title: Reverse apolipoprotein A-I mimetic peptide R-D4F inhibits neointimal formation following carotid artery ligation in mice.
abstract: The ApoA-I mimetic peptide D-4F has demonstrated potent atheroprotective actions in vivo and in vitro. We investigated the effect of R-D4F (ie, the D-4F peptide with reverse order of amino acids) on intimal hyperplasia after vascular injury in a mouse model of carotid artery ligation. Adult male C57BL/6J mice were pretreated intraperitoneally with vehicle, D-4F (1 mg/kg), or R-D4F (1 mg/kg or 5 mg/kg) daily for 3 days; the mice were then subjected to left carotid artery ligation. All treatments were continued for 28 days after surgery. Neither D-4F nor R-D4F treatment affected serum lipid levels. Morphometric analysis showed that the occluded vessels had significant neointimal formation, compared with the uninjured arteries in vehicle-treated mice. Like the D-4F treatment, R-D4F treatment significantly (P < 0.05) inhibited intimal hyperplasia (-42%), local neutrophil and macrophage infiltration, and mRNA expression of the proinflammatory mediator monocyte chemotactic protein 1 (-55%) and vascular cell adhesion protein 1 (-53%), compared with vehicle. Furthermore, the vasoprotective effect of high-dose R-D4F was significantly enhanced, compared with the low dose. In cultured mouse RAW 264.7 macrophages, pretreatment with R-D4F also effectively inhibited lipopolysaccharide-induced leukocyte integrin CD11b expression, a key molecule for leukocyte infiltration. Taken together, these results suggest that R-D4F has significant anti-inflammatory features and facilitates prevention of neointimal formation after vascular injury in mice.
authors.affiliation: Department of Cardiology, Second Clinic Medical College, Yangzhou University, Yangzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Du
authors.forename: Xinkai
authors.initials: X
authors.lastname: Qu
authors.forename: Haixia
authors.initials: H
authors.lastname: Zheng
authors.forename: Rujun
authors.initials: R
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Mingxing
authors.initials: M
authors.lastname: Chen
authors.forename: Pei
authors.initials: P
authors.lastname: Zhao
authors.forename: Zhengang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Kaizheng
authors.initials: K
authors.lastname: Gong
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D039481:CD11b Antigen / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology*; D016893:Carotid Stenosis / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D002460:Cell Line; D007249:Inflammation / Q000097:blood / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008026:Ligation; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058426:Neointima / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D018836:Inflammation Mediators; D008055:Lipids; D008070:Lipopolysaccharides; D010455:Peptides; D012333:RNA, Messenger; C582295:apolipoprotein A-I mimetic peptide 4F