Previously, one of the authors developed a noninvasive measurement method of acceleration and deceleration during the expansion process of the blood vessel wall under pulsatile pressure flow by measuring the strain rate of the blood vessel wall using a supersonic Doppler effect sensor aided by computer analysis (DPC method). In this paper, on the basis of the analysis of chaos theory, that is, the complexity of science, the unstable behavior of the blood vessel wall with an aneurysm was investigated by identifying the characteristic DPC wave forms induced by the onset and progression of aneurysm. These results showed that unstable dynamic behavior of the blood vessel wall occurs due to the progression of the aneurysm. Furthermore, using the theoretical analysis of chaos, this unstable behavior of the blood vessel wall was quantified and the fundamental principle of a noninvasive diagnostic method of the progressive degree of aneurysm was proposed.

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Objective: Several cohort studies have shown a link between serum C-reactive protein (CRP) and subsequent cardiovascular disease; however, the role of CRP as an independent risk factor remains controversial. We therefore investigated the association between CRP and sclerotic lesions of common carotid atherosclerosis.
Patients and Methods: We evaluated sclerotic lesions of common carotid arterial intima-media thickness (IMT) by ultrasonography in 139 men aged 67 ± 15 years and 201 women aged 75 ± 10 years. To investigate the relation between CRP and various confounding factors, subjects were divided into four groups based on the quartile of CPR.
Results: Carotid IMT values were significantly higher in groups with higher CRP (p=0.022). To identify the possible CRP level and risk factor interactions for IMT, multiple regression analysis for IMT was performed based on risk factors in subjects with a specific CRP level. It was shown that age, smoking status, systolic blood pressure (SBP) and LDL cholesterol were significantly associated with IMT in subjects in the lower CRP groups (CRP-1~CRP-3), and age, SBP and presence of diabetes mellitus in the highest CRP group (CRP-4). To further investigate whether the interaction between CRP and conventional risk factors could influence IMT, a general linear model demonstrated that interaction between CRP and the presence of diabetes mellitus (F=4.754 p=0.030) was significantly associated with IMT, in addition to sex, age, SBP, antihypertensive drug use, LDL cholesterol and HDL cholesterol.
Conclusions: This finding indicates that the association between CRP and IMT significantly differed between subjects with and without diabetes mellitus.

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The proliferation of vascular smooth muscle cells (VSMCs) can contribute to a variety of pathological states, including atherosclerosis and post-angioplasty restenosis. The p21^WAF1 cyclin-dependent kinase inhibitor regulates cell-cycle progression, senescence, and differentiation in injured blood vessels. Histone deacetylase (HDAC) inhibitors have shown utility in controlling proliferation in a wide range of tumor cell lines, possibly by inducing the expression of p21^WAF1. Our goal was to investigate the effect of trichostatin A (TSA), a specific and potent HDAC inhibitor, on the proliferation of vascular smooth muscle cells (VSMCs) isolated from rat thoracic aorta. TSA suppressed the HDAC activity of VSMCs in a dose-dependent manner and inhibited VSMC proliferation as demonstrated by cell number counting and the degree of [³H] thymidine incorporation. Further, TSA reduced the phosphorylation of Rb protein, a regulator of cell-cycle progression. TSA treatment also induced the expression of p21^WAF1 but not of p16^INK4, p27^KIP1 or p53. Finally, TSA inhibited HDAC activity of VSMCs from p21^WAF1 knock-out mice but had no effect on VSMC proliferation in these animals. In conclusion, TSA inhibits VSMC proliferation via the induction of p21^WAF1 expression and subsequent cell-cycle arrest with reduction of the phosphorylation of Rb protein at the G1-S phase.

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Background:Alanine-for-threonine substitution at codon 54 (A54T polymorphism) in the fatty acid-binding protein 2 gene (FABP2) has been associated with hypertriglyceridemia and insulin resistance. Impairment in the activity of delta 6 and 5 desaturases is also supposed to be a factor predisposing the development of insulin resistance syndrome.
Aim: We investigated the relationship between A54T polymorphism in FABP2 and the impairment of long-chain polyunsaturated fatty acid metabolism in obese children.
Methods: Thirty-two obese children participated. During the study, the children continued their habitual diet, which was documented in a 3-day food record using household measures. Anthropometry was performed, and serum lipid and fatty acid composition in plasma were analyzed. The polymorphism of codon 54 in the FABP 2 gene was analyzed.
Results: The allele frequency was 0.66 and 0.34 for Ala54 and Thr54, respectively. There were no significant differences in age, body mass index, fasting serum glucose, insulin or serum lipoproteins among the three polymorphism groups. These were also no significant differences in the intake of energy, the percentage of energy nutrients or in the dietary lipid composition. The content of arachidonic acid (AA) in plasma was lowest in Thr/Thr54 (p< 0.05). The indices of delta-6 desaturase (D6D) activity in Thr/Thr54 were significantly lower than in Thr/Ala54 or Ala/Ala54 (p< 0.05, p< 0.01, respectively).
Conclusions: In obese children, Thr/Thr54 of the FABP 2 gene is associated with impaired activation of D6D and reduced AA content. The results in the LCPUFA profile suggest that Thr/Thr54 may predispose the to development of insulin resistance.

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Objective: To clarify the effects of walking with a pedometer on metabolic parameters, including adiponectin (APN).
Methods: We recruited 44 male Japanese volunteers (age, 37 ± 9 yrs; body mass index (BMI), 24.2 ± 2.9 kg/m²; fasting plasma glucose (FPG), 96 ± 11 mg/dL; total cholesterol (TC) 190 ± 26 mg/dL; triglycerides (TG) 119 ± 80 mg/dL; HDL-C56 ± 14 mg/dL). Subjects were instructed to walk with a pedometer and record the number of steps they walked every day for 50 days. Serum adiponectin (APN) levels were measured by enzyme immunoassay. Treatment effects were examined by Wilcoxon's rank test.
Results: The average number of steps was 8211 ± 2084 per day. There were significant reductions in BMI, sBP, TG and TNF-α levels after 50 days, but no changes in adiponectin levels. We then divided the subjects into 2 groups according to the steps walked per day, namely, more than 8000 steps (MT group, n=22) and less than 8000 steps (LT group, n=22) and found that the reduction in TG and BP was observed only in the MT group.
Conclusions: Walking with a pedometer is effective for improving metabolic parameters, such as TG and blood pressure, but is not sufficient to increase adiponectin levels in Japanese men.

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To determine the prevalence of metabolic syndrome in the Japanese general population, we analyzed data from a nationwide survey conducted in 2000. According to the Japanese new diagnostic criteria for metabolic syndrome in 2005, we analyzed 3,264 people aged from 20 to 79 (men, 1,917; women, 1,347) from the total participants. The incidence of metabolic syndrome was 7.8%. Men had a higher incidence (12.1%) than women (1.7%). Most of the women satisfying the criteria were 50 years old or over, while the incidence in men started to rise from their 30s. When we applied the criteria of Adult Treatment Panel III, the incidence was about 3-fold higher. In this population visceral obesity was associated with metabolic abnormalities, such as higher LDL-cholesterol, triglyceride, glucose, and blood pressure and lower HDL-cholesterol. Thus we determined the incidence of metabolic syndrome and each metabolic abnormality in the Japanese general population in 2000 and found an association of visceral obesity with metabolic abnormalities. Intervention to reduce the incidence of metabolic syndrome in Japan is necessary to reduce the risk of cardiovascular disease.

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Objective: We examined various factors possibly related to metabolic syndrome, particularly focusing on nutritional assessment proteins such as retinol binding protein (RBP) and transthyretin (TTR), and remnant lipoproteins.
Materials and Methods: Fasting serum lipid was analyzed in 58 Japanese adult volunteers (33 men and 25 women, 42.5 ± 10.1 years old).
Results: The lipid profiles of the subjects were classified by lipoprotein polyacrylamide gel electrophoretic patterns into Types S (n=10), A (n=37), and N (n=11), according to the method described in Internal Medicine 42: 244, 2003. RBP and TTR were significantly higher in Type N than in Types S and A. In multivariate analysis, RBP was accounted for by remnant-like particle-triglyceride (RLP-TG), interleukin 6, body mass index and low-density lipoprotein (LDL)-cholesterol (adjusted R² =0.621). TTR was accounted for by lipoprotein(a), adiponectin and RLP-TG (adjusted R² =0.415). Malondialdehyde-LDL was significantly accounted for by LDL-cholesterol and RLP-cholesterol (adjusted R² =0.601). Lipoprotein(a) and LDL-cholesterol were independent variables for oxidized LDL antigen (adjusted R² =0.620). High-sensitivity C-reactive protein was accounted for by interleukin 6, immunoreactive insulin and oxidized LDL antigen (adjusted R² =0.361). Uric acid and body mass index were independent variables for adiponectin (adjusted R² =0.429).
Conclusion: RBP and TTR may be useful as convenient and simple clinical markers of overnutrition and possibly of metabolic syndrome.

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We investigated the lipid lowering and anti-atherosclerotic effects of atorvastatin in patients with hypercholesterolemia. Thirty patients were given atorvastatin 10 mg daily, and assessed for serum lipids, intima-media thickness (IMT), and brachial-ankle pulse wave velocity (ba-PWV) at the baseline, 6 months, and 12 months. Remnant-like particle-cholesterol (RLP-C), lipoprotein (a)(Lp(a)), and high-sensitivity C-reactive protein (hs-CRP) were measured in some patients at the baseline and at 6 months. Total cholesterol, triglyceride and low-density lipoprotein cholesterol were significantly decreased by 32%, 23% and 44% at 6 months, respectively, and these effects were sustained at 12 months. There was no change in high-density lipoprotein cholesterol. IMT at the baseline was 0.88 ± 0.16 mm and decreased to 0.76 ± 0.13 mm at 6 months, remaining at 0.75 ± 0.12 mm at 12 months. We did not observe any significant changes in ba-PWV. RLP-C and hs-CRP were significantly reduced from 7.3 ± 10.8 mg/dL to 4.3 ± 5.3 mg/dL and 0.075 ± 0.065 mg/dL to 0.039 ± 0.043 mg/dL at 6 months, respectively. There was no change in Lp(a). The observed decrease in IMT suggests that atorvastatin possibly improves atherosclerosis, in addition to the significant reduction of serum lipids.

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