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 journalArticlepeer-review

18 Scopus citations


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
Issue number1
StatePublished - Jan 1 2011
Externally publishedYes


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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


Dive into the research topics of 'Selective macrophage ascorbate deficiency suppresses early atherosclerosis'. Together they form a unique fingerprint.

Cite this