Leukaemia inhibitory factor retards the progression of atherosclerosis

Rolfe, Barbara E., Stamatiou, Steve, World, Cameron J., Brown, Lindsay, Thomas, Anita C., Bingley, John A., Worth, Nathalie F. and Campbell, Julie H. (2003) Leukaemia inhibitory factor retards the progression of atherosclerosis. Cardiovascular Research, 58 1: 222-230. doi:10.1016/S0008-6363(02)00832-5

Author Rolfe, Barbara E.
Stamatiou, Steve
World, Cameron J.
Brown, Lindsay
Thomas, Anita C.
Bingley, John A.
Worth, Nathalie F.
Campbell, Julie H.
Title Leukaemia inhibitory factor retards the progression of atherosclerosis
Journal name Cardiovascular Research   Check publisher's open access policy
ISSN 0008-6363
Publication date 2003
Sub-type Article (original research)
DOI 10.1016/S0008-6363(02)00832-5
Volume 58
Issue 1
Start page 222
End page 230
Total pages 9
Place of publication Amsterdam
Publisher Elsevier Science
Collection year 2003
Language eng
Subject C1
321003 Cardiology (incl. Cardiovascular Diseases)
Abstract Objective: Our previous studies showed that the pleiotropic cytokine leukaemia inhibitory factor (LIF) inhibits the de novo formation of experimental atherosclerotic lesions. The present study examined whether LIF also inhibits progression of pre-existing atheroma. Methods: Balloon angioplasty was performed on the right carotid arteries of 18 rabbits immediately before placing animals on a cholesterol-enriched diet. After 4 weeks, at which time the intima:media ratio (IN) was 0.99+/-0.12 (n=6), osmotic minipumps containing LIF (n=6) or saline control n=6) were inserted into the peritoneal cavity of each of the remaining rabbits for a further 4 weeks. Arteries were then harvested for analysis. Results: Continuous administration of LIF for the final 4 weeks of an 8-week cholesterol-enriched diet completely inhibited lesion progression in injured carotid arteries (I:M 1.05+/-0.16) compared with the saline-treated group at 8 weeks (1.62+/-0.13; P<0.05). Similarly in contralateral uninjured carotid arteries, LIF treatment prevented an increase in I:M from a baseline of 0.11+/-0.01 at 4 weeks to 0.15+/-0.02 at 8 weeks compared with 0.40+/-0.04 for the saline-treated group at 8 weeks (P<0.05). LIF reduced the number of macrophages in the neointima of uninjured arteries, but had no effect on the cellular composition of injured arteries. LIF treatment normalised smooth muscle-dependent vasoreactivity to phenylephrine and sodium nitroprusside in both injured and uninjured arteries. Expression and activity of inducible nitric oxide synthase (iNOS) were up-regulated in response to hypercholesterolemia with levels further increased following endothelial denudation. With LIF treatment, iNOS expression was increased in uninjured arteries but marginally reduced in injured arteries. LIF receptors were expressed in both uninjured and injured arteries, with LiF treatment having no significant effect on expression levels. Conclusion: LIF prevents progression of pre-formed atherosclerotic plaques, affecting lesion size and vascular reactivity. LIF treatment has differential effects within the artery wall, depending on the presence or absence of de-endothelialisation injury. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.
Keyword Cardiac & Cardiovascular Systems
Smooth Muscle
Vasoactive Agents
Nitric-oxide Synthase
Vascular Smooth-muscle
Arterial Injury
Cellular Proliferation
Endothelial Injury
Factor Lif
Q-Index Code C1

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Created: Wed, 15 Aug 2007, 02:30:47 EST