Probucol promotes reverse cholesterol transport in heterozygous familial hypercholesterolemia. Effects on apolipoprotein AI-containing lipoprotein particles.
In order to investigate the effect of Probucol therapy on reverse cholesterol transport, apo AI-containing lipoprotein particles were isolated and characterized, and their cholesterol effluxing capacity and LCAT activity were assayed in four familial hypercholesterolemia patients before and after 12 weeks of Probucol therapy. Four major subpopulations of apo A-containing lipoprotein particles are separated before and after drug treatment; LpAI, LpAI:AII, LpAIV, LpAI:AIV:AII. Probucol reduces both total plasma and LDL-cholesterol (-17 and -14%, respectively). Apo B decreases slightly (-7.6%). Plasma HDL-cholesterol and apo AI decrease by 36.6 and 34.7%. LpA-I showed a marked decrease (-46%). Moreover, plasma LCAT and CETP activities were markedly increased under Probucol treatment. Analysis of lipoprotein particles showed that Probucol induces a decrease of protein content and an increase of cholesterol and triglycerides contents. Interestingly, Probucol induces an enhancement of LCAT activity in LpAI (4.5-fold). This drug induces a trend toward greater cholesterol efflux from cholesterol-preloaded adipose cells promoted by Lp AI and Lp AIV but not by Lp AI:AII. This study confirms the hypothesis, in addition to the lowering LDL-cholesterol levels and antioxidant effects of Probucol, that HDL reduction was not an atherogenic change in HDL system but may cause an antiatherogenic action by accelerating cholesterol transport through HDL system, promoting reverse cholesterol transport from peripheral tissues.
Adlouni
A
A
Laboratoire de Recherche sur les Lipoprotéines, Faculté des Sciences Ben Msik, Sidi Othman, 7955, Casablanca, Morocco. aadlouni@hotmail.com
El Messal
M
M
Saïle
R
R
Parra
H
H
Fruchart
J
J
Ghalim
N
N
D017667:Adipocytes / Q000378:metabolism; D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D016632:Apolipoprotein A-I / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000097:blood; D002784:Cholesterol / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D017270:Lipoprotein(a) / Q000031:analogs & derivatives* / Q000378:metabolism; D008875:Middle Aged; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D011341:Probucol / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D017270:Lipoprotein(a); C078260:lipoprotein A-I; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D011341:Probucol