Platelet factor 4 enhances the binding of oxidized low-density lipoprotein to vascular wall cells

Taher Nassar, Bruce S. Sachais, Sa'ed Akkawi, Maria Anna Kowalska, Khalil Bdeir, Eran Leitersdorf, Edna Hiss, Leah Ziporen, Michael Aviram, Douglas Cines, Mortimer Poncz*, Abd Al Roof Higazi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

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 ∼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.

Original languageAmerican English
Pages (from-to)6187-6193
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number8
DOIs
StatePublished - 21 Feb 2003
Externally publishedYes

Fingerprint

Dive into the research topics of 'Platelet factor 4 enhances the binding of oxidized low-density lipoprotein to vascular wall cells'. Together they form a unique fingerprint.

Cite this