Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2003-2-17
pubmed:abstractText
Accumulation of low-density lipoprotein (LDL)-derived cholesterol by macrophages in vessel walls is a pathogenomic feature of atherosclerotic lesions. Platelets contribute to lipid uptake by macrophages through mechanisms that are only partially understood. We have previously shown that platelet factor 4 (PF4) inhibits the binding and degradation of LDL through its receptor, a process that could promote the formation of oxidized LDL (ox-LDL). We have now characterized the effect of PF4 on the binding of ox-LDL to vascular cells and macrophages and on the accumulation of cholesterol esters. PF4 bound to ox-LDL directly and also increased ox-LDL binding to vascular cells and macrophages. PF4 did not stimulate ox-LDL binding to cells that do not synthesize glycosaminoglycans or after enzymatic cleavage of cell surface heparan and chondroitin sulfates. The effect of PF4 on binding ox-LDL was dependent on specific lysine residues in its C terminus. Addition of PF4 also caused an approximately 10-fold increase in the amount of ox-LDL esterified by macrophages. Furthermore, PF4 and ox-LDL co-localize in atherosclerotic lesion, especially in macrophage-derived foam cells. These observations offer a potential mechanism by which platelet activation at sites of vascular injury may promote the accumulation of deleterious lipoproteins and offer a new focus for pharmacological intervention in the development of atherosclerosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6187-93
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12466273-Amino Acid Substitution, pubmed-meshheading:12466273-Animals, pubmed-meshheading:12466273-Arteriosclerosis, pubmed-meshheading:12466273-Blood Platelets, pubmed-meshheading:12466273-CHO Cells, pubmed-meshheading:12466273-Cells, Cultured, pubmed-meshheading:12466273-Cricetinae, pubmed-meshheading:12466273-Endothelium, Vascular, pubmed-meshheading:12466273-Genetic Variation, pubmed-meshheading:12466273-Humans, pubmed-meshheading:12466273-Immunohistochemistry, pubmed-meshheading:12466273-Lipoproteins, LDL, pubmed-meshheading:12466273-Microscopy, Confocal, pubmed-meshheading:12466273-Mutagenesis, Site-Directed, pubmed-meshheading:12466273-Platelet Factor 4, pubmed-meshheading:12466273-Protein Binding, pubmed-meshheading:12466273-Proteoglycans, pubmed-meshheading:12466273-Recombinant Proteins, pubmed-meshheading:12466273-Transfection, pubmed-meshheading:12466273-Umbilical Veins
pubmed:year
2003
pubmed:articleTitle
Platelet factor 4 enhances the binding of oxidized low-density lipoprotein to vascular wall cells.
pubmed:affiliation
Department of Clinical Biochemistry, the Center for Research, Prevention, and Treatment of Atherosclerosis, Hadassah University Hospital and Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
pubmed:publicationType
Journal Article