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Cardiovascular Research 2001 49(2):456-465; doi:10.1016/S0008-6363(00)00274-1
© 2001 by European Society of Cardiology
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Copyright © 2000, European Society of Cardiology

The effects of gemfibrozil upon the metabolism of chylomicron-like emulsions in patients with endogenous hypertriglyceridemia

Raul D. Santosa,b, Laura I. Venturaa, Andrei C. Spósitoa, Roberto Schreibera, José A.F. Ramiresa and Raul C. Maranhãoa,b,*

aThe Heart Institute of the Medical School Hospital (InCor), University of São Paulo, São Paulo, Brazil
bFaculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

* Corresponding author. Laboratório de Metabolismo Lipídico, Instituto do Coração-HCFMUSP, Av. Dr. Enéas C. Aguiar, 44, 05403-000 Sao Paulo-SP, Brazil. Tel.: +55-11-3068-8794; fax: +55-11-3063-0779 ramarans{at}usp.br

Objective: To evaluate the effects of gemfibrozil upon the intravascular metabolism of chylomicron-like emulsions in endogenous hypertriglyceridemia. Methods: We evaluated the plasma kinetics of a chylomicron-like emulsion in 39 subjects: 27 hypertriglyceridemics, total cholesterol (TC) expressed as median (%25; %75) 7.47 (6.1; 8.19) mmol/l and plasma triglycerides (TG) 4.28 (3.6; 18.5) mmol/l and in 12 normolipidemics, TC 4.7 (3.85; 5.37) mmol/l and TG 0.91 (0.64; 1.75) mmol/l. Hypertriglyceridemics were evaluated at baseline and after a 30-day 1200-mg/day gemfibrozil (n = 8) or placebo treatment (n = 7). The emulsion labelled with 14C-cholesteryl oleate (14C-CO) and 3H-triolein (3H-TO) was injected intravenously after a 12-h fast. The plasma kinetics of 3H-TO and 14C-CO were determined to assess, respectively, lipolysis and clearance of chylomicron and remnants by compartmental analysis. Results: The residence times (in minutes) of 3H-TO and 14C-CO of hypertriglyceridemics were roughly twice the values of normolipidemics, i.e. 8.0 (5.5; 12.0) versus 15.0 (11.0; 24.0) and 21.5 (14.0; 33.0) versus 44.0 (32.0; 72.0), P = 0.001. Gemfibrozil treatment of hypertriglyceridemic patients reduced the residence times of 3H-TO and 14C-CO, respectively, by 46% (P = 0.003) and 53% (P = 0.008). Effects were noted on the slow phase of emulsion plasma removal, which was reduced in hypertriglyceridemics. After treatment, the emulsion residence times determined in hypertriglyceridemics attained the values of the normolipidemic group. Conclusions: Gemfibrozil treatment normalised the defects in chylomicron-like emulsion catabolism observed in endogenous hypertriglyceridemia patients.

KEYWORDS Atherosclerosis; Cholesterol; Computer modelling; Lipid metabolism; Lipoproteins


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