Reduced alpha-lipoic acid synthase gene expression exacerbates atherosclerosis in diabetic apolipoprotein E-deficient mice.

Abstract

OBJECTIVES:

To study the effects of reduced lipoic acid gene expression on diabetic atherosclerosis in apolipoprotein E null mice (Apoe(-/-)).

METHODS AND RESULTS:

Heterozygous 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.

CONCLUSIONS:

Decreased 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.

• Authors: Xianwen Yi, Longquan Xu, Sylvia Hiller, Hyung-Suk Kim, Nobuyo Maeda
• Journal: Atherosclerosis (Atherosclerosis) Vol. 223 Issue 1 Pg. 137-43 (Jul 2012) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 22658261 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Apolipoproteins E
• Blood Glucose
• Ccl2 protein, mouse
• Chemokine CCL2
• Interleukin-6
• Cholesterol
• Glutathione Peroxidase
• Sulfurtransferases
• lipoic acid synthase
• Glutathione
• Glutathione Peroxidase GPX1
• Gpx1 protein, mouse

Topics

• Animals
• Aortic Diseases (blood, enzymology, etiology, genetics, pathology)
• Apolipoproteins E (deficiency, genetics)
• Apoptosis
• Atherosclerosis (blood, enzymology, etiology, genetics, pathology)
• Blood Glucose (metabolism)
• Chemokine CCL2 (genetics, metabolism)
• Cholesterol (blood)
• Diabetes Mellitus, Experimental (blood, complications)
• Disease Models, Animal
• Gene Expression Regulation
• Glutathione (blood)
• Glutathione Peroxidase (genetics, metabolism)
• Interleukin-6 (blood)
• Kidney (metabolism, pathology)
• Liver (metabolism, pathology)
• Macrophages (metabolism, pathology)
• Male
• Mice
• Mice, 129 Strain
• Mice, Knockout
• Oxidative Stress
• Sinus of Valsalva (enzymology, pathology)
• Sulfurtransferases (deficiency, genetics)
• Glutathione Peroxidase GPX1