Raised Soluble P-Selectin Moderately Accelerates Atherosclerotic Plaque Progression

• DOI: 10.1371/journal.pone.0097422
• Publication Date: 2014-05-20T20:23:55Z
• Authors: 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-D...
• Keywords: Mice, Knockout; 0301 basic medicine; Science; Macrophages; Q; R; Dietary Fats; Plaque, Atherosclerotic; 3. Good health; Disease Models, Animal; Mice; P-Selectin; 03 medical and health sciences; Apolipoproteins E; Medicine; Animals; Leukocyte Common Antigens; Chemokine CCL2; Research Article

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.