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The absence of macrophage Nrf2 promotes early atherogenesis
- Source :
- Cardiovascular Research. 98:107-115
- Publication Year :
- 2013
- Publisher :
- Oxford University Press (OUP), 2013.
-
Abstract
- Aims The loss of nuclear factor E2-related factor 2 (Nrf2) has been shown to protect against atherogenesis in apoE-deficient mice. The mechanism by which Nrf2 deficiency affords atheroprotection in this model is currently unknown, but combined systemic and local vascular effects on lesion macrophages have been proposed. We investigated the effect of bone marrow-specific loss of Nrf2 on early atherogenesis in low-density lipoprotein (LDL) receptor-deficient (LDLR−/−) mice, and assessed the effect of Nrf2 on cellular accumulation of modified LDLs and the expression of inflammatory markers in macrophages. Methods and results The effect of bone marrow-specific loss of Nrf2 on atherogenesis was studied using bone marrow transplantation of wild-type (WT) or Nrf2−/− bone marrow to LDLR−/− mice. Mice transplanted with Nrf2−/− bone marrow and fed a high-fat diet for 6 weeks exhibited significantly larger atherosclerotic lesions than WT bone marrow transplanted mice. Moreover, in thioglycollate-elicited Nrf2−/− macrophages, the uptake of acetylated and malondialdehyde-modified LDLs was increased in comparison with WT controls, with the concomitant increase in the expression of scavenger receptor A and toll-like receptor 4. In addition, the expression of pro-inflammatory monocyte chemoattractant protein-1 and interleukin-6 were increased in Nrf2−/− vs. WT macrophages. Conclusion Nrf2 deficiency specific to bone marrow-derived cells aggravates atherosclerosis in LDLR−/− mice. Furthermore, the loss of Nrf2 in macrophages enhances foam cell formation and promotes the pro-inflammatory phenotype.
- Subjects :
- medicine.medical_specialty
Pathology
NF-E2-Related Factor 2
Physiology
Biology
digestive system
environment and public health
Mice
Physiology (medical)
Internal medicine
medicine
Animals
Macrophage
Scavenger receptor
Receptor
Chemokine CCL2
Foam cell
Receptors, Scavenger
Macrophages
Monocyte
respiratory system
Atherosclerosis
Mice, Inbred C57BL
Cholesterol
Endocrinology
medicine.anatomical_structure
Receptors, LDL
LDL receptor
Female
lipids (amino acids, peptides, and proteins)
Bone marrow
Cardiology and Cardiovascular Medicine
Lipoprotein
Subjects
Details
- ISSN :
- 17553245 and 00086363
- Volume :
- 98
- Database :
- OpenAIRE
- Journal :
- Cardiovascular Research
- Accession number :
- edsair.doi.dedup.....f2519ffd4cc9b783348195accb171e30