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

16 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Macrophages
Atherosclerosis
Apolipoproteins E
Apoptosis
Ascorbic Acid Deficiency
Gene Expression
Macrophage Activation
Cell Transplantation
Peritoneal Macrophages
Liver Transplantation
Lipopolysaccharides
Interleukin-6
Nutrition
Gene expression
Liver
Ascorbic Acid
Diet
Lipids
Genes
Chemical activation

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Selective macrophage ascorbate deficiency suppresses early atherosclerosis. / Babaev, Vladimir R.; Whitesell, Richard R.; Li, Liying; Linton, Macrae F.; Fazio, Sergio; May, James M.

In: Free Radical Biology and Medicine, Vol. 50, No. 1, 01.01.2011, p. 27-36.

Research output: Contribution to journalArticle

Babaev, Vladimir R. ; Whitesell, Richard R. ; Li, Liying ; Linton, Macrae F. ; Fazio, Sergio ; May, James M. / Selective macrophage ascorbate deficiency suppresses early atherosclerosis. In: Free Radical Biology and Medicine. 2011 ; Vol. 50, No. 1. pp. 27-36.
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