title: Acute elevation of plasma PLTP activity strongly increases pre-existing atherosclerosis.
abstract: OBJECTIVE
  A transgenic mouse model was generated that allows conditional expression of human PLTP, based on the tetracycline-responsive gene system, to study the effects of an acute increase in plasma PLTP activity as may occur in inflammation.
  
  
  RESULTS
  The effects of an acute elevation of plasma PLTP activity on the metabolism of apolipoprotein B-containing lipoproteins and on diet-induced pre-existing atherosclerosis were determined in mice displaying a humanized lipoprotein profile (low-density lipoprotein receptor knockout background). Induced expression of PLTP strongly increases plasma VLDL levels in LDL receptor knockout mice, whereas VLDL secretion is not affected. The elevation in plasma triglyceride levels is explained by a PLTP-dependent inhibition of VLDL catabolism, which is caused, at least partly, by a decreased lipoprotein lipase activity. Together with the decreased plasma HDL levels, the acutely increased PLTP expression results in a highly atherogenic lipoprotein profile. Induction of PLTP expression leads to a further increase in size of pre-existing atherosclerotic lesions, even on a chow diet. In addition, the lesions contain more macrophages and less collagen relative to controls, suggesting a less stable lesion phenotype.
  
  
  CONCLUSIONS
  In conclusion, acute elevation of PLTP activity destabilizes atherosclerotic lesions and aggravates pre-existing atherosclerosis.
authors.affiliation: Department Cell Biology & Genetics/Vascular Surgery, Erasmus University Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Moerland
authors.forename: Hannelore
authors.initials: H
authors.lastname: Samyn
authors.forename: Teus
authors.initials: T
authors.lastname: van Gent
authors.forename: Rien
authors.initials: R
authors.lastname: van Haperen
authors.forename: Geesje
authors.initials: G
authors.lastname: Dallinga-Thie
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.forename: Arie
authors.initials: A
authors.lastname: van Tol
authors.forename: Rini
authors.initials: R
authors.lastname: de Crom
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000097:blood; D050197:Atherosclerosis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000097:blood; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008049:Lipase / Q000097:blood; D008071:Lipoprotein Lipase / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D049294:Phospholipid Transfer Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation
chemical_list: D001055:Apolipoproteins B; D002791:Cholesterol, Dietary; D008079:Lipoproteins, VLDL; C493430:PLTP protein, human; D049294:Phospholipid Transfer Proteins; D011973:Receptors, LDL; D014280:Triglycerides; D003094:Collagen; D008049:Lipase; C495700:Lipc protein, mouse; D008071:Lipoprotein Lipase