title: Enhanced atherothrombotic formation after oxidative injury by FeCl3 to the common carotid artery in severe combined hyperlipidemic mice.
abstract: Enhanced susceptibility to atherosclerosis from severe hypertriglyceridemia (HTG) resulting from lipoprotein lipase (LPL) deficiency has been demonstrated in our recent findings which employed a unique mouse model. In the present study we provide further evidence that severe HTG due to LPL deficiency also promotes an atherothrombotic response to arterial injury induced by ferric chloride in a severe combined hyperlipidemic mouse model.
  
  
  RESULTS
  A mouse model (LPL(-/-)XApoE(-/-) double knockout, DKO) with severe combined hyperlipidemia was established by crossing ApoE and LPL-deficient mice. The common carotid arteries of ApoE knockout (EKO) and DKO mice were subjected to injury by ferric chloride, and the formation of arterial thrombosis together with various markers were compared in these lesions. DKO mice demonstrated significantly enhanced thrombus formation overlying atherosclerotic plaque after injury, which contained smooth muscle cells, macrophages, and neutral lipid. The area of neointima, mean intima/media ratios, and the percentage of luminal stenosis were significantly greater (P<0.01) in DKO mice. Compared with EKO mice, the expression of von Willebrand factor (vWF) and plasminogen activator inhibitor type 1 (PAI-1) were increased in DKO mice.
  
  
  CONCLUSIONS
  Severe combined hyperlipidemia promotes thrombosis after ferric chloride injury to atherosclerotic vessels and HTG plays a major role in the process.
authors.affiliation: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Xunde
authors.initials: X
authors.lastname: Xian
authors.forename: Yu
authors.initials: Y
authors.lastname: Ding
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Yanan
authors.initials: Y
authors.lastname: Wang
authors.forename: Michael A
authors.initials: MA
authors.lastname: McNutt
authors.forename: Colin
authors.initials: C
authors.lastname: Ross
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.forename: Xuming
authors.initials: X
authors.lastname: Deng
authors.forename: George
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology*; D017536:Carotid Artery, Common / Q000187:drug effects / Q000473:pathology*; D002712:Chlorides / Q000633:toxicity; D004195:Disease Models, Animal; D005290:Ferric Compounds / Q000633:toxicity; D015228:Hypertriglyceridemia / Q000150:complications* / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D013927:Thrombosis / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology*; D014841:von Willebrand Factor / Q000096:biosynthesis
chemical_list: D001057:Apolipoproteins E; D002712:Chlorides; D005290:Ferric Compounds; D017395:Plasminogen Activator Inhibitor 1; D014841:von Willebrand Factor; D008071:Lipoprotein Lipase