A085 Redox Homeostasis Controls Oxidized-Phospholipid-Induced-Pro-atherogenic Macrophage and T-cell Activation in Atherosclerotic Plaques or Peripheral Blood

Background: The role of oxidised phospholipid (Ox-PL) in cardiovascular disease (CVD) is not fully uncovered. Oxidised 1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphocholine (Ox-PAPC) is the most abundant phospholipid in mammalian cells. Atherosclerosis is the major cause of CVD, and Macrophages and T-cells are the most abundant cells in atherosclerotic plaques. Method: Macrophages and T-cells obtained from human peripheral blood or atherosclerotic plaques were stimulated with Ox-PAPC in absence or presence of mitochondrial reactive oxygen species inhibitor (mito tempo) or glutathione (GSH) inhibitor (BSO). The level of phosphatidylcholine, GSH or oxidised glutathione (GSSG) was measured from Plasma collected from healthy donors and patients with atherosclerotic plaques. Immune activation markers, heat shock protein 60 (HSP60), apoptosis, ROS production, and IL-1 beta were measured by flow cytometry and/or ELISA, and the GSH or GSSG and phosphatidylcholine were measured by colorimetric and fluorometric kit respectively Results: Ox-PAPC induced a pro-inflammatory type of T-cell activation but also induced apoptosis at a higher concentration. The Ox-PAPC-induced-immune-activation and apoptosis of T-cells was inhibited by the mito tempo, and the mito tempo or BSO inhibited inflammatory macrophage activation. Furthermore, the level of phosphatidylcholine, GSH and GSSG were significantly higher in atherosclerotic patients than the control group. Ox-PAPC-induced-macrophage induced such effect in vitro cell culture. Conclusion: The higher level of Ox-PL induced imbalance-redox homeostasis and thus higher level of GSH or GSSG could be a risk marker in atherosclerosis, and inhibition of such has possibility to maintain plaque stability.