Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wehinger, A; Tancevski, I; Schgoer, W; Eller, P; Hochegger, K; Morak, M; Hermetter, A; Ritsch, A; Patsch, JR; Foeger, B.
Phospholipid transfer protein augments apoptosis in THP-1-derived macrophages induced by lipolyzed hypertriglyceridemic plasma.
Arterioscler Thromb Vasc Biol. 2007; 27(4):908-915
Doi: 10.1161/01.ATV.0000259361.91267.8c
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- Co-Autor*innen der Med Uni Graz
- Eller Kathrin
- Eller Philipp
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- 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. Methods and 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Apoptosis -
- Arteries - cytology
- Blood - drug effects Blood - metabolism
- Caspase 3 - metabolism
- Caspase 7 - metabolism
- Cell Line -
- Endothelial Cells -
- Heparin - pharmacology
- Humans -
- Hypertriglyceridemia - blood
- Lipolysis -
- Lipoproteins - blood Lipoproteins - metabolism
- Macrophages - metabolism
- Monocytes -
- Phospholipid Transfer Proteins - genetics Phospholipid Transfer Proteins - metabolism
- Phosphorylcholine - pharmacokinetics
- Poly(ADP-ribose) Polymerases - metabolism
- Sphingomyelin Phosphodiesterase - metabolism
- Transfection -
- Triglycerides - blood Triglycerides - metabolism
- Umbilical Veins - cytology
- Find related publications in this database (Keywords)
- phospholipid transfer protein
- apoptosis
- human macrophages
- in vivo lipolysis
- hypertriglyceridemia
- triglyceride-rich lipoproteins