Differential effects of chlorinated and oxidized phospholipids in vascular tissue: implications for neointima formation

Fiona H. Greig, Lisa Hutchison, Corinne M. Spickett, Simon Kennedy

Research output: Contribution to journalArticle

Abstract

The presence of inflammatory cells and MPO (myeloperoxidase) in the arterial wall after vascular injury could increase neointima formation by modification of phospholipids. The present study investigates how these phospholipids, in particular oxidized and chlorinated species, are altered within injured vessels and how they affect VSMC (vascular smooth muscle cell) remodelling processes. Vascular injury was induced in C57BL/6 mice and high fat-fed ApoE-/- (apolipoprotein E) mice by wire denudation and ligation of the left carotid artery (LCA). Neointimal and medial composition was assessed using immunohistochemistry and ESI-MS. Primary rabbit aortic SMCs (smooth muscle cells) were utilized to examine the effects of modified lipids on VSMC proliferation, viability and migration at a cellular level. Neointimal area, measured as intima-to-media ratio, was significantly larger in wire-injured ApoE-/- mice (3.62±0.49 compared with 0.83±0.25 in C57BL/6 mice, n=3) and there was increased oxidized low-density lipoprotein (oxLDL) infiltration and elevated plasma MPO levels. Relative increases in lysophosphatidylcholines and unsaturated phosphatidylcholines (PCs) were also observed in wire-injured ApoE-/- carotid arteries. Chlorinated lipids had no effect on VSMC proliferation, viability or migration whereas chronic incubation with oxidized phospholipids stimulated proliferation in the presence of fetal calf serum [154.8±14.2% of viable cells at 1 μM PGPC (1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine) compared with control, n=6]. In conclusion, ApoE-/- mice with an inflammatory phenotype develop more neointima in wire-injured arteries and accumulation of oxidized lipids in the vessel wall may propagate this effect.

Original languageEnglish
Pages (from-to)579-592
Number of pages14
JournalClinical Science
Volume128
Issue number9
DOIs
Publication statusPublished - 1 May 2015

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Neointima
Apolipoproteins E
Blood Vessels
Phospholipids
Smooth Muscle Myocytes
Vascular Smooth Muscle
Vascular System Injuries
Inbred C57BL Mouse
Lipids
Carotid Arteries
Peroxidase
Cell Movement
Cell Survival
Cell Proliferation
Lysophosphatidylcholines
Phosphorylcholine
Phosphatidylcholines
Ligation
Arteries
Immunohistochemistry

Bibliographical note

This research was originally published in Clinical Science.Greig, F. H., Hutchison, L., Spickett, C. M., & Kennedy, S. (2015). Differential effects of chlorinated and oxidized phospholipids in vascular tissue: implications for neointima formation. Clinical Science, 128(9), 579-592; Published as Immediate Publication © the Biochemical Society

Cite this

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title = "Differential effects of chlorinated and oxidized phospholipids in vascular tissue: implications for neointima formation",
abstract = "The presence of inflammatory cells and MPO (myeloperoxidase) in the arterial wall after vascular injury could increase neointima formation by modification of phospholipids. The present study investigates how these phospholipids, in particular oxidized and chlorinated species, are altered within injured vessels and how they affect VSMC (vascular smooth muscle cell) remodelling processes. Vascular injury was induced in C57BL/6 mice and high fat-fed ApoE-/- (apolipoprotein E) mice by wire denudation and ligation of the left carotid artery (LCA). Neointimal and medial composition was assessed using immunohistochemistry and ESI-MS. Primary rabbit aortic SMCs (smooth muscle cells) were utilized to examine the effects of modified lipids on VSMC proliferation, viability and migration at a cellular level. Neointimal area, measured as intima-to-media ratio, was significantly larger in wire-injured ApoE-/- mice (3.62±0.49 compared with 0.83±0.25 in C57BL/6 mice, n=3) and there was increased oxidized low-density lipoprotein (oxLDL) infiltration and elevated plasma MPO levels. Relative increases in lysophosphatidylcholines and unsaturated phosphatidylcholines (PCs) were also observed in wire-injured ApoE-/- carotid arteries. Chlorinated lipids had no effect on VSMC proliferation, viability or migration whereas chronic incubation with oxidized phospholipids stimulated proliferation in the presence of fetal calf serum [154.8±14.2{\%} of viable cells at 1 μM PGPC (1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine) compared with control, n=6]. In conclusion, ApoE-/- mice with an inflammatory phenotype develop more neointima in wire-injured arteries and accumulation of oxidized lipids in the vessel wall may propagate this effect.",
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Differential effects of chlorinated and oxidized phospholipids in vascular tissue : implications for neointima formation. / Greig, Fiona H.; Hutchison, Lisa; Spickett, Corinne M.; Kennedy, Simon.

In: Clinical Science, Vol. 128, No. 9, 01.05.2015, p. 579-592.

Research output: Contribution to journalArticle

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AU - Greig, Fiona H.

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PY - 2015/5/1

Y1 - 2015/5/1

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