Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor

In view of the evidence linking plasma high density lipopro-tein (HDL)-cholesterol levels to a protective effect against coronary artery disease and the widespread use of fibrates in the treatment of hyperlipidemia, the goal of this study was to analyze the influence of fibrates on the expression of apolipoprotein (apo) A-Il, a major protein constituent of HDL. Administration of fenofibrate (300 mg/d) to 16 pa-tients with coronary artery disease resulted in a marked increase in plasma apo A-Il concentrations (0.34±0.11 to 0.45+0.17 grams/liter; P < 0.01). This increase in plasma apo A-Il was due to a direct effect on hepatic apo A-Il production, since fenofibric acid induced apo A-Il mRNA levels to 450 and 250 % of control levels in primary cultures ofhuman hepatocytes and in human hepatoblastoma HepG