More than 25 years ago, it was proposed that the inflammatory disease atherosclerosis arises as a response of vascular wall to endothelial injury and many studies showed that this injury could be due to endothelial apoptosis. As a result of vascular inflammation, oxidized and chlorinated lipids are generated and are thought to be a primary risk factor in the progression of atherosclerosis. There are extensive studies on the biological effects of oxidized phospholipids (oxPAPC) in vascular cells including smooth muscle cells and endothelial cells and more recently, analysis of individual oxidized species, 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC). For instance, oxPAPC has been shown to induce production of IL-8, MCP-1 /MIP-2 and expression of E-selectin in myeloid and endothelial cells (Erridge et al., 2007), whilst POVPC increases monocyte binding to endothelial cells, by inducing the surface expression of connecting segment-1 domain of fibronectin (Leitinger et al., 1999). Oxidized phospholipids can also have anti-inflammatory effects; OxPAPC prevents TLR-2 and 4 activation by lipopolysaccharide and Pam3CSK4 (Erridge et al., 2008). In comparison however, little is known about effects of chlorinated lipids on vascular function. To investigate this, the effect of chlorinated lipids upon NFkB and MAP kinase signaling was studied in HUVECs. Oxidized phospholipids such as oxPAPC, PGPC and POVPC (5–50 μM) and chlorinated lipids including SOPC chlorohydrins and 2-Chlorohexadecanal (5–50 μM) were assessed for IκB-α degradation and phosphorylation of ERK, p38 and JNK, by Western blotting. Results showed that SOPC chlorohydrin and 2-chlorohexadecanal alone did not induce phoshorylation of NFkB and MAPK nor inhibit IκB-α degradation induced by LPS and TNF-α. In contrast, oxidized phospholipids such as oxPAPC inhibited IκB-α degradation induced by LPS but not TNF-α, a result which is in agreement with a previous study (Bochkov et al., 2002). Preliminary studies used microscopy to investigate the effect of oxidized and chlorinated lipids on cellular integrity of endothelial cells. Interestingly, treatment of chlorinated lipids (50–100 μM) induced cell death and this was potentiated in the presence of TNF-α. These results demonstrate that chlorinated lipids may produce pro-atherogenic effects but do not appear to regulate endothelial cell function in the same way as oxidized phospholipids.
Fauzi, N. M., Torrance, E., Neamatallah, T., Ho, H. K., Spickett, C. M., & Plevin, R. (2012). Effects of oxidized and chlorinated phospholipids on signaling pathways in endothelial cells. Vascular Pharmacology, 56(5-6), 373. [P.13.7]. https://doi.org/10.1016/j.vph.2011.08.182