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Publication Detail

Title: Gain and loss of function for glutathione synthesis: impact on advanced atherosclerosis in apolipoprotein E-deficient mice.

Authors: Callegari, Andrea; Liu, Yuhua; White, Collin C; Chait, Alan; Gough, Peter; Raines, Elaine W; Cox, David; Kavanagh, Terrance J; Rosenfeld, Michael E

Published In Arterioscler Thromb Vasc Biol, (2011 Nov)

Abstract: OBJECTIVE: Glutamate-cysteine ligase (GCL) is the rate-limiting step in glutathione synthesis. The enzyme is a heterodimer composed of a catalytic subunit, GCLC, and a modifier subunit, GCLM. We generated apolipoprotein E (apoE)-/- mice deficient in GCLM (apoE-/-/Gclm-/-) and transgenic mice that overexpress GCLC specifically in macrophages (apoE-/-/Gclc-Tg) to test the hypothesis that significantly altering the availability of glutathione has a measurable impact on both the initiation and progression of atherosclerosis. METHODS AND RESULTS: Atherosclerotic plaque size and composition were measured in the innominate artery in chow-fed male and female mice at 20, 30, 40, and 50 weeks of age and in the aortic sinus at 40 and 50 weeks of age. The apoE-/-/Gclm-/- mice more rapidly developed complex lesions, whereas the apoE-/-/Gclc-Tg mice had reduced lesion development compared with the littermate apoE-/- control mice. Transplantation of bone marrow from the apoE-/-/Gclm-/- and apoE-/-/Gclc-Tg mice into apoE-/- mice with established lesions also stimulated or inhibited further lesion development at 30 weeks posttransplant. CONCLUSION: Gain and loss of function in the capacity to synthesize glutathione especially in macrophages has reciprocal effects on the initiation and progression of atherosclerosis at multiple sites in apoE-/- mice.

PubMed ID: 21868708 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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