title: Mast cell degranulator compound 48-80 promotes atherosclerotic plaque in apolipoprotein E knockout mice with perivascular common carotid collar placement.
abstract: BACKGROUND
  Study of the relationship between mast cells and atherosclerosis is mostly dependent on pathological observation and cytology experiments. To investigate the effects of mast cells degranulation on plaque and their possible mechanisms we used apolipoprotein E knockout mice which had been placed perivascular common carotid collar with mast cells degranulator compound 48-80.
  
  
  METHODS
  Forty apolipoprotein E knockout mice were fed a western-type diet and operated on with placement of perivascular right common carotid collar. Four weeks after surgery, the mice were intraperitoneally injected with compound 48-80 (0.5 mg/kg) or D-Hanks every other day for 4 times. The serum lipids and activity of tryptase were measured. Tissue sections were stained with hematoxylin and eosin. Corresponding sections were stained with toluidine blue and immunohistochemically with antibodies against macrophage-specific antigen, alpha-smooth muscle actin, interleukin-1beta and von Willebrand factor. Simultaneously, basic fibroblast growth factor was detected by in situ hybridization and immunofluorescence.
  
  
  RESULTS
  No pathological change was observed in common carotid non-collar placement but atherogenesis in common carotid collar placement of both groups. There was a significant increase in plaque area ((5.85+/-0.75) x 10(4) vs (0.86+/-0.28) x 10(4) microm(2), P<0.05), the degree of lumen stenosis ((81+/-15)% vs (41+/-12)%, P<0.05), the activity of tryptase in serum ((0.57+/-0.13) U/L vs (0.36+/-0.10) U/L, P<0.05), and the percentage of degranulated mast cells ((80.6+/-17.8)% vs (13.5+/-4.1)%, P<0.05). The expressions of macrophage-specific antigen, alpha-smooth muscle actin, interleukin-1beta, basic fibroblast growth factor and the density of neovessel in plaque were more in the compound 48-80 group than in the control group.
  
  
  CONCLUSIONS
  Perivascular common carotid collar placement can promote atherosclerotic plaque formation in apolipoprotein E knockout mice. Compound 48-80 increases plaque area and the degree of lumen stenosis by the mechanism that compound 48-80 promotes proliferation of smooth muscle cells and aggregation of macrophages. Compound 48-80 promotes angiogenesis in plaque. The mechanism is potentially that compound 48-80 increases the expressions of basic fibroblast growth factor mRNA and protein in plaque. Compound 48-80 enhances the expression of interleukin-1beta in plaque.
authors.affiliation: Institute of Cardiovascular Diseases, Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Ya-ling
authors.initials: YL
authors.lastname: Tang
authors.forename: Yong-zong
authors.initials: YZ
authors.lastname: Yang
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.forename: Chao-ke
authors.initials: CK
authors.lastname: Tang
authors.forename: Zeng-xiang
authors.initials: ZX
authors.lastname: Xu
authors.forename: Yu-hui
authors.initials: YH
authors.lastname: Sun
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
chemical_list: D001057:Apolipoproteins E; D003189:p-Methoxy-N-methylphenethylamine