文献数

57

被引用文献数

1 31

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Central to the pathogenesis of ischaemic stroke are the normally protective processes of platelet adhesion and activation. Experimental evidence has shown that the ligand-receptor interactions in ischaemic stroke represent a thrombo-inflammatory cascade, which presents research opportunities into new treatment. However, as anti-platelet drugs have the potential to cause severe side effects in ischaemic stroke patients (as well as other vascular disease patients), it is important to carefully monitor the risk of bleeding and risk of thrombus in patients receiving treatment. Because thrombo-embolic ischaemic stroke is a major health issue, we suggest that the answer to adequate treatment is based on an individualized patient-centered approach, inline with the latest NIH precision medicine approach. A combination of viscoelastic methodologies may be used in a personalized patient-centered regime, including thromboelastography (TEG®) and the lesser used scanning electron microscopy approach (SEM). Thromboelastography provides a dynamic measure of clot formation, strength, and lysis, whereas SEM is a visual structural tool to study patient fibrin structure in great detail. Therefore, we consider the evidence for TEG® and SEM as unique means to confirm stroke diagnosis, screen at-risk patients, and monitor treatment efficacy. Here we argue that the current approach to stroke treatment needs to be restructured and new innovative thought patterns need to be applied, as even approved therapies require close patient monitoring to determine efficacy, match treatment regimens to each patient's individual needs, and assess the risk of dangerous adverse effects. TEG® and SEM have the potential to be a useful tool and could potentially alter the clinical approach to managing ischaemic stroke. As envisaged in the NIH precision medicine approach, this will involve a number of role players and innovative new research ideas, with benefits that will ultimately only be realized in a few years. Therefore, with this ultimate goal in mind, we suggest that an individualized patient-orientated approach is now available and therefore already within our ability to use.

著者

Ryo Naito Katsumi Miyauchi Hirokazu Konishi Shuta Tsuboi Manabu Ogita Tomotaka Dohi Takatoshi Kasai Hiroshi Tamura Shinya Okazaki Kikuo Isoda Hiroyuki Daida

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.32284, (Released:2015-11-11)

参考文献数

16

被引用文献数

1 5

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Aim: Current Japanese guidelines state the target level of low-density lipoprotein cholesterol (LDL-C) of <100mg/dL for secondary prevention of coronary artery disease (CAD). However, this level was set considering the results of trials mainly conducted in Western countries. In addition, the effect of achieving target LDL-C on secondary prevention is unknown. Methods: We examined the effects of achieving target LDL-C on clinical outcomes. Patients who underwent percutaneous coronary intervention at Juntendo University Hospital (Tokyo, Japan) from 2004 to 2010 and received follow-up coronary angiography (CAG) were analyzed. The study population was divided into two groups based on the follow-up LDL-C. The incidence of major adverse cardiovascular events within 3 years after the follow-up CAG was examined. Results: A total of 1321 consecutive patients were enrolled. Sixty-three percent of the patients achieved the target LDL-C. The rate of 3-year events was lower in the group that achieved the target LDL-C (achieved group). The adjusted relative risk reduction in the achieved group was 26% (p=0.02). In the sub-analysis among the four groups stratified by baseline LDL-C of 140 and follow-up LDL-C of 100, the adjusted hazard ratio for 3-year events was 1.84 (95% confidence interval; 1.10-3.24)in Group 3 (baseline <140, follow-up ≥100) and 2.05 (1.18-3.74) Group 4 (baseline ≥140, follow-up ≥100) [Group 2 (baseline ≥140, follow-up <100) as reference]. Conclusions: Our data suggested that follow-up LDL-C <100mg/dL was appropriate for secondary prevention of CAD in Japanese population.

著者

Sumiko Yoshida Yasumasa Ikeda Ken-ichi Aihara

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.31047, (Released:2015-10-30)

参考文献数

105

被引用文献数

1 19

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Although many clinical studies have shown that a low testosterone level is associated with cardiovascular diseases, the role of androgens in cardiovascular physiology and pathophysiology remains controversial. Androgens exert various actions in their target organs, and the androgen receptor (AR) is widely distributed in several tissues, including endothelial cells, smooth muscle cells, and fibroblasts, in the vascular system. Biological activities of androgens are predominantly mediated through the AR by the transcriptional control of target genes and interaction with multiple signaling pathways. To clarify the molecular mechanisms of androgens in cardiovascular disease, we examined a pathological model using AR knockout mice and showed that the androgen–AR system has protective effects on cardiovascular remodeling against cardiovascular stress. In this review, we focus on the role of the androgen–AR system in angiogenesis after ischemic stress.

著者

Junji Kobayashi Kazuya Miyashita Katsuyuki Nakajima Hiroshi Mabuchi

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.31617, (Released:2015-07-21)

参考文献数

87

被引用文献数

3 66

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Hepatic lipase (HL) is a key enzyme catalyzing the hydrolysis of triglycerides (TG) and phospholipids (PLs) in several lipoproteins. It is generally recognized that HL is involved in the remodeling of remnant, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and the production of small, dense low-density lipoproteins (sd-LDLs).On the other hand, it is unclear whether HL accelerates or retards atherosclerosis. From the clinical point of view, HL deficiency may provide useful information on answering this question, but the rarity of this disease makes it impossible to conduct epidemiological study.In this review, we describe a comprehensive and updated view of the clinical significance of HL on lipid and lipoprotein metabolism.

著者

Takao Sato Tomoki Kameyama Takashi Ohori Akira Matsuki Hiroshi Inoue

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.21, no.10, pp.1031-1043, 2014-10-24 (Released:2014-10-24)

参考文献数

53

被引用文献数

1 15

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Aim: Epicardial adipose tissue (EAT) is a pathogenic fat depot that may be associated with coronary atherosclerosis and cardiovascular events. Because eicosapentaenoic acid (EPA) has been reported to exert cardiovascular protective effects, we aimed to assess the effects of EPA on the volume of visceral adipose tissue, including EAT and abdominal visceral adipose tissue (AVAT), using multislice computed tomography (CT). Methods: In 30 patients with coronary artery diseases (9 women; mean age, 67.2±5.4 years), EAT and AVAT volumes were compared between the control group (n=15, conventional therapy) and the EPA group (n=15, conventional therapy plus purified EPA 1800 mg/day) during a six-month period. EAT was defined as any pixel that had CT attenuation of -150 to -30 Hounsfield units (HU) within the pericardial sac. Results: After the six-month follow-up, the serum EPA level increased from 59.9±18.8 to 177.2± 3.3 μg/mL in the EPA group (p<0.01), but no increase was noted in the control group. Similarly, the EPA/arachidonic acid (AA) ratio increased from 0.39±0.12 to 1.22±0.28 in the EPA group (p<0.01), with no significant increase in the control group. The AVAT and EAT volumes decreased in the EPA group but were unchanged in the control group (AVAT, −11.6±17.0 vs. +8.8±13.6 cm2, p<0.01; EAT, −7.3±8.3 vs. +8.7±8.8 cm3, p<0.01). Moreover, the change in the AVAT volume negatively correlated with the change in EPA (r=−0.58, p<0.01) and EPA/AA levels (r=−0.53, p<0.01). A similar negative correlation in these parameters was also observed for the EAT volume. Conclusions: Oral intake of purified EPA appears to be associated with reductions in EAT and AVAT volumes.

著者

Shigetsugu Tsuji Atsushi Nohara Yoshiaki Hayashi Isao Yoshida Rie Oka Tadashi Moriuchi Tomomi Hagishita Susumu Miyamoto Ayako Suzuki Toshihide Okada Masakazu Yamagishi

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.25825, (Released:2014-10-23)

参考文献数

42

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Aim: The role of gastrectomy in glycemic control has been established in the current era of bariatric surgery for obesity. Gastrectomy in obese patients is associated with increased levels of high-density lipoprotein cholesterol (HDL-C). However, limited data on the effects of gastrectomy in nonobese patients are available. We herein investigated the long-term plasma lipid changes in nonobese patients who had undergone gastrectomy. Methods: Patients were enrolled as part of routine healthcare examinations from 1984 to 2003. Preoperative and postoperative data from patients who had undergone curative gastrectomy were analyzed for up to 10 years postoperatively. Three age- and sex-matched controls were assigned to each case. Results: Sixty-four nonobese patients without diabetes mellitus or a history of having taken lipidlowering drugs who underwent curative gastrectomy during the study period were enrolled (60 subtotal gastrectomies, four total gastrectomies). The median follow-up period was 7.6 years. The mean body mass index was 9.6% lower one year after gastrectomy (p<0.01), then plateaued with a slight recovery. Intriguingly, the preoperative HDL-C level was 21% higher one year after gastrectomy (p<0.01), increased by another 30% six years after gastrectomy and remained at this level for the rest of the follow-up period. No significant changes in the HDL-C level were observed in the controls. The degree of HDL-C elevation was consistently significant, irrespective of the baseline triglyceride level, HDL-C level or body weight. Conclusions: Gastrectomy in nonobese patients was associated with consistent and distinct long-term HDL-C elevations and body mass index reductions.

著者

Koichi Kaikita Takamichi Ono Satomi Iwashita Naoki Nakayama Koji Sato Eiji Horio Shinichi Nakamura Kenichi Tsujita Shinji Tayama Seiji Hokimoto Tomohiro Sakamoto Koichi Nakao Shuichi Oshima Seigo Sugiyama Hisao Ogawa

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.21, no.1, pp.64-76, 2014-01-23 (Released:2014-01-23)

参考文献数

41

被引用文献数

4 13 1

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Aim: Carriers of the reduced-function CYP2C19 allele receiving dual antiplatelet therapy (DAPT) with aspirin and clopidogrel exhibit diminished platelet inhibition and an increased risk of events. The purpose of this study was to investigate the effects of CYP2C19 gene variants on platelet function tests and coagulation and inflammatory biomarkers in patients undergoing elective percutaneous coronary intervention (PCI). Methods: This prospective, observational, multicenter study enrolled 104 consecutive Japanese patients undergoing elective PCI. We examined the CYP2C19 genotype, platelet function tests, the levels of coagulation and inflammatory biomarkers and the serum levels of high-sensitivity troponin T (hs-TnT) before, immediately after and one, two and 28 days after PCI. Results: A total of 68 (65%) of the 104 enrolled patients were carriers of the CYP2C19 reducedfunction allele. On-clopidogrel platelet aggregation (PA), measured using light transmittance aggregometry and the VerifyNow® P2Y12 system, and the platelet reactivity index (PRI) were significantly higher at all time points in the carriers than in the noncarriers (p<0.05), whereas there were no differences in the levels of the coagulation and inflammatory biomarkers or serum hs-TnT. Simple and multiple logistic regression analyses identified on-clopidogrel PA and PRI as being significant predictors of carriers of the CYP2C19 reduced-function allele. Conclusions: The present study suggests that platelet function tests, but not coagulation, inflammatory or cardiac biomarkers, are useful for identifying carriers of CYP2C19 reduced-function gene variants and monitoring the efficacy of DAPT in patients undergoing elective PCI.

著者

Ryo Ito Noriko Satoh-Asahara Hajime Yamakage Yousuke Sasaki Shinji Odori Shigeo Kono Hiromichi Wada Takayoshi Suganami Yoshihiro Ogawa Koji Hasegawa Akira Shimatsu

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.19976, (Released:2013-11-22)

参考文献数

56

被引用文献数

4 36

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Aim: Previous epidemiological studies demonstrated that the ratio of n-6 to n-3 polyunsaturated fatty acids is associated with cardiovascular diseases. We herein investigated whether the beneficial effect of highly purified eicosapentaenoic acid(EPA) on arterial stiffness is associated with changes in the ratio of polyunsaturated fatty acids, such as EPA, docosahexaenoic acid(DHA) and dihomo-γ-linolenic acid(DGLA), relative to arachidonic acid(AA), in obese Japanese patients with dyslipidemia. Methods: The EPA/AA, DHA/AA and DGLA/AA ratios were compared between obese patients with(n=94) and without (n=31) dyslipidemia. Among the former group, 88 patients received either highly purified EPA treatment(1.8g daily, n=45) or treatment without EPA(control, n=43). Results: At baseline, the ratios of DHA/AA and DGLA/AA were significantly(P<0.05) higher in obese patients with dyslipidemia than in those without, while the EPA/AA ratio was similar between patients with and without dyslipidemia. EPA significantly reduced the hemoglobin A1c, total cholesterol, triglycerides, CRP, cardio-ankle vascular index(CAVI)(an index of arterial stiffness) and the DGLA/AA ratio relative to the control at three months after the treatment. On the other hand, EPA significantly increased the adiponectin level and EPA/AA ratio(P<0.05). A multivariate regression analysis revealed that only age, an increase in the EPA/AA ratio and a decrease in the CRP level were significant determinants of a reduction of the CAVI by EPA. Conclusion: These findings suggest that EPA improves the arterial stiffness in association with an increase in the EPA/AA ratio and a decrease in inflammation in obese patients with dyslipidemia.

著者

Hidenori Arai Akira Yamamoto Yuji Matsuzawa Yasushi Saito Nobuhiro Yamada Shinichi Oikawa Hiroshi Mabuchi Tamio Teramoto Jun Sasaki Noriaki Nakaya Hiroshige Itakura Yuichi Ishikawa Yasuyoshi Ouchi Hiroshi Horibe Tohru Egashira Hiroaki Hattori Nobuo Shirahashi Toru Kita

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.12, no.5, pp.240-250, 2005 (Released:2005-10-05)

参考文献数

53

被引用文献数

27 31

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We studied the association of six common polymorphisms of four genes related to lipid metabolism with serum lipid levels. We selected single-nucleotide polymorphisms (SNPs) in the genes for cholesteryl ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic lipase (LIPC), and apolipoprotein CIII (APOC3), and studied 2267 individuals randomly selected from the participants of Serum Lipid Survey 2000. There was a significant association of CETP polymorphism (D442G, Int14 +1 G → A, and TaqIB), LPL polymorphism (S447X), and LIPC polymorphism (−514 → CT) with HDL-cholesterol levels. We also found a significant association of LPL polymorphism (S447X) and APOC3 polymorphism (SstI) with triglyceride levels. This is the largest database showing the association of common genetic variants in lipid metabolism with serum lipid levels in the general Japanese population. Further study is necessary to elucidate the role of these gene polymorphisms in cardiovascular events.

著者

Miyako Yuasa-Kawase Daisaku Masuda Taiji Yamashita Ryota Kawase Hajime Nakaoka Miwako Inagaki Kazuhiro Nakatani Kazumi Tsubakio-Yamamoto Tohru Ohama Akifumi Matsuyama Makoto Nishida Masato Ishigami Toshiharu Kawamoto Issei Komuro Shizuya Yamashita

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.20, no.5, pp.514-515, 2013 (Released:2013-05-29)

参考文献数

48