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Wnt inducible soluble protein 1 (WISP-1) promotes VSMC migration and intimal thickening

Williams, H., Mill, C. A., Hulin-Curtis, Sarah, Johnson, J. L. and George, S. J. 2014. Wnt inducible soluble protein 1 (WISP-1) promotes VSMC migration and intimal thickening. Atherosclerosis 232 (2) , e2. 10.1016/j.atherosclerosis.2013.11.004

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Abstract

Vascular smooth muscle cell (VSMC) migration promotes coronary artery restenosis and vein graft failure. Therefore investigating factors involved in VSMC migration may enable us to improve treatments and therefore patient outcomes. We have previously shown that augmented Wnt2 expression occurred in and increased VSMC migration in vitro. This study aimed to further elucidate the mechanism of action of Wnt2. Addition of recombinant Wnt2 protein increased WISP-1 mRNA by 1.7±0.1 fold (p<0.05, n=4), while siRNA knockdown of Wnt-2 reduced WISP-1 mRNA (64.8±6.13%, p<0.05, n=3). Treatment with recombinant WISP-1, after a scratch-wound, significantly increased VSMC migration by 1.5±0.15 fold (p<0.05 n=4), while WISP-1 siRNA knockdown reduced migration by 36.0±11.8% (p<0.01 n=5). The effects of Wnt2 and WISP-1 were not additive, intimating that Wnt2 promotes VSMC migration via induction of WISP-1. We also saw that the location of Wnt2 and WISP-1 were significantly correlated in human diseased coronary arteries (r=0.647, r2=0.419, n=13 P<0.02). Using mouse carotid artery ligation we assessed the effect of reducing Wnt2 levels with Wnt2+/- mice; and elevation of plasma WISP-1 levels using tail-vein injection of WISP-1 adenovirus, on intimal thickening. Reduction in Wnt2 suppressed intimal thickening from 52.21±5.85% occlusion in controls to 37.16±8.2% in Wnt2+/- (p<0.05, n=14). Elevation of WISP-1 significantly increased intimal thickening compared to mice receiving control virus, (97±3% vs. 67±13% occlusion, p<0.05 n=11 and 9, respectively). This study demonstrates that Wnt2 promotes VSMC migration at least in part via WISP-1 and therefore inhibition of WISP-1 may provide a potential therapy for restenosis and vein graft failure.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Elsevier
ISSN: 0021-9150
Date of First Compliant Deposit: 12 April 2016
Date of Acceptance: 4 November 2013
Last Modified: 04 Jun 2017 09:00
URI: http://orca.cf.ac.uk/id/eprint/89099

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