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Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Hydroxy alkenal phospholipids regulate inflammatory functions of endothelial cells
Ganesamoorthy Subbanagounder1, Yujin Deng, Christine Borromeo
1Department of Medicine/Cardiology, Center for the Health Sciences, Room 47-123, UCLA Medical Center, Los Angeles, CA 90095-1679, USA. gsubbanagounder@mednet.ucla.edu
A newly identified oxidized phospholipid, HOOA-PC, promotes monocyte recruitment in atherosclerosis by activating endothelial cells. This molecule increases inflammatory chemokines and influences leukocyte-endothelial interactions, highlighting its role in atherogenesis.
Area of Science:
- Cardiovascular Biology
- Lipid Biochemistry
- Immunology
Background:
- Monocyte recruitment is crucial in the development of atherosclerosis.
- Oxidized low-density lipoprotein (Ox-LDL) components activate endothelial cells, promoting inflammation.
- Previous research identified specific oxidized phospholipids in Ox-LDL affecting endothelial cell function.
Purpose of the Study:
- To identify and characterize novel oxidized phospholipids in Ox-PAPC.
- To investigate the role of 1-palmitoyl-2-(5-hydroxy-8-oxooct-6-enoyl)-sn-glycero-3-phosphocholine (HOOA-PC) in leukocyte-endothelial interactions.
- To determine the pro-inflammatory effects of HOOA-PC on endothelial cells.
Main Methods:
- Liquid chromatography/mass spectrometry (LC/MS) and tandem mass spectrometry (MS/MS) for identification.
- Synthesis of HOOA-PC for confirmation.
- In vitro assays using human aortic endothelial cells (HAECs) to assess monocyte binding and chemokine production.
- Analysis of E-Selectin expression.
Main Results:
- HOOA-PC was identified and confirmed as a component of Ox-PAPC.
- HOOA-PC dose-dependently increased monocyte adhesion to HAECs.
- HOOA-PC elevated levels of monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8).
- HOOA-PC modulated LPS-induced E-Selectin expression.
Conclusions:
- HOOA-PC is a novel pro-inflammatory oxidized phospholipid.
- HOOA-PC contributes to atherogenesis by regulating leukocyte-endothelial interactions.
- HOOA-PC acts as a free lipid to exert its effects on endothelial cells.
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