Selective macrophage ascorbate deficiency suppresses early atherosclerosis

Vladimir R. Babaev, Richard R. Whitesell, Liying Li, Macrae F. Linton, Sergio Fazio, James M. May

    Research output: Contribution to journalArticle

    18 Scopus citations

    Abstract

    To test whether severe ascorbic acid deficiency in macrophages affects progression of early atherosclerosis, we used fetal liver cell transplantation to generate atherosclerosis-prone apolipoprotein E-deficient (apoE -/-) mice that selectively lacked the ascorbate transporter (SVCT2) in hematopoietic cells, including macrophages. After 13 weeks of chow diet, apoE-/- mice lacking the SVCT2 in macrophages had surprisingly less aortic atherosclerosis, decreased lesion macrophage numbers, and increased macrophage apoptosis compared to control-transplanted mice. Serum lipid levels were similar in both groups. Peritoneal macrophages lacking the SVCT2 had undetectable ascorbate; increased susceptibility to H2O 2-induced mitochondrial dysfunction and apoptosis; decreased expression of genes for COX-2, IL1β, and IL6; and decreased lipopolysaccharide-stimulated NF-κB and antiapoptotic gene expression. These changes were associated with decreased expression of both the receptor for advanced glycation end products and HIF-1α, either or both of which could have been the proximal cause of decreased macrophage activation and apoptosis in ascorbate-deficient macrophages.

    Original languageEnglish (US)
    Pages (from-to)27-36
    Number of pages10
    JournalFree Radical Biology and Medicine
    Volume50
    Issue number1
    DOIs
    StatePublished - Jan 1 2011

    Keywords

    • Antioxidants
    • Apolipoprotein E deficiency
    • Ascorbic acid
    • Atherosclerosis
    • Free radicals
    • Macrophages

    ASJC Scopus subject areas

    • Biochemistry
    • Physiology (medical)

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