| First Author | Babaev VR | Year | 2011 |
| Journal | Free Radic Biol Med | Volume | 50 |
| Issue | 1 | Pages | 27-36 |
| PubMed ID | 20974251 | Mgi Jnum | J:167487 |
| Mgi Id | MGI:4868341 | Doi | 10.1016/j.freeradbiomed.2010.10.702 |
| Citation | Babaev VR, et al. (2011) Selective macrophage ascorbate deficiency suppresses early atherosclerosis. Free Radic Biol Med 50(1):27-36 |
| abstractText | 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, IL1beta, and IL6; and decreased lipopolysaccharide-stimulated NF-kappaB and antiapoptotic gene expression. These changes were associated with decreased expression of both the receptor for advanced glycation end products and HIF-1alpha, either or both of which could have been the proximal cause of decreased macrophage activation and apoptosis in ascorbate-deficient macrophages. |
