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In the present study, we focus on the proliferation of human arterial smooth muscle cells (SMCs) from NIDDM patients (DM-SMCs) to clarify the reactivity to the growth factor(s) in fetal calf serum (FCS) and the factor(s) secreted by T-cells. The proliferation of DM-SMCs was significantly greater than SMCs from nondiabetic patients (nonDM-SMC). DM-SMC conditioned medium (DM-condMed) increased the growth of nonDM-SMCs. These results suggest that the growth factor is secreted from DM-SMCs as an autocrine system, which increases the proliferation of nonDM-SMCs. T-cells increased DNA synthesis of SMCs, and DM-SMCs strikingly reacted to T-cells. The present results support a function of T-cells in stimulating SMC growth. In conclusion, human arterial SMC proliferation is increased in diabetes in the same fashion as in experimentally induced diabetes in animals through responses to growth factors and an increased autocrine system. These results provide a mechanism for the increase in atherosclerotic disease in diabetes.

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This study was performed to investigate whether the plasma concentration of phosphatidylcholine hydroperoxide (PCOOH), which is a marker of oxidized stress in the blood, increased in cholesterol-fed rabbits, and fructose ingestion promoted this process and aggravated atherosclerosis. Male Japanese white rabbits (age: 12 weeks, and body weight: around 2.0 kg, n = 15) were divided into three groups, (1) a NN group as a normal control fed a standard diet (n = 5), (2) a CN group fed 1.0% cholesterol, and (3) a CF group given both 1.0% cholesterol and 10% fructose-containing tap water. During 8 weeks, plasma PCOOH levels increased significantly in the CN and CF groups compared to the NN group and fructose further raised the PCOOH level. The atherosclerosis was significantly promoted and the deposition of advanced glycation end products (AGEs) was marked in the CF group compared to the CN group. Fructose worsened the atheromatous lesions caused by cholesterol feeding. The mechanism is most likely through lipid peroxidation, which was increased by cholesterol feeding-induced hyperlipidemia, and the formation of AGEs. J Atheroscler Thromb, 2005; 12: 260-267.

(2), 91-99The effect of oral administration of taurine (3.2 g/day, 2 weeks) on the metabolism of lipids and bile acids was studied with healthy humans. Four male subjects were fed taurine. Another five male subjects were administered 1 g of cholesterol daily for two weeks and, at intervals of two weeks, cholesterol and taurine simultaneously. Serum lipoprotein and duodenal bile were analyzed. Oral administration of taurine resulted in the increase of taurine-conjugated bile acids. However, neither serum lipid nor biliary lipid composition was altered. Addition of taurine with cholesterol administration showed elevation of both the serum low density lipoprotein cholesterol level and the lithogenic index in bile. The ratio of glycine-to taurine-conjugated bile acids was changed from 4.1 to 0.63. The ratio of cholic acid/chenodeoxycholic acid was augmented from 0.57 to 0.81. The percentage of taurocholic acid, taurochenodexycholic acid and taurodeoxycholic acid were increased about 4-fold, 2.5-fold and 3-fold, respectively. Our results suggested that taurine administration alone did not influence the serum lipid level although taurine-conjugated bile acids were increased. The taurine intake would increase serum low density lipoprotein cholesterol and biliary cholesterol levels when excessive cholesterol is administered simultaneously.

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We investigated the effects of HMG-CoA reductase inhibitors (statins) on the activity and concentration of plasma cholesterol ester transfer protein (CETP) in 30 hypercholesterolemic patients. Patients were divided into three groups according to TaqIB polymorphism of the CETP gene. The activity (158 +/- 23% control, mean +/- SEM) and concentration (4.1 +/- 1.0 mg/l) of plasma CETP were significantly (p < 0.005) higher in the subjects with the B1B1 genotype than B2B2 genotype (106 +/- 25% and 2.5 +/- 1.1 mg/l, respectively). Plasma CETP activity and concentration levels in the B1B2 group were intermediate between those of the B1B1 and B2B2 groups, and significantly (p < 0.05) low compared with the B1B1 group.Both the activity and concentration of plasma CETP were positively correlated with the LDL-cholesterol concentration (r = 0.608, p < 0.0005 and r = 0.552, p < 0.005, respectively). The administration of statins significantly reduced not only the activity (p < 0.01) but also the concentration (p < 0.05) of plasma CETP in hypercholesterolemic patients. Taken together, we confirmed that statins would be effective in increasing HDL levels in Japanese B1B1 carriers, because of a lower concentration of HDL cholesterol and higher level of plasma CETP compared to the other genotypes. The genetic variation in the CETP gene may be one important factor in designing better treatments.