title: Cell-associated and extracellular phospholipid transfer protein in human coronary atherosclerosis.
abstract: BACKGROUND
  Phospholipid transfer protein (PLTP) plays an important role in HDL particle metabolism and may modulate hepatic secretion of apolipoprotein B-containing lipoproteins. However, whether PLTP might participate directly in human atherosclerotic lesion formation is unknown.
  
  
  RESULTS
  The cellular and extracellular distributions of PLTP were determined in normal and atherosclerotic human coronary lesions with a monoclonal antibody to human PLTP. Cell types (smooth muscle cells [SMCs] or macrophages), apolipoproteins (apoA-I, apoB, and apoE), and extracellular matrix proteoglycans (biglycan and versican) were identified on adjacent sections with monospecific antibodies. Minimal extracellular PLTP was detected in nonatherosclerotic coronary arteries, but extracellular and cellular PLTP immunostaining was widespread in atherosclerotic lesions. PLTP was detected in foam cell SMCs and in foam cell macrophages, which suggests that cellular cholesterol accumulation might increase PLTP expression in both cell types. This was confirmed by in vitro studies demonstrating that cholesterol loading of macrophages leads to 2- to 3-fold increases in PLTP steady-state mRNA levels, protein expression, and activity. PLTP also was detected in an extracellular distribution, colocalizing with apoA-I, apoB, apoE, and the vascular proteoglycan biglycan. In gel mobility shift assays, both active and inactive recombinant PLTP markedly increased HDL binding to biglycan, which suggests that PLTP may mediate lipoprotein binding to proteoglycans independent of its phospholipid transfer activity.
  
  
  CONCLUSIONS
  PLTP is present in human atherosclerotic lesions, and its distribution suggests roles for PLTP in both cellular cholesterol metabolism and lipoprotein retention on extracellular matrix.
authors.affiliation: Division of Cardiology, Department of Medicine, University of Washington, Seattle, Wash, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: O'Brien
authors.forename: Simona
authors.initials: S
authors.lastname: Vuletic
authors.forename: Thomas O
authors.initials: TO
authors.lastname: McDonald
authors.forename: Gertrud
authors.initials: G
authors.lastname: Wolfbauer
authors.forename: Katherine
authors.initials: K
authors.lastname: Lewis
authors.forename: An-Yue
authors.initials: AY
authors.lastname: Tu
authors.forename: Santica
authors.initials: S
authors.lastname: Marcovina
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
authors.forename: Alan
authors.initials: A
authors.lastname: Chait
authors.forename: John J
authors.initials: JJ
authors.lastname: Albers
mesh_terms: D000918:Antibody Specificity; D001053:Apolipoproteins / Q000032:analysis / Q000378:metabolism; D058578:Biglycan; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology*; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism*; D005487:Foam Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D049294:Phospholipid Transfer Proteins; D011509:Proteoglycans / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
chemical_list: D001053:Apolipoproteins; C546884:BGN protein, human; D058578:Biglycan; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D002784:Cholesterol