Jul 10, 2012

Copper chelation by tetrathiomolybdate inhibits vascular inflammation and atherosclerotic lesion development in apolipoprotein E-deficient mice

Atherosclerosis
Hao WeiBalz Frei

Abstract

Endothelial activation, which is characterized by upregulation of cellular adhesion molecules and pro-inflammatory chemokines and cytokines, and consequent monocyte recruitment to the arterial intima are etiologic factors in atherosclerosis. Redox-active transition metal ions, such as copper and iron, may play an important role in endothelial activation by stimulating redox-sensitive cell signaling pathways. We have shown previously that copper chelation by tetrathiomolybdate (TTM) inhibits LPS-induced acute inflammatory responses in vivo. Here, we investigated whether TTM can inhibit atherosclerotic lesion development in apolipoprotein E-deficient (apoE-/-) mice. We found that 10-week treatment of apoE-/- mice with TTM (33-66 ppm in the diet) reduced serum levels of the copper-containing protein, ceruloplasmin, by 47%, and serum iron by 26%. Tissue levels of "bioavailable" copper, assessed by the copper-to-molybdenum ratio, decreased by 80% in aorta and heart, whereas iron levels of these tissues were not affected by TTM treatment. Furthermore, TTM significantly attenuated atherosclerotic lesion development in whole aorta by 25% and descending aorta by 45% compared to non-TTM treated apoE-/- mice. This anti-atherogenic effect ...Continue Reading

Mentioned in this Paper

Oxidized Low Density Lipoprotein Measurement
Eosinophil
ISYNA1 gene
Biochemical Pathway
Hypocupremia
Necrosis
Vascular Inflammations
Xanthine
Entire Descending Aorta
Systemic Inflammatory Response Syndrome

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