title: Rapid regression of atherosclerosis with MTP inhibitor treatment.
abstract: OBJECTIVE
  Regression of atherosclerosis is a vital treatment goal of atherosclerotic vascular disease. Inhibitors of the microsomal triglyceride transfer protein (MTP) have been shown to reduce apolipoprotein B (apoB)-containing lipoproteins in animals and humans effectively. Therefore, the major aim of our study is to evaluate the effect of MTP inhibition on atherosclerotic plaque regression.
  
  
  METHODS
  LDL-receptor-deficient (LDLr(-/-)) mice were fed a Western diet for 16 weeks and then harvested for baseline (n = 8), switched to chow diet (n = 8) or chow diet containing MTP inhibitor (BMS 212122; n = 8) for 2 weeks before harvesting.
  
  
  RESULTS
  Treatment with MTP inhibitor led to rapid reduction in plasma lipid levels, which were accompanied by a significant decrease in lipid content and monocyte-derived (CD68+) cells in atherosclerotic plaques compared to baseline and chow diet control groups. MTP inhibitor-treated mice had increased collagen content, a marker associated with increased stability in human plaques. Furthermore, plaques of these mice showed a significant decrease in tissue factor and pro-inflammatory M1 macrophage marker monocyte chemoattractant protein-1 (MCP-I) and an increase in anti-inflammatory M2 macrophage markers arginase-I and mannose receptor 1 compared to mice in the baseline group.
  
  
  CONCLUSIONS
  Reversal of hyperlipidemia in atherosclerotic mice by inhibition of MTP leads to rapid and beneficial changes in the composition and inflammatory state of the plaque.
authors: Department of Medicine, Division of Cardiology, New York University School of Medicine, New York, NY, USA. bernd.hewing@nyumc.org
authors: Bernd
authors: B
authors: Hewing
authors: Saj
authors: S
authors: Parathath
authors: Christina K
authors: CK
authors: Mai
authors: M Isabel
authors: MI
authors: Fiel
authors: Liang
authors: L
authors: Guo
authors: Edward A
authors: EA
authors: Fisher
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy*; D001562:Benzimidazoles / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D005449:Fluorenes / Q000627:therapeutic use*; D051379:Mice; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000473:pathology
chemical_list: C424429:9-(4-(2,5-dimethyl-4-(((4'-(trifluoromethyl)(1,1'-biphenyl)-2-yl)carbonyl)amino)-1H-benzimidazol-1-yl)butyl)-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; D001055:Apolipoproteins B; D001562:Benzimidazoles; D002352:Carrier Proteins; D005449:Fluorenes; C106092:microsomal triglyceride transfer protein