title: Design and validation of a specific scavenger receptor class AI binding peptide for targeting the inflammatory atherosclerotic plaque.
abstract: OBJECTIVE
  Scavenger receptor A (SR-A) is abundantly expressed by macrophage and plays a critical role in foam cell formation and atherogenesis. In search of selective SR-AI antagonists, we have used affinity selection of a phage displayed peptide library on the synthetic extracellular domain of SR-AI.
  
  
  RESULTS
  Phage selection led to an almost 1,000-fold enrichment of SR-AI binding phage, which bound avidly to human THP-1 cells. A 15-mer corresponding to the peptide insert of the major SR-AI binding phage (PP1) displaced phage binding to SR-AI. Peptides, docked to a streptavidin scaffold, were effectively internalized by macrophages in an SR-AI-dependent manner. The enriched phage pool and streptavidin bound PP1 exhibited marked uptake by hepatic macrophages in mice. Importantly, PP1 significantly increased streptavidin as well as particulate accumulation in advanced aortic plaques, and in particular intraplaque macrophage, of apolipoprotein E(-/-) mice.
  
  
  CONCLUSIONS
  We have identified a novel peptide antagonist selective for SR-AI; this antagonist could be a valuable tool in SR-AI targeted imaging of atherosclerotic lesions.
authors.affiliation: Department of General Surgery, Maastricht University, the Netherlands. f.segers@maastrichtuniversity.nl
authors.forename: Filip M E
authors.initials: FM
authors.lastname: Segers
authors.forename: Haixiang
authors.initials: H
authors.lastname: Yu
authors.forename: Tom J M
authors.initials: TJ
authors.lastname: Molenaar
authors.forename: Perry
authors.initials: P
authors.lastname: Prince
authors.forename: Toshiki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Theo J C
authors.initials: TJ
authors.lastname: van Berkel
authors.forename: Erik A L
authors.initials: EA
authors.lastname: Biessen
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001345:Autoradiography; D001667:Binding, Competitive; D019556:COS Cells; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D051117:Scavenger Receptors, Class A / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019809:Streptavidin / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D004337:Drug Carriers; D008024:Ligands; C495139:MSR1 protein, human; C495140:Msr1 protein, mouse; D019151:Peptide Library; D010455:Peptides; D051117:Scavenger Receptors, Class A; D019809:Streptavidin