Year-end Sale % OFF 
Abstract
Lipoprotein oxidation plays an important role in pathogenesis of atherosclerosis. Oxidized low density lipoprotein (OxLDL) induces profound inflammatory responses in vascular cells, such as production of monocyte chemoattractant protein-1 (MCP-1) [chemokine (C-C motif) ligand 2], a key chemokine in the initiation and progression of vascular inflammation. Here we demonstrate that OxLDL also binds MCP-1 and that the OxLDL-bound MCP-1 retains its ability to recruit monocytes. A human MCP-1 mutant in which basic amino acids Arg-18 and Lys-19 were replaced with Ala did not bind to OxLDL. The MCP-1 binding to OxLDL was inhibited by the monoclonal antibody E06, which binds oxidized phospholipids (OxPLs) in OxLDL. Because OxPLs are carried by lipoprotein(a) [Lp(a)] in human plasma, we tested to determine whether Lp(a) binds MCP-1. Recombinant wild-type but not mutant MCP-1 added to human plasma bound to Lp(a), and its binding was inhibited by E06. Lp(a) captured from human plasma contained MCP-1 and the Lp(a)-associated endogenous MCP-1 induced monocyte migration. These results demonstrate that OxLDL and Lp(a) bind MCP-1 in vitro and in vivo and that OxPLs are major determinants of the MCP-1 binding. The association of MCP-1 with OxLDL and Lp(a) may play a role in modulating monocyte trafficking during atherogenesis.
Highlights
Lipoprotein oxidation plays an important role in pathogenesis of atherosclerosis
To test the hypothesis that monocyte chemoattractant protein-1 (MCP-1) binds to Oxidized low density lipoprotein (OxLDL), MCP-1 was combined with OxLDL or Native LDL (nLDL), loaded onto a size exclusion column, and eluted fractions were analyzed for apoB-100 and MCP-1 content
MCP-1 binding to OxLDL was confirmed in a native gel electrophoresis experiment in which MCP-1 migrated with the apoB band (Fig. 3A)
Summary
Lipoprotein oxidation plays an important role in pathogenesis of atherosclerosis. Because OxPLs are carried by lipoprotein(a) [Lp(a)] in human plasma, we tested to determine whether Lp(a) binds MCP-1. Lp(a) captured from human plasma contained MCP-1 and the Lp(a)-associated endogenous MCP-1 induced monocyte migration. These results demonstrate that OxLDL and Lp(a) bind MCP-1 in vitro and in vivo and that OxPLs are major determinants of the MCP-1 binding. MCP-1 binds to oxidized LDL and is carried by lipoprotein(a) in human plasma. The resulting lipid-laden macrophage foam cells are a hallmark of atherosclerotic lesions that play a central role in atherosclerosis progression. Similar to MCP-1 binding to GAGs, MCP-1 would bind to electronegative OxLDL, which in turn would play a role in guiding monocyte recruitment.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
