期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 50, 期 1, 页码 27-36出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2010.10.702
关键词
Antioxidants; Atherosclerosis; Macrophages; Ascorbic acid; Apolipoprotein E deficiency; Free radicals
资金
- NIH [DK050435, HL065709, HL057986, HL065405, HL086988, DK59637, GM 15431, DK020593]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL065405, R01HL086988, R01HL065709, R01HL057986] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK020593, R01DK050435, U24DK059637, P60DK020593] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P01GM015431, P50GM015431] Funding Source: NIH RePORTER
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 H2O2-induced mitochondrial dysfunction and apoptosis; decreased expression of genes for COX-2, IL1 beta, and IL6; and decreased lipopolysaccharide-stimulated NF-kappa B and antiapoptotic gene expression. These changes were associated with decreased expression of both the receptor for advanced glycation end products and HIF-1 alpha, either or both of which could have been the proximal cause of decreased macrophage activation and apoptosis in ascorbate-deficient macrophages. (C) 2010 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据