| First Author | Kisucka J | Year | 2009 |
| Journal | Blood | Volume | 113 |
| Issue | 23 | Pages | 6015-22 |
| PubMed ID | 19349621 | Mgi Jnum | J:149496 |
| Mgi Id | MGI:3848602 | Doi | 10.1182/blood-2008-10-186650 |
| Citation | Kisucka J, et al. (2009) Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis. Blood 113(23):6015-22 |
| abstractText | 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(DeltaCT/DeltaCT) mice in which the endogenous P-selectin gene was replaced with a mutant that produces abnormally high plasma levels of sP-selectin. P-sel(DeltaCT/DeltaCT) 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. |
