Effects of oxidized and chlorinated phospholipids on signaling pathways in endothelial cells

Norsyahida Mohd Fauzi, Emma Torrance, Thikryat Neamatallah, Ho Ka Ho, Corinne M. Spickett, Robin Plevin

Research output: Contribution to journalMeeting abstract

Abstract

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.
LanguageEnglish
Article numberP.13.7
Pages373
Number of pages1
JournalVascular Pharmacology
Volume56
Issue number5-6
DOIs
Publication statusPublished - May 2012

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Phospholipids
Endothelial Cells
Lipids
Phosphorylcholine
Blood Vessels
Chlorohydrins
Tumor Necrosis Factor-alpha
Atherosclerosis
E-Selectin
Wounds and Injuries
Myeloid Cells
Interleukin-8
Smooth Muscle Myocytes
Lipopolysaccharides
Monocytes
Microscopy
Cell Death
Anti-Inflammatory Agents
Western Blotting
Phosphorylation

Cite this

Fauzi, Norsyahida Mohd ; Torrance, Emma ; Neamatallah, Thikryat ; Ho, Ho Ka ; Spickett, Corinne M. ; Plevin, Robin. / Effects of oxidized and chlorinated phospholipids on signaling pathways in endothelial cells. In: Vascular Pharmacology. 2012 ; Vol. 56, No. 5-6. pp. 373.
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abstract = "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.",
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Effects of oxidized and chlorinated phospholipids on signaling pathways in endothelial cells. / Fauzi, Norsyahida Mohd; Torrance, Emma; Neamatallah, Thikryat; Ho, Ho Ka; Spickett, Corinne M.; Plevin, Robin.

In: Vascular Pharmacology, Vol. 56, No. 5-6, P.13.7, 05.2012, p. 373.

Research output: Contribution to journalMeeting abstract

TY - JOUR

T1 - Effects of oxidized and chlorinated phospholipids on signaling pathways in endothelial cells

AU - Fauzi, Norsyahida Mohd

AU - Torrance, Emma

AU - Neamatallah, Thikryat

AU - Ho, Ho Ka

AU - Spickett, Corinne M.

AU - Plevin, Robin

PY - 2012/5

Y1 - 2012/5

N2 - 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.

AB - 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.

U2 - 10.1016/j.vph.2011.08.182

DO - 10.1016/j.vph.2011.08.182

M3 - Meeting abstract

VL - 56

SP - 373

JO - Vascular Pharmacology

T2 - Vascular Pharmacology

JF - Vascular Pharmacology

SN - 1537-1891

IS - 5-6

M1 - P.13.7

ER -