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 language | English (US) |
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Pages (from-to) | 27-36 |
Number of pages | 10 |
Journal | Free Radical Biology and Medicine |
Volume | 50 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2011 |
Externally published | Yes |
Keywords
- Antioxidants
- Apolipoprotein E deficiency
- Ascorbic acid
- Atherosclerosis
- Free radicals
- Macrophages
ASJC Scopus subject areas
- Biochemistry
- Physiology (medical)