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Chronic, not acute, skin-specific inflammation promotes thrombosis in psoriasis murine models

Overview of attention for article published in Journal of Translational Medicine, December 2015
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Title
Chronic, not acute, skin-specific inflammation promotes thrombosis in psoriasis murine models
Published in
Journal of Translational Medicine, December 2015
DOI 10.1186/s12967-015-0738-z
Pubmed ID
Authors

Jackelyn B. Golden, Yunmei Wang, Yi Fritz, Doina Diaconu, Xiufen Zhang, Sara M. Debanne, Daniel I. Simon, Thomas S. McCormick, Nicole L. Ward

Abstract

Psoriasis patients exhibit an increased risk of atherothrombotic events, including myocardial infarction and stroke. Clinical evidence suggests that psoriasis patients with early onset and more severe disease have the highest risk for these co-morbidities, perhaps due to the extent of body surface involvement, subsequent levels of systemic inflammation, or chronicity of disease. We sought to determine whether acute or chronic skin-specific inflammation was sufficient to promote thrombosis. We used two experimental mouse models of skin-specific inflammation generated in either an acute (topical Aldara application onto wild-type C57Bl/6 mice for 5 days) or chronic (a genetically engineered K5-IL-17C mouse model of psoriasiform skin inflammation) manner. Arterial thrombosis was induced using carotid artery photochemical injury (Rose Bengal-green light laser) and carotid artery diameters were measured post-clot formation. We also examined measures of clot formation including prothrombin (PT) and activated partial thromboplastin time (aPTT). Skin inflammation was examined histologically and we profiled plasma-derived lipids. The number of skin-draining lymph-node (SDLN) and splenic derived CD11b(+)Ly6C(high) pro-inflammatory monocytes and CD11b(+)Ly6G(+) neutrophils was quantified using multi-color flow cytometry. Mice treated with topical Aldara for 5 days had similar carotid artery thrombotic occlusion times to mice treated with vehicle cream (32.2 ± 3.0 vs. 31.4 ± 2.5 min, p = 0.97); in contrast, K5-IL-17C mice had accelerated occlusion times compared to littermate controls (15.7 ± 2.1 vs. 26.5 ± 3.5 min, p < 0.01) while carotid artery diameters were similar between all mice. Acanthosis, a surrogate measure of inflammation, was increased in both Aldara-treated and K5-IL-17C mice compared to their respective controls. Monocytosis, defined as elevated SDLN and/or splenic CD11b(+)Ly6C(high) cells, was significantly increased in both Aldara-treated (SDLN: 3.8-fold, p = 0.02; spleen: 2.0-fold, p < 0.01) and K5-IL-17C (SDLN: 3.4-fold, p = 0.02; spleen: 3.5-fold, p < 0.01) animals compared to controls while neutrophilia, defined as elevated SDLN and/or splenic CD11b(+)Ly6G(+) cells, was significantly increased in only the chronic K5-IL-17C model (SDLN: 11.6-fold, p = 0.02; spleen: 11.3-fold, p < 0.01). Plasma-derived lipid levels, PT and aPTT times showed no difference between the Aldara-treated mice or the K5-IL-17C mice and their respective controls. Chronic, but not acute, skin-specific inflammation was associated with faster arterial thrombotic occlusion. Increased numbers of splenic and SDLN monocytes were observed in both acute and chronic skin-specific inflammation, however, increased splenic and SDLN neutrophils were observed only in the chronic skin-specific inflammation model. Understanding the cellular response to skin-specific inflammation may provide insights into the cellular participants mediating the pathophysiology of major adverse cardiovascular events associated with psoriasis.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 26 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 19%
Other 4 15%
Unspecified 3 12%
Professor 3 12%
Student > Bachelor 2 8%
Other 3 12%
Unknown 6 23%
Readers by discipline Count As %
Medicine and Dentistry 6 23%
Unspecified 3 12%
Neuroscience 2 8%
Immunology and Microbiology 2 8%
Nursing and Health Professions 1 4%
Other 5 19%
Unknown 7 27%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 December 2015.
All research outputs
#3,277,108
of 6,777,408 outputs
Outputs from Journal of Translational Medicine
#910
of 1,636 outputs
Outputs of similar age
#145,987
of 287,817 outputs
Outputs of similar age from Journal of Translational Medicine
#53
of 84 outputs
Altmetric has tracked 6,777,408 research outputs across all sources so far. This one is in the 29th percentile – i.e., 29% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,636 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 13th percentile – i.e., 13% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 287,817 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 84 others from the same source and published within six weeks on either side of this one. This one is in the 7th percentile – i.e., 7% of its contemporaries scored the same or lower than it.