Publications (2)12.24 Total impact
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Article: Prevention and treatment of macroangiopathy: focusing on oxidative stress.
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ABSTRACT: Oxidative stress has been proposed to be a major cause of atherosclerosis in diabetes. Endothelial dysfunction, common in diabetes, is considered a prerequisite for atherosclerosis. We evaluated whether alpha-lipoic acid (ALA) is an effective treatment for oxidative stress-induced endothelial dysfunction. Using high resolution ultrasound techniques, we evaluated flow mediated vasodilation (FMD) of the brachial artery in 13 young healthy men with transient hypertriglyceridemia (HTG) induced by intralipid infusion and in 11 postmenopausal type 2 diabetics before and after ALA treatment. We also measured superoxide anion formation in neutrophils as a maker of oxidative stress. FMD was decreased and superoxide anion formation was increased significantly following intralipid infusion in the young healthy men. ALA treatment, however, reversed the HTG-induced endothelial dysfunction and decreased the superoxide anion formation. Similarly, treatment with ALA increased FMD and decreased superoxide anion formation in the postmenopausal type 2 diabetics. In addition, the change in FMD was negatively correlated with superoxide anion formation in young healthy men and in postmenopausal type 2 diabetics (r = -0.54, -0.65, respectively). All P values were below 0.05. In conclusion, our results demonstrate that ALA treatment improves HTG- and diabetic-induced endothelial dysfunction, possibly due to the antioxidant effect of ALA.Diabetes Research and Clinical Practice 01/2005; 66 Suppl 1:S57-62. · 2.75 Impact Factor -
Article: Inhibitory effects of novel AP-1 decoy oligodeoxynucleotides on vascular smooth muscle cell proliferation in vitro and neointimal formation in vivo.
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ABSTRACT: Excessive proliferation of vascular smooth muscle cells (VSMCs) and neointimal formation are critical steps in the pathogenesis of atherosclerosis and restenosis after percutaneous transluminal angioplasty. In this study, we investigated the hypothesis that the activator protein-1 (AP-1) plays an important role in neointimal formation after vascular injury. A circular dumbbell AP-1 decoy oligodeoxynucleotide (CDODN) was developed as a novel therapeutic strategy for restenosis after angioplasty. This CDODN was more stable than the conventional phosphorothioate linear decoy ODN (PSODN) and maintained structural integrity on exposure to exonuclease III or serum. Transfection with AP-1 decoy ODNs strongly inhibited VSMC proliferation and migration, as well as glucose- and serum-induced expression of PCNA and cyclin A genes. Administration of AP-1 decoy ODNs in vivo using the hemagglutinating virus of Japan (HVJ)-liposome method virtually abolished neointimal formation after balloon injury to the rat carotid artery. Compared with PSODN, CDODN was more effective in inhibiting the proliferation of VSMCs in vitro and neointimal formation in vivo. Our results collectively indicate that AP-1 activation is crucial for the mediation of VSMC proliferation in response to vascular injury. Moreover, the use of stable CDODN specific for AP-1 activity in combination with the highly effective HVJ-liposome method provides a novel potential therapeutic strategy for the prevention of restenosis after angioplasty in humans.Circulation Research 07/2002; 90(12):1325-32. · 9.49 Impact Factor
