Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis

Janka Kisucka; Anil K Chauhan; Bing-Qiao Zhao; Ian S Patten; Ayce Yesilaltay; Monty Krieger; Denisa D Wagner

doi:10.1182/blood-2008-10-186650

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Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis

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Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis

Janka Kisucka, Anil K Chauhan, Bing-Qiao Zhao, Ian S Patten, Ayce Yesilaltay, Monty Krieger and Denisa D Wagner

Blood, Vol.113(23), pp.6015-6022

Vascular Biology

06/04/2009

DOI: 10.1182/blood-2008-10-186650

PMCID: PMC2700332

PMID: 19349621

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Abstract

Cerebrovascular and cardiovascular diseases are a major cause of morbidity and mortality. Soluble P-selectin (sP-selectin) is a biomarker for platelet/endothelial activation and is considered a risk factor for vascular disease. sP-selectin enhances procoagulant activity by inducing leukocyte-derived microparticle production and promotes activation of leukocyte integrins. However, it is not known whether it directly contributes to vascular complications. We investigated the effect of increased levels of sP-selectin on blood-brain barrier (BBB) function, stroke outcome, and atherosclerosis by comparing wild-type mice with P-sel Δ CT /Δ CT mice in which the endogenous P-selectin gene was replaced with a mutant that produces abnormally high plasma levels of sP-selectin. P-sel Δ CT /Δ CT mice presented several abnormalities, including (1) higher BBB permeability, with 25% of the animals showing differential permeability between the right and left hemispheres; (2) altered social behavior with increased aggression; (3) larger infarcts in the middle cerebral artery occlusion ischemic stroke model; and (4) increased susceptibility to atherosclerotic, macrophage-rich lesion development in both male and female mice on the apoE −/− genetic background. Thus, elevated sP-selectin is not only a biomarker for vascular disease, but also may contribute directly to atherosclerosis and cerebrovascular complications.

Vascular Biology

Details

Title: Subtitle: Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis
Creators: Janka Kisucka - Immune Disease Institute and
Anil K Chauhan - Immune Disease Institute and
Bing-Qiao Zhao - Immune Disease Institute and
Ian S Patten - Immune Disease Institute and
Ayce Yesilaltay - Department of Biology, Massachusetts Institute of Technology, Cambridge
Monty Krieger - Department of Biology, Massachusetts Institute of Technology, Cambridge
Denisa D Wagner - Immune Disease Institute and
Resource Type: Journal article
Publication Details: Blood, Vol.113(23), pp.6015-6022
Publisher: American Society of Hematology
Series: Vascular Biology
DOI: 10.1182/blood-2008-10-186650
PMID: 19349621
PMCID: PMC2700332
ISSN: 0006-4971
eISSN: 1528-0020
Grant note: HL056949; HL066105 / National Institutes of Health
Language: English
Date published: 06/04/2009
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094738002771

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