Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
13 巻 , 3 号
選択された号の論文の6件中1~6を表示しています
Reviews
  • Jun Sasaki, Mikio Iwashita, Suminori Kono
    2006 年 13 巻 3 号 p. 123-129
    発行日: 2006年
    公開日: 2006/07/12
    ジャーナル フリー
    Large-scale clinical trials have established that statin use for lowering blood cholesterol is beneficial in reducing atherosclerotic cardiovascular diseases in different populations. However, the general reputation of statins seems to be clouded by a potential adverse effect of a class of statins on glucose metabolism. This paper reviewed clinical data of statins regarding the effects on diabetes mellitus and glucose metabolism. At least five randomized controlled studies, primarily investigating the protective effect of statins on the risk of cardiovascular diseases, have addressed the effect of statins on glucose metabolism in Western countries. One study showed that pravastatin (40 mg/day) was protective against the development of diabetes mellitus. Two studies of atorvastatin (10 mg/day) and one study of simvastatin (40 mg/day) showed no measurable effect of these regimens on the risk of diabetes mellitus or the clinical course of diabetes mellitus. One study of atorvastatin (80 mg/day) versus pravastatin (40 mg/day) suggested a deterioration of glucose metabolism associated with a high dose of atorvastatin. In Japan, a few case reports have noted a potential adverse effect of atorvastatin on glycemic control in patients with diabetes mellitus; however, seven clinical trials have showed no such effect of atorvastatin although these studies were relatively small in size and short in follow-up. Only one of the two observational studies suggested a possible adverse effect of atorvastatin on glycemic control. Evidence is extremely limited regarding atorvastatin use and deterioration in glycemic control, and further studies are needed to draw a conclusion on this issue.
  • Taro Matsumoto, Hideo Mugishima
    2006 年 13 巻 3 号 p. 130-135
    発行日: 2006年
    公開日: 2006/07/12
    ジャーナル フリー
    Vascular endothelial growth factor (VEGF)-A plays a critical role in vascular development and angiogenesis through its binding and activation of VEGF receptor-2 (VEGFR-2). The binding of VEGF-A to VEGFR-2 causes receptor dimerization, kinase activation and autophosphorylation of specific tyrosine residues within the dimeric complex. Tyrosine(Y)951 in the kinase-insert domain, Y1054 and Y1059 in the kinase domain and Y1175 and Y1214 in the C-terminal tail have been shown to serve as autophosphorylation sites. Phosphorylated Y1175 creates a binding site for phospholipase Cγ1 (PLC-γ1) and Shb. Activation of PLC-γ1 and Shb regulates VEGF-A-dependent cell proliferation and cell migration, respectively. Phosphorylated Y951 binds and mediates tyrosine phosphorylation of the T-cell-specific adaptor protein (TSAd), which is expressed in endothelial cells. Y951-mediated coupling of VEGFR-2 and TSAd is critical for VEGF-A-induced cell migration and actin reorganization, and for pathological angiogenesis. These phosphorylation sites may be useful targets for the development of anti-angiogenic therapies to treat atherosclerosis and cancer.
Original Artivles
  • Hideaki Komiya, Yutaka Mori, Takuo Yokose, Naoyuki Kurokawa, Naoko Hor ...
    2006 年 13 巻 3 号 p. 136-142
    発行日: 2006年
    公開日: 2006/07/12
    ジャーナル フリー
    We investigated the relationship between insulin reaction and glycemic control in a 75-g oral glucose tolerance test of lipid in the paraspinal muscles using computed tomography (CT). The subjects were 79 males aged from 30 to 60 years old whose body mass index (BMI) was 25 or more. Those who had already been diagnosed as having type-2 diabetes mellitus in a regular health check and whose fasting plasma glucose was 126 mg/dl or more were excluded. Abdominal CT scan at the umbilicus level was conducted, and the visceral fat area (VFA) and subcutaneous fat area (SFA) were obtained. As an index of the relative lipid content within muscle, the mean skeletal muscle attenuation (MA) was determined. The age-adjusted odds ratio caused by the MA size for each variable was calculated. Compared with those with smaller intramuscular fat volume, those with larger volume demonstrated 8.75 times higher BMI, 3.73 times higher VFA and 2.88 times higher HOMA-IR. A significant difference was observed between the groups with high and low lipid content in the muscle in the values of Age, BMI, VFA, Fasting immunoreactive insulin (IRI) and HOMA-IR. It was suggested that MA of the paraspinal muscles reflected fat content, and this regional body composition parameter was closely related to insulin secretion response and glycemic control.
  • AK Al-Mahmood, AA Ismail, FA Rashid, Wan Mohamed
    2006 年 13 巻 3 号 p. 143-148
    発行日: 2006年
    公開日: 2006/07/12
    ジャーナル フリー
    There are numerous reports on insulin resistance in subjects with hypertriglyceridemia but most of the studies involved obese or diabetic subjects. We were interested to study such events but in a population free from other confounders influencing insulin sensitivity (i.e., obesity, glucose intolerance and hypertension). From the population of a cross-sectional study we obtained 12 subjects with isolated hypertriglyceridemia and compared their insulin sensitivity with that of normolipidemic subjects in that study. Insulin sensitivity and secretory status were computed using homeostasis model assessment (HOMA) software. The insulin sensitivity of hypertriglyceridemic subjects was found to be lower than in normolipidemic subjects. For the hypertriglyceridemic subjects, insulin sensitivity (HOMA%S) was 60.07% (values adjusted for age, BMI, waist circumference, and cholesterol levels), which was substantially lower than that of normolipidemic subjects (150.03%; p<0.001). The insulin secretory status (HOMA%B) of the two groups was 248.17% and 124.63%, respectively, and significantly different (p<0.001). Relative insulin resistance, HOMA-IR, of the two groups was 4.90 and 1.54, respectively. We therefore concluded that in comparison with normolipidemic subjects, the insulin sensitivity of otherwise healthy non-obese hypertriglyceridemic subjects was lower, and that B cells had to work harder to compensate for the lowered insulin sensitivity.
  • Hidehisa Sasaki, Saburo Kanai, Tomokazu Oyama, Yoh Miyashita, Shigeo Y ...
    2006 年 13 巻 3 号 p. 149-157
    発行日: 2006年
    公開日: 2006/07/12
    ジャーナル フリー
    The effects of combination therapy of angiotensin II receptor blockers (ARBs) and a calcium antagonist, benidipine hydrochloride, on glucose and lipid metabolism and pulse pressure were studied in elderly hypertensive patients with type 2 diabetes mellitus. Twenty-five hypertensive diabetic patients aged 65 years or older, who had been receiving candesartan cilexetil, were administered benidipine hydrochloride (4 mg/day) and followed for 4 months. After 4 months, systolic and diastolic blood pressure decreased significantly from 154/91 mmHg to 139/78 mmHg (p<0.01 versus before benidipine hydrochloride administration). Body mass index (BMI) and glycosylated hemoglobin (HbA1c) were apparently reduced but the changes were not statistically significant. The serum lipid profile showed no significant changes in serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Serum lipoprotein lipase mass levels (preheparin LPL mass) increased significantly from 51 to 59 ng/dl (p<0.01 versus before benidipine hydrochloride administration), and the LDL/HDL motility ratio calculated from PAG disc electrophoresis decreased significantly (p<0.05 versus before benidipine hydrochloride administration). When patients were divided into a systolic hypertension group (systolic blood pressure ≥140 mmHg and diastolic blood pressure <90 mmHg) and non-systolic hypertension group (others), preheparin LPL mass was significantly lower in the systolic hypertension group, and the decrease in pulse pressure and increase in preheparin LPL mass were significantly greater in the systolic hypertension group. Stepwise regression analysis showed that low preheparin LPL mass at baseline was associated with a decrease in pulse pressure. Add-on benidipine hydrochloride therapy in elderly hypertensive patients with type 2 diabetes mellitus significantly decreases the LDL/HDL motility ratio and pulse pressure, and significantly increases preheparin LPL mass, in addition to improving blood pressure control. These findings suggest that combination therapy with benidipine hydrochloride and candesartan cilexetil may contribute to the suppression of arteriosclerosis and may be useful for elderly hypertensive patients with diabetes mellitus.
Case Report
  • Mitsunobu Kaneko, Mitsuo Ohni, Youichi Sugiyama, Shinjirou Mizukawa, K ...
    2006 年 13 巻 3 号 p. 158-161
    発行日: 2006年
    公開日: 2006/07/12
    ジャーナル フリー
    We report the autopsy of a 79-year-old Japanese woman with Dubin-Johnson syndrome accompanied by pneumonia, an abetalipoproteinemia-like lipid profile and acanthocytosis. On admission, physical examination of the patient revealed malnutrition. Blood tests revealed marked inflammatory changes and mild liver dysfunction. Chest X-ray indicated bilateral pneumonia. Total cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels were 89 mg/dL, 5 mg/dL and 6 mg/dL, respectively. Peripheral blood smears revealed numerous acanthocytes. Despite the administration of antibiotics and nutritional support, the patient died. Autopsy revealed a black liver, atrophy of fat tissue on the mesentery, and pneumonia with bilateral pleural effusion. We believe that the abetalipoproteinemia-like lipid profiles in this case were caused by malnutrition and the inflammatory changes rather than the direct effects of Dubin-Johnson syndrome. We base this conclusion on the following three findings: 1) the patient's lipid profile before hospitalization was in the normal range, 2) her serum LDL cholesterol and triglyceride levels gradually increased after nutritional support began, and 3) blood tests revealed marked inflammatory changes (C-reactive protein 9.0 mg/dL; interleukin-6 16.4 pg/mL). This case provides important information that enhances our understanding of lipid metabolism under conditions of malnutrition and inflammation.
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