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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2000-6-16
pubmed:abstractText
BACKGROUND: Adhesive interactions between leukocytes and endothelial cells are characteristic of the development of atherosclerotic lesions, but the receptors involved remain to be defined. P-selectin is an adhesion receptor expressed on activated endothelial cells or platelets and was shown to be involved in fatty streak formation in LDL receptor-deficient mice on an atherogenic diet. The main purpose of this study is to examine the role of P-selectin in the spontaneous development of advanced atherosclerosis in apoE-deficient mice. METHODDS AND RESULTS: We intercrossed P-selectin-deficient mice with mice lacking apoE and compared lesion development in apoE-deficient mice with P-selectin (apoE(-/-) P(+/+)) and without P-selectin (apoE(-/-) P(-/-)) that were fed normal mouse chow. At 4 months of age, apoE(-/-) P(-/-) mice had 3. 5-fold smaller aortic sinus lesions than apoE(-/-) P(+/+) mice. These were limited to fatty streaks in the apoE(-/-) P(-/-) mice, whereas 70% of apoE(-/-) P(+/+) lesions contained smooth muscle cells. Significantly more of the aortic sinus circumference was covered by lesions in the apoE(-/-) P(+/+) animals. The P-selectin genotype affected macrophage recruitment, because twice as many mononuclear cells were present in the P-selectin-positive lesions. At 15 months, the lesions progressed to the fibrous plaque stage in both genotypes and spread throughout the aorta, but this process was delayed in apoE(-/-) P(-/-) mice. In the aortic sinus, the lesions of the apoE(-/-) P(-/-) mice were 2.6-fold smaller and less calcified. CONCLUSIONS: P-selectin appears to be a key adhesion receptor mediating leukocyte recruitment into lesions and promoting advanced atherosclerosis in apoE-deficient mice.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1524-4539
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2290-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Prominent role of P-selectin in the development of advanced atherosclerosis in ApoE-deficient mice.
pubmed:affiliation
Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't