title: Circulating biologically active oxidized phospholipids show on-going and increased oxidative stress in older male mice.
abstract: BACKGROUND
  The biologically active phospholipids Platelet-activating Factor (PAF) and oxidatively truncated phospholipids from chemical oxidation are increased in the circulation of rats subject to the oxidant stress of chronic ethanol ingestion. Potentially, circulating inflammatory and apoptotic phospholipids correlate to physiologic oxidative stress.
  
  
  RESULTS
  PAF and the common oxidatively truncated and biologically active phospholipid azelaoyl phosphatidylcholine (Az-PC) were significantly increased in the plasma of older mice, and in male mice. PAF and Az-PC are very rapidly cleared from the circulation, which was unaffected by age or sex. Platelets exposed to Az-PC display phosphatidylserine on their surface, and occlusive platelet carotid arterial thrombosis is enhanced by aging.
  
  
  CONCLUSIONS
  Biologically active phospholipids vary in the circulation, with the highest levels being found in older, male mice. Turnover of PAF and the biologically active Az-PC are rapid and are invariant with age and sex, so increased production accounts for the increased concentration and flux of both lipids. Platelets are exposed to plasma Az-PC that depolarizes their mitochondria to increase pro-thrombotic phosphatidylserine expression, and occlusive platelet thrombosis is enhanced in aged mice.
  
  
  CONCLUSIONS
  Oxidatively modified phospholipids are increased in the circulation during common, mild oxidant stresses of aging, or in male compared to female animals. Turnover of these biologically active phospholipids by rapid transport into liver and kidney is unchanged, so circulating levels reflect continuously increased production.
authors.affiliation: Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA; Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA; Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA; Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: mcintyt@ccf.org.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: McIntyre
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010743:Phospholipids / Q000097:blood / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: D010743:Phospholipids
keywords: Inflammation; Oxidized phospholipid; Pharmacokinetics; Platelet-activating Factor