title: Myeloid deletion of nuclear factor erythroid 2-related factor 2 increases atherosclerosis and liver injury.
abstract: OBJECTIVE
  To determine the impact of hematopoietic deletion of nuclear factor- (erythroid-derived 2) like 2 factor (Nrf2) on the development of atherosclerosis and liver injury in an obese, hypercholesterolemic mouse model.
  
  
  RESULTS
  Two-month-old male low-density lipoprotein receptor-deficient mice were lethally irradiated and transplanted with either wild type or Nrf2-deficient (Nrf2(-/-)) bone marrow cells. At 3 months of age, mice were placed on an obesogenic high-fat diet (HFD), high-cholesterol diet for 7 months. Despite no differences in body weight, body fat percentage, liver fat, plasma glucose, lipids, or insulin, the HFD-fed Nrf2(-/-) bone marrow recipients had increased proinflammatory vascular gene expression, a significant increase in atherosclerosis area (18% versus 28%; P=0.018) and lesion complexity, and a marked increase in liver fibrosis. The acceleration of vascular and liver injury may arise from enhanced macrophage migration, inflammation, and oxidative stress resulting from myeloid Nrf2 deficiency.
  
  
  CONCLUSIONS
  Myeloid-derived Nrf2 activity attenuates atherosclerosis development and liver inflammation and fibrosis associated with obesity. Prevention of oxidative stress in macrophage and other myeloid lineage cells may be an important therapeutic target to reduce inflammation-driven complications of obesity.
authors.affiliation: Division of Diabetes, Obesity and Lipids, The Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Collins
authors.forename: Anisha A
authors.initials: AA
authors.lastname: Gupte
authors.forename: Ruirui
authors.initials: R
authors.lastname: Ji
authors.forename: Maricela R
authors.initials: MR
authors.lastname: Ramirez
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Minze
authors.forename: Joey Z
authors.initials: JZ
authors.lastname: Liu
authors.forename: Magda
authors.initials: M
authors.lastname: Arredondo
authors.forename: Yuelan
authors.initials: Y
authors.lastname: Ren
authors.forename: Tuo
authors.initials: T
authors.lastname: Deng
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lyon
authors.forename: Willa A
authors.initials: WA
authors.lastname: Hsueh
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000453:epidemiology* / Q000378:metabolism / Q000503:physiopathology; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000502:physiology; D015897:Comorbidity; D004195:Disease Models, Animal; D017353:Gene Deletion; D006937:Hypercholesterolemia / Q000150:complications* / Q000453:epidemiology; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000378:metabolism / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000453:epidemiology; D018384:Oxidative Stress / Q000502:physiology; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D011973:Receptors, LDL