title: Phospholipid transfer protein augments apoptosis in THP-1-derived macrophages induced by lipolyzed hypertriglyceridemic plasma.
abstract: OBJECTIVE
  Lipolysis of triglyceride-rich lipoproteins (TGRLPs) generates phospholipid-rich surface remnants and induces cytotoxic effects in adjacent vascular cells. We hypothesized that by integrating surface remnants into HDL, phospholipid transfer protein (PLTP) alleviates cytotoxicity.
  
  
  RESULTS
  To test this hypothesis and gain insight into cytotoxicity during the postprandial phase in vivo, we injected normo-TG and hyper-TG human volunteers after a standardized fat meal (postprandial sample) with heparin, thereby stimulating lipolysis (postprandial heparinized sample). Incubation of (primary) human macrophages and primary human endothelial cells with postprandial heparinized hyper-TG plasma induced pronounced cytotoxic effects that were dose dependent on the TG content of the sample. No such effects were seen with normo-TG and postprandial hyper-TG plasma. In vitro lipolysis of VLDL and chylomicrons indicated that both lipoprotein fractions can cause cytotoxicity. Interestingly, in experiments with THP-1-derived macrophages stably transfected with PLTP, PLTP substantially augmented both net phospholipid uptake and apoptotic cell death due to postprandial heparinized hyper-TG plasma. We observed that activation of caspase-3/7, poly-ADP-ribose polymerase, and enhanced bioactivity of acid sphingomyelinase may all contribute to this augmented apoptosis.
  
  
  CONCLUSIONS
  Our data show that lipolysis of TGRLPs and their remodelling by PLTP interact to disturb cellular phospholipid flux and intracellular signaling processes, ultimately leading to apoptosis in human macrophages and endothelial cells.
authors.affiliation: Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wehinger
authors.forename: Ivan
authors.initials: I
authors.lastname: Tancevski
authors.forename: Wilfried
authors.initials: W
authors.lastname: Schgoer
authors.forename: Philipp
authors.initials: P
authors.lastname: Eller
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hochegger
authors.forename: Maria
authors.initials: M
authors.lastname: Morak
authors.forename: Albin
authors.initials: A
authors.lastname: Hermetter
authors.forename: Andreas
authors.initials: A
authors.lastname: Ritsch
authors.forename: Josef R
authors.initials: JR
authors.lastname: Patsch
authors.forename: Bernhard
authors.initials: B
authors.lastname: Foeger
mesh_terms: D017209:Apoptosis; D001158:Arteries / Q000166:cytology; D001769:Blood / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D008066:Lipolysis; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D010767:Phosphorylcholine / Q000493:pharmacokinetics; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D014162:Transfection; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D008074:Lipoproteins; D049294:Phospholipid Transfer Proteins; D014280:Triglycerides; D010767:Phosphorylcholine; C038151:1,2-dipalmitoyl-sn-glycero-3-thiophosphocholine; D006493:Heparin; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D013108:Sphingomyelin Phosphodiesterase; D053148:Caspase 3; D053179:Caspase 7