Plasma
high density lipoproteins (HDL) and their major
proteins--
apolipoprotein (
apo) AI and
apo AII--are subnormal in most patients with
familial hypertriglyceridemia. However, the pathophysiology of low plasma
apo AI and
apo AII is unclear. The kinetic parameters (turnover) of HDL
apo AI and
apo AII were studied in six lean patients with primary HDL deficiency associated with
familial hypertriglyceridemia and normolipidemic healthy controls. The radioactivity decay curve of 125I labelled HDL was used for assessment of kinetics. Mean plasma
apo AI and
apo AII were significantly lower (p less than 0.001) in patients than normals (70.4 +/- 2.7 v 106.9 +/- 7.0; 24.2 +/- 1.6 v 39.2 +/- 0.9 mg/dl, respectively). The mean fractional catabolic rates (FCR) obtained from plasma 125I-HDL,
apo AI,
apo AII radioactivity decay curves and by Berson and Yalow's method (urine/plasma radioactivity ratios) were significantly greater (p less than 0.05) in patients than in controls (0.387 v 0.299; 0.391 v 0.309; 0.361 v 0.275; 0.272 v 0.207/d; respectively). The synthetic rates (SR of
apo AI and
apo AII were significantly lower in patients than in controls (11.12 v 14.17 mg/kg
body weight/d. p less than 0.05; 3.53 v 4.68 mg/kg
body weight/d, p less than 0.05, respectively). Each patient was also investigated for HDL and
triglyceride metabolism immediately before and after 8 wk of
gemfibrozil (1200 mg/d) treatment.
Gemfibrozil significantly increased plasma
HDL cholesterol,
apolipoprotein (
apo) AI, and
apo AII by 36%, 29%, and 38% from baseline, respectively. Plasma TG decreased by 54%.
Gemfibrozil increased synthetic rates of
apo AI and
apo AII by 27% and 34%, respectively, without changing the FCR.(ABSTRACT TRUNCATED AT 250 WORDS)