Aim: Retinoic acid-inducible gene-I (RIG-I) is one of the genes induced by interferon (IFN)-γ which plays an important role in atherosclerosis. The aim of this study is to examine if RIG-I is involved in atherosclerosis. Methods: The expression of RIG-I in atherosclerotic lesions in human aorta was examined by immunohistochemical analysis. The expression of RIG-I in THP-1 monocytic cell line or human monocyte-derived macrophages was studied by western blot and RT-PCR analyses. Results: Intense immunoreactivity for RIG-I was detected in intimal macrophages in atherosclerotic lesions. IFN-γ slightly enhanced the RIG-I expression in THP-1 cells. Treatment of the cells with phorbol 12-myristate 13-acetate, which induces the differentiation of the cells into macrophage-like cells, significantly enhanced the IFN-γ -induced RIG-I expression. IFN-γ also stimulated the expression of RIG-I in monocyte-derived macrophages. Conclusion: These results suggest that RIG-I may be involved in differentiation and activation of macrophages, playing a role in atherosclerosis.
Aim: Remnant lipoprotein is an emerging risk factor for coronary artery disease (CAD); however, the development of a specific remnant lipoprotein assay has struggled due to its heterogeneous nature. This study aimed to evaluate the clinical importance of a newly developed assay for remnant lipoprotein, RemL-C, in patients with CAD. Methods: This assay utilizes surfactant and phospholipase-D to selectively degrade and solubilize remnant lipoprotein. One hundred and sixty consecutive CAD patients who underwent coronary catheterization were recruited. Results: Remnant liporotein, RemL-C, was significantly higher in CAD patients (p< 0.001). Additionally, TG, hs-CRP, ICAM-1, VCAM-1, and homocysteine were significantly higher, but HDL-C and adiponectin were lower with LDL-C unchanged. Since RemL-C levels correlated with plasma TG levels, two subgroups, normotriglycedemic and normolipidemic CAD groups, were extracted. In both groups, RemL-C was still significantly higher than controls. HDL-C, but not RemL-C, was associated with the severity of CAD. RemL-C significantly correlated with TG-rich lipoproteins, in particular VLDL and IDL, when limited to normolipidemic CAD patients. Conclusion: Remnant lipoprotein, measured by RemL-C, was increased in CAD patients independent of TG levels, indicating impaired remnant lipoprotein metabolism in these patients. CAD severity was associated with HDL-C, but not with remnant lipoprotein, indicating differential roles of lipoproteins in the development of coronary atherosclerosis. This study therefore provides clinical significance to assess coronary risk by measuring RemL-C, particularly among patients with normal TG levels.
Aim: Aim of this study was to directly detect increased permeability of vascular lesions by magnetic resonance imaging. Methods: A novel contrast medium with a mean hydrodynamic diameter of 100 nm was prepared from monodispersed iron colloids incorporated into micelles of block copolymers composed of polyethylene glycol and polyamino acid. T2 mapping was applied to differentiate the minimal shortening of T2 relaxation time in balloon-injured rat carotid arteries. Results: The novel contrast medium accumulated in deendothelialized arteries. T2 relaxation times of injured and uninjured arteries were 50.6 ± 9.5 ms and 26.9 ± 2.4 ms, respectively (the mean ± SD, p< 0.01, n=5). The novel contrast medium, but not commercially available contrast media, shortened the T2 relaxation time of the injured artery to 35.5 ± 9.7 ms (p< 0.01, n=4). Conclusion: A novel iron contrast medium enhanced the lesions with increased permeability. The contrast medium in combination with T2 mapping may be useful to detect unstable atherosclerotic plaques.
Aim: We have investigated whether metabolic syndrome is a risk factor for carotid atherosclerosis also in normotensive or prehypertensive individuals. Methods: We analyzed the data from 851 subjects who had a blood pressure of less than 140/90 mmHg and were not taking antihypertensive medication. Metabolic syndrome was defined according to three different criteria: Japan criteria (Japan-MetS); those of the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATP III) (NCEP-MetS); and modified NCEP-ATP III criteria in which body mass index was used as a surrogate for waist circumference (modified NCEP-MetS). Results: Japan-MetS, NCEP-MetS, and modified NCEP-MetS were found, respectively, in 1%, 4%, and 4%, of women, and in 10%, 5%, and 9%, of men. After the adjustment for gender and age, the association between MetS and carotid atherosclerosis did not reach statistical significance. Conclusion: Although the number of enrolled subjects was relatively small, these data may further support the importance of controlling blood pressure within the optimal range for the purpose of preventing atherosclerosis in individuals with metabolic syndrome.
Aim: Carotid intima-media thickness (IMT) is a useful surrogate marker of cardiovascular disease and is associated with cardiac events. We investigated cross-sectionally the association between carotid intima-media thickness (IMT), confounding risk factors, and metabolic syndrome (MetS) using the modified Japanese criteria. Methods: Carotid IMT was evaluated on B-mode ultrasonography in 918 patients (394 men aged 66 ± 15 years and 524 women aged 72 ± 13 years). Results: Among our 918 patients, 74 (8.1%) had no metabolic abnormalities, 478 (52.1%) had a metabolic abnormality with neither type 2 diabetes or MetS, and 127 had MetS without diabetes. Of the patients with type 2 diabetes, 132 (14.4%) did not have MetS and 107 (11.7%) had both type 2 diabetes and MetS. The carotid IMT values in the four groups with any metabolic abnormalities were significantly greater than the IMT of the group with neither condition (p=0.001), respectively. In syndrome model, type 2 diabetes was significantly associated with carotid atherosclerosis (p= 0.006), but MetS was borderline significant. In the component model of MetS, there was a significant association with hypertension (p<0.001) and dyslipidemia (p=0.006). Multiple logistic regression analysis for carotid atherosclerosis compared to neither condition demonstrated that subjects with both MetS and diabetes (OR, 5.58; 95% CI, 2.64-11.8), those with type 2 diabetes without MetS (OR, 3.00; 95% CI, 1.45-6.22), and those with MetS without type 2 diabetes (OR, 2.58; 75% CI, 1.24-5.39) showed a higher odds ratio after adjustment for covariates. Conclusion: Even after taking into account each individual component of MetS, the clustering of visceral obesity with at least 2 of the 3 components, and diabetes are independently associated with increased carotid IMT. This suggests that the components of MetS and type 2 diabetes interact to affect vascular thickness synergistically.
Aim: The effects of pioglitazone hydrochloride monotherapy on abnormal lipid control were evaluated in Japanese patients with type 2 diabetes mellitus, comparing with glibenclamide monotherapy. Methods: Patients were randomly assigned to receive, once daily, pioglitazone hydrochloride, at 15 mg or 30 mg (n=46), or glibenclamide, at 1.25 mg or 2.5 mg (n=46). The 24-week study included patients with type 2 diabetes having high levels of triglyceride (TG). Results: Pioglitazone hydrochloride produced beneficial effects on dyslipidemia in patients with type 2 diabetes, compared with the baseline and the glibenclamide group, as demonstrated by increases in high-density lipoprotein cholesterol (HDL-C) levels and low-density lipoprotein cholesterol (LDL) particle size, a fall in TG levels, and an increased ratio of visceral to subcutaneous fat volumes (V/S). Pioglitazone hydrochloride reduced fasting serum insulin levels, with low fasting plasma glucose (FPG) and glycohemoglobin levels, compared to the baseline, suggesting an improvement of insulin resistance. Conclusion: As expected, glibenclamide reduced FPG levels through increased insulin secretion. Pioglitazone hydrochloride and glibenclamide were well tolerated. Pioglitazone hydrochloride improved dyslipidemia related to insulin resistance, whereas glibenclamide enhanced insulin secretion, with only a minor effect on lipid control, in Japanese patients with type 2 diabetes.
Aim: We experienced two pediatric siblings with homozygous familial hypercholesterolemia (FH) who received living donor liver transplantation (LDLT) from their parents who were heterozygous for FH. Methods: The elder brother presented orange cutaneous xanthomas and was diagnosed as homozygous FH at the age of one. The plasma lipid profile showed that his total cholesterol level was 898 mg/dL (23.2 mmol/L), LDL cholesterol level was 756 mg/dL (19.6 mmol/L) and triglyceride level was 60 mg/dL (0.7 mmol/L). There were no living donors with a normal LDL receptor in their family, and it was difficult to find a deceased donor in Japan; thus he underwent LDLT with his father as the donor. His sister was born 2 years after his LDLT. She underwent ABO-incompatible LDLT at the age of 2 with her mother as the donor. Results: The boy's liver function tests normalized immediately after transplantation, and his cholesterol has remained controlled at around 280 mg/dL (7.2 mmol/L), with HMG-CoA reductase inhibitor for 6 years after LDLT. The girl's cholesterol remained stable at around 280 mg/dL (7.2 mmol/L) under treatment with HMG-CoA reductase inhibitor two years after LDLT. At present, the four patients, including the two donors, are leading normal daily lives. Conclusion: Living-donor liver transplantation from a donor with heterozygous FH is a feasible indication for the treatment of homozygous FH.