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Abstract
Atherosclerosis is a chronic inflammatory disease that is a leading cause of death and illness worldwide. Growing evidence suggests that oxidized low-density lipoprotein (OxLDL), particularly oxidized phospholipids (OxPL), plays a critical role in the pathogenesis of atherosclerosis. Mounting evidence has implicated toll-like receptors (TLRs) and scavenger receptor CD36 in playing a role in the progression of many inflammatory diseases, including atherosclerosis. POVPC (1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine) is an oxidized phospholipid found in OxLDL. It has pro-inflammatory effects on macrophages (MAC) that promote inflammatory diseases. However, the mechanism by which it does this is not well understood. OxPLs include a heterogeneous group of oxidation products and many of them are unstable. In order to study inflammatory effects on MAC, we developed a synthetic POVPC-peptide adduct at the sn-2 side chain, which is water soluble, stable, not prone to further oxidation and highly bioactive. We show that the POVPC-peptide mediates inflammatory gene expression of IL-1, TNF-, MIP-2, in MACs via TLRs 2/1 and co-receptor CD36. Understanding the mechanisms and role of POVPC in mediating MAC inflammation could provide insights into the role of OxPLs in inflammation and atherosclerosis, and could lead to novel therapies to inhibit these effects.
