title: Development of Novel Diagnostic Agents for Atherosclerosis Using Fluorescence-labeled Peptides.
abstract: The oxidative modification of low-density lipoprotein (LDL) is believed to play an important role in the pathogenesis of atherosclerosis. Therefore, probes for detection of oxidized LDL (ox-LDL) in atherosclerotic plaques and plasma are expected to be useful for the diagnosis of atherosclerosis. Recently, we found that four fluorescein isothiocyanate (FITC)-labeled heptapeptides (Lys-Trp-Tyr-Lys-Asp-Gly-Asp, KP6)-(FITC)KP6 and (FITC-AC)KP6- and then substitution with D-Lys at the N-terminus-(FITC)dKP6 and (FITC-AC)dKP6- bind with high specificity and high affinity to two oxidized forms of LDL, heavily oxidized LDL and minimally modified LDL (MM-LDL), through binding to lysophosphatidylcholine and oxidized phosphatidylcholine, present abundantly in heavily oxidized LDL and MM-LDL. Moreover, (FITC)dKP6 and (FITC-AC)dKP6 were more stable than (FITC)KP6 and (FITC-AC)KP6 in plasma in vitro. (FITC)KP6 could detect foam cells in atherosclerotic aortic plaques of apoE-knockout mice. These results suggest that four fluorescence-labeled heptapeptides could be efficient fluorescent probes for the specific detection of ox-LDL, and can therefore contribute to the identification, diagnosis, prevention, and treatment of atherosclerosis.
authors.affiliation: Faculty of Pharmacy, Iwaki Meisei University.
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D055808:Drug Discovery; D019793:Fluorescein; D005456:Fluorescent Dyes; D005487:Foam Cells; D006801:Humans; D017879:Isothiocyanates; D008077:Lipoproteins, LDL / Q000032:analysis / Q000097:blood*; D051379:Mice; D010455:Peptides; D058226:Plaque, Atherosclerotic / Q000737:chemistry
chemical_list: D015415:Biomarkers; D005456:Fluorescent Dyes; D017879:Isothiocyanates; D008077:Lipoproteins, LDL; D010455:Peptides; C099252:oxidized low density lipoprotein; D019793:Fluorescein