Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression

Kevin J. Woollard, Natalie G. Lumsden, Karen L. Andrews, Andrea Aprico, Emma Harris, Jennifer C. Irvine, Ann-maree Jefferis, Lu Fang, Peter Kanellakis, Alex Bobik, Jaye P. F. Chin-Dusting

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12 Citations (Scopus)

Abstract

Soluble P-selectin (sP-selectin), a biomarker of inflammatory related pathologies including cardiovascular and peripheral vascular diseases, also has pro-atherosclerotic effects including the ability to increase leukocyte recruitment and modulate thrombotic responses in vivo. The current study explores its role in progressing atherosclerotic plaque disease. Apoe -/- mice placed on a high fat diet (HFD) were given daily injections of recombinant dimeric murine P-selectin (22.5 μg/kg/day) for 8 or 16 weeks. Saline or sE-selectin injections were used as negative controls. In order to assess the role of sP-selectin on atherothrombosis an experimental plaque remodelling murine model, with sm22α-hDTR Apoe-/- mice on a HFD in conjunction with delivery of diphtheria toxin to induce targeted vascular smooth muscle apoptosis, was used. These mice were similarly given daily injections of sP-selectin for 8 or 16 weeks. While plaque mass and aortic lipid content did not change with sP-selectin treatment in Apoe-/- or SM22α-hDTR Apoe-/- mice on HFD, increased plasma MCP-1 and a higher plaque CD45 content in Apoe-/- HFD mice was observed. As well, a significant shift towards a more unstable plaque phenotype in the SM22α-hDTR Apoe-/- HFD mice, with increased macrophage accumulation and lower collagen content, leading to a lower plaque stability index, was observed. These results demonstrate that chronically raised sP-selectin favours progression of an unstable atherosclerotic plaque phenotype.

Original languageEnglish
Article numbere97422
Number of pages10
JournalPLoS ONE
Volume9
Issue number5
DOIs
Publication statusPublished - 20 May 2014
Externally publishedYes

Keywords

  • mouse models
  • atherosclerosis
  • collagens
  • apoptosis
  • blood plasma
  • inflammation
  • monocytes
  • white blood cells

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