title: Macrophage cholesterol efflux to plasma and HDL in subjects with low and high homocysteine levels: a FIELD substudy.
abstract: OBJECTIVE
  Increases of homocysteine (Hcy) by fenofibrate correlated inversely to changes in HDL-C and apoA-I in the FIELD study. This finding raised the question whether high Hcy may influence HDL function and counteract benefits of fenofibrate on cardiovascular outcomes. In a subset of the FIELD study we investigated whether fenofibrate therapy or high Hcy, separately or in concert, modulate: (1) ability of plasma or HDL to facilitate cholesterol efflux from THP-1 foam cells; (2) plasma potential to generate preβ-HDL; (3) plasma phospholipid transfer protein (PLTP) activity, serum PON-1 mass and activity, HDL particle size and distribution.
  
  
  METHODS
  We selected 33 subjects in the FIELD fenofibrate arm according to quartiles of Hcy at 5th year: 17 subjects were in the lowest (Low Hcy group) and 16 subjects were in the highest quartile (High Hcy group). In addition, 14 subjects allocated to placebo were matched by close-out Hcy levels to Low Hcy group. This design allowed us to examine the effects of both fenofibrate (comparison between placebo vs Low Hcy groups) and Hcy (comparison between close-out Low and High Hcy groups) on plasma and HDL ability to facilitate cellular cholesterol removal in the efflux assay in vitro using THP-1 foam cells.
  
  
  RESULTS
  Hcy levels were 13.3±0.7 μmol/L (placebo), 13.2±2 μmol/L (Low Hcy) and 27.4±6.5 μmol/L (High Hcy). Cholesterol efflux values to HDL and plasma, percentage of plasma preβ-HDL, PLTP activity, serum PON-1 mass and HDL particle size and distribution were similar in both fenofibrate groups and comparable to those of the placebo group.
  
  
  CONCLUSIONS
  In the present study cohort fenofibrate and high Hcy levels did not modulate HDL and plasma functions in the first step of reverse cholesterol transport, cholesterol efflux from foam cells.
authors.affiliation: Helsinki University Central Hospital, Biomedicum, Haartmaninkatu 8 PO Box 700, FIN-00029 Helsinki, Finland. marianna.maranghi@uniroma1.it
authors.forename: Marianna
authors.initials: M
authors.lastname: Maranghi
authors.forename: Anne
authors.initials: A
authors.lastname: Hiukka
authors.forename: Robert
authors.initials: R
authors.lastname: Badeau
authors.forename: Jouko
authors.initials: J
authors.lastname: Sundvall
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
mesh_terms: D000368:Aged; D043303:Aryldialkylphosphatase / Q000097:blood; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D005487:Foam Cells / Q000378:metabolism*; D053442:High-Density Lipoproteins, Pre-beta / Q000378:metabolism; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D049294:Phospholipid Transfer Proteins / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D053442:High-Density Lipoproteins, Pre-beta; D049294:Phospholipid Transfer Proteins; D006710:Homocysteine; D002784:Cholesterol; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D011345:Fenofibrate