The Japan Atherosclerosis Society (JAS) guidelines for the prevention of atherosclerotic diseases, proposing management for LDL cholesterol as the primary target, have successfully contributed to the prevention of cardiovascular events; however, recently, the impact of hypertriglyceridemia as an additional cardiovascular risk has become understood, especially in light of the rise in obesity, metabolic syndrome, and diabetes in the Japanese population. Rather than waiting to obtain conclusive domestic data confirming that hypertriglyceridemia is a cardiovascular risk factor and that its management is efficacious, we propose guidelines for hypertriglyceridemia using non-HDL cholesterol as a second target.
Aim: Despite the possible overall health benefits of a vegetarian diet, research about the nutritional characteristics of Japanese vegetarians is small. Our objective was to investigate the nutritional characteristics of Japanese vegetarians compared with Japanese non-vegetarians. Methods: The dietary intake, anthropometric and biochemical status of 75 middle-aged Japanese vegetarians (JV, 20 men and 55 women) were compared with those of 50 age- and sex- matched middle-aged Japanese non-vegetarians (JNV, 32 men and 18 women) in a cross-sectional study. Results: JV men had significantly higher calcium, iron (p<0.001) and dietary fiber (p<0.01), and significantly lower vitamin B12, cholesterol, animal fat intake and percentage of energy as animal protein (p<0.01) than JNV men. In addition, JV men had significantly lower body mass index (p<0.05), diastolic blood pressure (p<0.001), systolic blood pressure (p<0.01), aspartate transaminase, alanin transaminase (p<0.05) and serum triacylglyceride (p<0.001) than JNV men. JV women had significantly lower systolic pressure and serum triacylglyceride (p<0.05) than JNV women. Conclusions: JV men and women had better nutritional characteristics than JNV men and women from the standpoint of lifestyle-related diseases.
Aim: Oxysterols are found in high concentrations in advanced atherosclerotic plaques and are considered as an important factor in the development of vascular calcification. The purpose of this study was to investigate the effect of 7-ketocholesterol (7kc), a major oxysterol in plaques, on in vitro arterial calcification. Methods: Bovine vascular smooth muscle cells (VSMCs) were cultured with inorganic phosphate (Pi) in the presence or absence of 7kc. Calcium deposition was determined by Calcium C-test Wako and von Kossa staining. Phenotypic change was evaluated by mRNA expression using semi-quantitative reverse transcription-polymerase chain reaction. Cell apoptosis was determined by in situ DNA fragmentation assay. Results: 7kc significantly enhanced the calcium deposition, phenotypic change of VSMCs, and apoptosis in the presence of Pi. Treatment with risedronate, a bisphosphonate, or Y-27632, an Rho kinase inhibitor, completely or partially prevented the effects induced by 7kc in the presence of Pi, respectively. Conclusion: These results suggest that 7kc, a major oxysterol, significantly accelerates vascular calcification in the presence of Pi via the mevalonate pathway and Rho-ROCK signaling pathway. Our present data provide beneficial information on the development of a therapeutic approach for arterial calcification, especially in patients with a mineral imbalance, including hypocalcaemia, hyperphosphatemia, and hypercholesterolemia.
Aim: Lipoprotein lipase protein exists in preheparin serum (preheparin LpL mass), even though lipoprotein lipase activity is rarely detected. Recent clinical studies have clarified that low preheparin LpL mass concentration is an important coronary risk factor. The aim of this study was to clarify the effect of telmisartan, which is an angiotensin II receptor antagonist with partial peroxisome proliferator-activated receptor-γ agonist activity, on preheparin LpL mass concentration in the serum of patients with hypertension. Methods: Fifty untreated hypertensive patients were treated with telmisartan 40 mg/day for 12 weeks and the subjects were divided into two groups by their mean value of preheparin LpL mass concentration at baseline (cut-off level: Male 55 ng/mL, Female 65 ng/mL). Results: Before telmisartan therapy, low preheparin LpL mass concentration was closely associated with the pathogenesis of insulin resistance and the presence of coronary atherosclerosis. Preheparin LpL mass concentration significantly increased after telmisartan therapy in subjects with a low preheparin LpL mass concentration (baseline/12 weeks after, 46 ± 12 ng/mL/54 ± 14 ng/mL, p=0.001). Conclusion: This finding indicated that telmisartan could prevent the occurrence of coronary events in subjects with hypertension by increasing the preheparin LpL mass concentration.
Aim: The effects of statin on small dense low-density lipoprotein cholesterol (sd-LDL-C) and remnant-like particle cholesterol (RLP-C) levels in heterozygous familial hypercholesterolemia (FH) have not been examined. This study aimed to clarify the effects of statin on sd-LDL-C and RLP-C levels in heterozygous FH. Methods: Seventeen patients with heterozygous FH were randomly assigned to 2 mg/day pitavastatin or 10 mg/day atorvastatin. At baseline and 12 weeks after treatment with statin, we measured sd-LDL-C and RLP-C levels. Results: Sd-LDL-C levels significantly decreased from 43 ± 24 to 16 ± 10 mg/dL (−63%, p=0.001) in the pitavastatin group, and from 44 ± 17 to 19 ± 10 mg/dL (−55%, p<0.001) in the atorvastatin group. RLP-C levels decreased from 8.4 ± 2.8 to 6.6 ± 2.7 mg/dL (−16%, p=0.156) in the pitava-statin group, and from 9.8 ± 4.7 to 5.9 ± 5.4 mg/dL (−45%, p=0.044) in the atorvastatin group. There were no significant differences in percent changes of sd-LDL-C (p=0.370) and RLP-C levels (p=0.097) between the two groups. Conclusions: Sd-LDL-C measured by the heparin-magnesium precipitation method and RLP-C levels in heterozygous FH were decreased by 12 weeks of statin therapy. Statin might have additional anti-atherogenic effects by reducing not only LDL-C but also sd-LDL-C and RLP-C.
Aim: Previous reports indicate that serum lipoprotein lipase mass levels (LPL mass) and common carotid artery intima-media thickness (CCA-IMT) are independent predictors of atherosclerotic diseases. The aim of this study was to examine the effects of combination therapy of sulfonylurea and acarbose on LPL mass and CCA-IMT. Methods: Eighty-four patients with type 2 diabetes mellitus, who were treated with only sulfonylureas and showed CCA-IMT of more than 0.9 mm at baseline, were selected and randomly divided into two groups. One group was administered acarbose 300 mg/day for 12 months (acarbose group, n=41), and the other group was not administered acarbose (non-acarbose group, n=43). Results: After 12 months, a significant increase in LPL mass and a significant decrease in CCA-IMT were observed in the acarbose group (1.024 to 0.964 mm), but no significant changes were observed in the non-acarbose group. In a subgroup analysis of patients with HbA1c improved by 0.5% or more, the increase of LPL mass and decrease of CCA-IMT was significantly greater in the acarbose group than in the non-acarbose group although the changes in HbA1c were similar in two groups. Conclusions: We concluded that reducing postprandial hyperglycemia might increase LPL mass levels and might be useful to prevent macroangiopathy in type 2 diabetic patients treated by sulfonylurea.
Background: We recently reported that the A252G polymorphism of the Lymphotoxin-alpha (LTA) gene, a member of the tumor necrosis factor family, is strongly related with the onset of acute myocardial infarction; however, the roles of LTA in the development of atherosclerosis remain unclear. Methods and Results: Changes in gene expression profile in cultured human umbilical vein (HUVEC) and coronary artery endothelial cells (HCAEC) treated with LTA were analyzed with high density oligonucleotide arrays comprised of 8,500 genes. LTA stimulation at 10 ng/mL for 2 hours profoundly induced gene expression associated with signal transduction, cell adhesion and chemoattraction, such as the nuclear factor of kappa light polypeptide gene enhancer in B-cells (NFkB), endothelial adhesion molecule 1 (E-Selectin), vascular cell adhesion molecule 1 (VCAM1), and monocyte chemotactic protein 1 (MCP1) (2.6, 55.7, 45.3 and 2.8 fold in HUVEC, and 2.6, 137.2, 64.0 and 13.0 fold in HCAEC, respectively). Quantitative real-time reverse transcriptase-polymerase chain reaction analysis confirmed that LTA increased the expressions of E-Selectin and VCAM1 in a dose-dependent manner both in HUVEC and HCAEC. Conclusion: LTA increased the expression of various genes involved in the process of atherosclerosis or inflammation in human endothelial cells, suggesting the roles of LTA in the development of atherosclerosis.