Apolipoprotein AI and AII metabolism in patients with primary high-density lipoprotein deficiency associated with familial hypertriglyceridemia.
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 five normolipidemic controls. Autologous 125I labeled HDL were injected intravenously (IV; 25 microCi) and blood samples drawn ten minutes after the injection and periodically thereafter for 12 days. Urine samples were collected daily and their radioactivity measured. Kinetic parameters were calculated from the area under the decay curve using three exponentials. 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 mean 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). In vitro lipolysis of triglyceride (TG) rich lipoproteins by bovine lipoprotein lipase, and measurement of hepatic TG lipase and lipoprotein lipase in postheparin plasma were similar in patients and controls, indicating no abnormality in these factors that are linked to HDL and TG catabolism. However, a significant positive correlation between hepatic TG lipase and the FCR of apo AI and apo AII was found. The data suggest that in this series of patients with HDL deficiency the low plasma HDL-cholesterol, apo AI, and apo AII levels resulted from decreased synthesis and an increased fractional catabolic rate of apo AI and apo AII, the major proteins of HDL.
D000328:Adult; D000818:Animals; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001054:Apolipoproteins A / Q000097:blood / Q000378:metabolism*; D002417:Cattle; D002784:Cholesterol / Q000097:blood; D006493:Heparin; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000097:blood / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008049:Lipase / Q000097:blood; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000097:blood / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000172:deficiency* / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001054:Apolipoproteins A; D008075:Lipoproteins, HDL; D014280:Triglycerides; D006493:Heparin; D002784:Cholesterol; D008049:Lipase; D008071:Lipoprotein Lipase