Ryuichi Sano

Effect of low density lipoprotein on DNA synthesis of cultured human arterial smooth muscle cells

Increased concentration of plasma low-density lipoprotein (LDL) is one of the risk factors in atherosclerosis. We studied how DNA synthesis of human arterial smooth muscle cells (SMC) was influenced in the culture added with or without small dose (25 micrograms of protein/ml) of LDL. LDL were ultracentrifugally obtained from normal subjects and diabetics. DNA synthesis was investigated at 6-h intervals during 36 h in the culture with or without LDL using [methyl-3H]thymidine. We found that DNA synthesis reached a maximum value at 24 h after addition of LDL. On the other hand sequential changes were not detectable in the culture without LDL addition. This effect of diabetic LDL was significantly (P less than 0.001) greater than that of normal LDL. These results suggested that LDL induces synchronization of the cultured SMC to synthesize DNA and diabetic LDL may play an atherogenic role more strongly than normal LDL in the arterial wall even in the normal range of LDL concentration.

Effect of Cilostazol on Lipid, Uric Acid and Glucose Metabolism in Patients with Impaired Glucose Tolerance or Type 2 Diabetes Mellitus

AbstractObjective: The aim of this study was to assess the effects of cilostazol on the metabolic profiles of serum lipids, uric acid and glycaemic control. Patients: This was a comparative study in a total of 112 patients with impaired glucose tolerance (IGT) or type 2 diabetes mellitus (DM) associated with hypertriglyceridaemia (fasting serum triglycerides ≥150 mg/dl) untreated with insulin, 81 of whom were evaluated for drug efficacy. Design: Patients enrolled were randomised to receive either cilostazol (group C) 200 mg/day or placebo (group P) [two tablets twice a day after breakfast and dinner] for 12 weeks according to a double-blind method. The study consisted of a 4-week run-in period (week -4 to week 0) followed by a 12-week administration period. Lipid parameters, uric acid and glycaemic control were measured at baseline (weeks -4, 0) and 4, 8 and 12 weeks after treatment. For each primary study variable, final assessment was based on the change observed after 12 weeks of administration relative to the baseline value obtained at week 0. Results: In group C, triglycerides (TG) decreased significantly (p < 0.05) from 238 ± 85 to 193 ± 105 mg/dl, but increased in group P. There was a significant (p < 0.05) difference between the two groups. High density lipoprotein-cholesterol (HDL-C) increased significantly (p < 0.05) from 39 ± 10 to 41 ± 11 mg/dl in group P. HDL-C in group C also increased but not significantly. When the results of one patient, whose HDL-C was over 100 mg/dl, were excluded, HDL-C in group C changed similarly to that in the subgroup (HDL-C level at baseline <50 mg/dl), which increased significantly (p < 0.001) from 38 ± 7 to 44 ± 10 mg/dl and the difference between groups P and C was also significant (p < 0.01). In group C, apolipoprotein B (apo B) decreased significantly (p < 0.01) from 155 ± 24 to 140 ± 28 mg/dl and apolipoprotein E (apo E) decreased significantly (p < 0.01) from 7.8 ± 1.9 to 6.7 ± 2.0 mg/dl. Uric acid also decreased significantly (p < 0.01) from 5.8 ± 1.5 to 5.3 ± 1.4 mg/dl in group C, but did not decrease significantly in group P, indicating a significant (p < 0.05) difference between the two groups. Glycaemic control (fasting plasma glucose level and HbA1c level) was not affected by either treatment. Abnormal laboratory findings were seen in 25.5% (14/55) of the patients in group P and in 14.3% (8/56) of those in group C, showing no significant difference between the two groups. Drug-related adverse events were observed in 7.3% (4/55) of the patients in group P and in 35.7% (20/56) of those in group C, indicating a significant (p < 0.001) difference between the two groups. Headache was the most frequent complaint (15 patients in group C). No increased bleeding tendencies or frank haemorrhage were noted in any patient. Conclusions: In IGT or type 2 DM patients with hypertriglyceridaemia, cilostazol 200mg effectively lowers TG and uric acid levels, and shows a potentially important effect in increasing HDL-C levels without significantly affecting glycaemic control. These results indicate that the clinical effect of cilostazol on lipid and uric acid metabolism is a beneficial effect that protects against atherosclerotic disease.