The effect of genistein on aortic atherosclerosis was studied by immunohistochemistry with RAM-11 and HHF-35 antibodies and western blotting for matrix metalloproteinase-3 (MMP-3) in New Zealand White rabbits. After provocation of atherosclerosis with hyperlipidemic diet, the rabbits were divided as hyperlipidemic diet group (HD), normal diet group (ND) and hyperlipidemic plus genistein diet group (HD+genistein) for 4 and half months. The average cross sectional area of atherosclerotic lesion was 0.269 mm2 after provocation. The lesion was progressed by continuous hyperlipidemic diet (10.06 mm2) but was increased mildly by genistein (0.997 mm2), and decreased by normal diet (0.228 mm2). The ratio of macrophages to smooth muscle cells in the lesion was not changed by genistein supplementation. The western blotting showed reduction of MMP-3 expression in HD+genistein and ND groups than HD group. The inhibition of atherogenesis by genistein was might be due to improve the endothelial dysfunction rather than direct action on macrophages and/or smooth muscle cells in the lesion, since endothelial dysfunction by lipid peroxidation was the main atherogenic factor in the hypercholesterolemicrabbits. The genistein supplementation also suggests that it helps the stabilization of the atherosclerotic lesion by inhibition of MMP-3 expression.
Animals ; Aorta/pathology ; Arteriosclerosis/*drug therapy/pathology/*prevention & control ; Blotting, Western ; Diet, Atherogenic ; Genistein/*pharmacology ; Growth Inhibitors/*pharmacology ; Hypercholesterolemia/*drug therapy/pathology ; Macrophages/pathology ; Male ; Muscle, Smooth, Vascular/enzymology/pathology ; Rabbits ; Research Support, Non-U.S. Gov't ; Stromelysin 1/metabolism

BACKGROUNDControlling plasma glucose levels, blood pressure and lipid levels is proven to reduce the risk of vascular complications in patients with type 2 diabetes mellitus. This has prompted intensive multitherapy targeted at several macrovascular risk factors. Carotid intima-media thickness (cIMT) is a reliable measure of early atherosclerosis. We sought to determine whether a 6-month intensive mutiltherapy program resulted in better goal attainment than usual care and its effect on the development of cIMT among patients with newly diagnosed type 2 diabetes mellitus.

METHODSThe study randomly assigned 220 patients with newly diagnosed type 2 diabetes mellitus to intensive or traditional therapy groups. The clinical parameters, such as fasting plasma glucose, total cholesterol, triglyceride, blood pressure, body weight and insulin were assessed at the baseline and after the 6-month therapy. cIMT of the patients was also obtained.

RESULTSThe average levels of fasting plasma glucose, hemoglobin A1c, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the intensive group were significantly lower than those in the control group at the end of 6-month treatment. By 6 months, a higher proportion of patients in the intensive therapy group than in the control group attained goals for fasting plasma glucose (FPG), TC, LDL-C and hemoglobin A1c. With intensive multherapy the level of carotid intima-media thickness in the intensive therapy group was lower than that in the control group ((0.88 +/- 0.26) mm vs (0.96 +/- 0.22) mm, P < 0.01).

CONCLUSIONSThe evidence from this clinical trial demonstrates that intensive glucose, lipid and blood pressure control in patients with newly diagnosed type 2 diabetes is associated with diabetic macrovascular benefits. Intensive multitherapy allows more patients to achieve aims of control and may reduce macrovascular complications and delay disease progression.

Arteriosclerosis ; prevention & control ; Carotid Arteries ; pathology ; Diabetes Complications ; prevention & control ; Diabetes Mellitus, Type 2 ; drug therapy ; Drug Therapy, Combination ; Humans ; Hypoglycemic Agents ; administration & dosage ; Middle Aged ; Prospective Studies ; Tunica Intima ; pathology