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

Greig, F. H., Hutchison, L., Spickett, C. M. and Kennedy, S. (2015) Differential effects of chlorinated and oxidized phospholipids in vascular tissue: implications for neointima formation. Clinical Science, 128, pp. 579-592. (doi: 10.1042/CS20140578) (PMID:25524654)

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The presence of inflammatory cells and MPO (myeloperoxidase) in the arterial wall after vascular injury could increase neointima formation by modification of phospholipids. This 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) remodeling processes. Vascular injury was induced in C57BL/6 mice and high fat fed ApoE-/- mice by wire denudation and ligation of the left carotid artery. Neointimal and medial composition was assessed using immunohistochemistry and electrospray mass spectrometry. Primary rabbit aortic SMCs 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 vs. 0.83 ± 0.25 in C57BL/6 mice, n=3) and there was increased oxidized LDL (oxLDL) infiltration and elevated plasma MPO levels. Relative increases in lysophosphatidylcholines and unsaturated phosphatidylcholines were also observed in wire-injured ApoE-/- carotid arteries. Chlorinated lipids had no effect on VSMC proliferation, viability or migration while 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 vs. 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

Item Type:Articles
Glasgow Author(s) Enlighten ID:Kennedy, Professor Simon
Authors: Greig, F. H., Hutchison, L., Spickett, C. M., and Kennedy, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Clinical Science
Publisher:Portland Press Limited
ISSN (Online):1470-8736
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Clinical Science 128:579-592
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
495801Involvement of Chlorinated lipids in neointima formationSimon KennedyBritish Heart Foundation (BHF)FS/08/071/26212RI CARDIOVASCULAR & MEDICAL SCIENCES