Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression.
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 explo...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4028245?pdf=render |
| _version_ | 1818907822429044736 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Kevin J Woollard |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T22:01:14Z |
| format | Article |
| id | doaj.art-e69cf60fa3df4e66b1a4614d465c1b7b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T22:01:14Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e69cf60fa3df4e66b1a4614d465c1b7b2022-12-21T20:04:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9742210.1371/journal.pone.0097422Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression.Kevin J WoollardNatalie G LumsdenKaren L AndrewsAndrea ApricoEmma HarrisJennifer C IrvineAnn-maree JefferisLu FangPeter KanellakisAlex BobikJaye P F Chin-DustingSoluble 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.http://europepmc.org/articles/PMC4028245?pdf=render |
| spellingShingle | 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 Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression. PLoS ONE |
| title | Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression. |
| title_full | Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression. |
| title_fullStr | Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression. |
| title_full_unstemmed | Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression. |
| title_short | Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression. |
| title_sort | raised soluble p selectin moderately accelerates atherosclerotic plaque progression |
| url | http://europepmc.org/articles/PMC4028245?pdf=render |
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