Reduced alpha-lipoic acid synthase gene expression exacerbates atherosclerosis in diabetic apolipoprotein E-deficient mice |
| |
Authors: | Yi Xianwen Xu Longquan Hiller Sylvia Kim Hyung-Suk Maeda Nobuyo |
| |
Affiliation: | Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, 27599-7525, USA. xyi2000@med.unc.edu |
| |
Abstract: | ObjectivesTo study the effects of reduced lipoic acid gene expression on diabetic atherosclerosis in apolipoprotein E null mice (Apoe?/?).Methods and resultsHeterozygous lipoic acid synthase gene knockout mice (Lias+/?) crossed with Apoe?/? mice were used to evaluate the diabetic effect induced by streptozotocin on atherosclerosis in the aortic sinus of the heart. While diabetes markedly increased atherosclerotic plaque size in Apoe?/? mice, a small but significant effect of reduced expression of lipoic acid gene was observed in diabetic Lias+/?Apoe?/? mice. In the aortic lesion area, the Lias+/?Apoe?/? mice exhibited significantly increased macrophage accumulation and cellular apoptosis than diabetic Lias+/+Apoe?/? littermates. Plasma glucose, cholesterol, and interleukin-6 were also higher. These abnormalities were accompanied with increased oxidative stress including a decreased ratio of reduced glutathione/oxidized glutathione in erythrocytes, increased systemic lipid peroxidation, and increased Gpx1 and MCP1 gene expression in the aorta.ConclusionsDecreased endogenous lipoic acid gene expression plays a role in development of diabetic atherosclerosis. These findings extend our understanding of the role of antioxidant in diabetic atherosclerosis. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|