title: Alprostadil liposome microsphere preparation stabilizes vascular plaques and inhibits intra-plaque inflammation.
abstract: BACKGROUND
  Vulnerable plaques play an important role in the onset of sudden cardiac events and strokes. How to stabilize vulnerable plaques is still a challenge to medical science. Alprostadil is a biologically active substance with strong activity on vessel. Our study assessed the stabilizing effects of an alprostadil liposome microsphere preparation (ALMP) on vulnerable plaques in the brachiocephalic artery of apolipoprotein E (Apo E) knockout mice.
  
  
  METHODS
  Seventy-two male Apo E-knockout mice were fed a high-fat diet beginning at eight weeks of age. At week 17, they were divided randomly into groups for treatment with a high dose (3.6 µg×kg(-1)×d(-1)) or low dose (1.8 µg×kg(-1)×d(-1)) of an ALMP, or 0.2 ml/d normal saline (control group). The drug was administered using a micro-capsule pump. Twenty weeks after drug administration, pathological changes in the vulnerable plaques within the brachiocephalic artery were assessed, and levels of anti-mouse monocyte/macrophage monoclonal antibody (MOMA-2) and superoxide anions in the plaques were detected using immunofluorescence. The soluble intercellular adhesion molecule-1 (ICAM-1) expression was measured by ELISA, and the expression of matrix metalloproteinase-9 (MMP-9) and CD40 mRNA was measured using RT-PCR. Thrombospindin-1 (TSP-1) expression was detected using Western blotting.
  
  
  RESULTS
  Compared with the control group, ALMP treatment significantly reduced the plaque area in the brachiocephalic artery (P < 0.01), significantly lowered the contents of the lipid core (P < 0.01), significantly reduced the number of ruptured fibrous caps (P < 0.05), and increased the thickness of the fibrous cap and significantly reduced the incidence of intra-plaque hemorrhage (P < 0.05). ALMP treatment significantly reduced the expression of MOMA-2, superoxide anion, MMP-9, ICAM-1 and CD40 in the plaques (P < 0.01), decreased plasma ICAM-1 expression (P < 0.01), and increased the expression of TSP-1.
  
  
  CONCLUSIONS
  Treatment with ALMP can stabilize vulnerable plaques by inhibiting inflammation.
authors.affiliation: Department of National Integrative Medicine, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Wen-li
authors.initials: WL
authors.lastname: Cheng
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuan-nan
authors.initials: YN
authors.lastname: Ke
authors.forename: Shu-ying
authors.initials: SY
authors.lastname: Fan
authors.forename: Lin
authors.initials: L
authors.lastname: Pan
authors.forename: Yan-ru
authors.initials: YR
authors.lastname: Guo
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
mesh_terms: D000527:Alprostadil / Q000737:chemistry* / Q000627:therapeutic use*; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008863:Microspheres; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction
chemical_list: D008081:Liposomes; D018799:Intercellular Adhesion Molecule-1; D000527:Alprostadil