Selective macrophage ascorbate deficiency suppresses early atherosclerosis.

Babaev VR, Whitesell RR, Li L, Linton MF, Fazio S, May JM
Free Radic Biol Med. 2011 50 (1): 27-36

PMID: 20974251 · PMCID: PMC3014415 · DOI:10.1016/j.freeradbiomed.2010.10.702

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 H(2)O(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.

Copyright © 2010 Elsevier Inc. All rights reserved.

MeSH Terms (19)

Animals Apolipoproteins E Ascorbic Acid Ascorbic Acid Deficiency Atherosclerosis Cells, Cultured Disease Progression Female Genetic Predisposition to Disease Macrophages, Peritoneal Male Mice Mice, Inbred C57BL Mice, Knockout Organic Anion Transporters, Sodium-Dependent Organ Specificity Sodium-Coupled Vitamin C Transporters Symporters Time Factors

Connections (2)

This publication is referenced by other Labnodes entities:

Links