Probucol treatment results in a significant reduction of plasma high-density lipoprotein (HDL) levels. Since the remodeling of HDL within the plasma compartment is a crucial determinant of HDL levels, the activities of several factors participating in the process, ie, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and lipoprotein and hepatic lipases (LPL, HL), were evaluated in 15 hypercholesterolemic patients treated with probucol (1 g/d) for 8 weeks. Drug treatment was associated with significant reductions of HDL cholesterol ([HDL-C] -32%), HDL2-C (-65%), HDL3-C (-22%), apolipoprotein (apo) A-I (-27%), and apo A-II (-11%) levels and with the accumulation of small HDL in plasma. CETP activity increased by 48%, with minor changes in LCAT (-7%), LPL (+4%), and HL (-7%) activities. By linear regression analysis, CETP activity correlated inversely with HDL-C, HDL2-C, and apo A-I levels (r = -.63, -.52, and -.73, respectively) and with HDL particle size. In multivariate analysis, CETP activity was the strongest predictor of HDL-C levels, apo A-I levels, and HDL particle size. The hypothetical mechanism of probucol is a stimulation of CETP activity, resulting in the formation of triglyceride (TG)-enriched HDL. These are acted on by HL, leading to the accumulation of small HDL in plasma.
Mechanisms of high-density lipoprotein reduction after probucol treatment: Changes in plasma cholesterol esterification/transfer and lipase-activities / G. Chiesa, S. Michelagnoli, M. Cassinotti, G. Gianfranceschi, J. Werba, F. Pazzucconi, C.R. Sirtori, G. Franceschini. - In: METABOLISM, CLINICAL AND EXPERIMENTAL. - ISSN 0026-0495. - 42:2(1993), pp. 229-235.
|Titolo:||Mechanisms of high-density lipoprotein reduction after probucol treatment: Changes in plasma cholesterol esterification/transfer and lipase-activities|
CHIESA, GIULIA MARIA CAROLA (Primo)
SIRTORI, CESARE (Penultimo)
FRANCESCHINI, GUIDO (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||1993|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/0026-0495(93)90041-L|
|Appare nelle tipologie:||01 - Articolo su periodico|