Effect of Pravastatin on plasma removal of a chylomicron-like emulsion in men with coronary artery disease

Santos, Raul D.; Sposito, Andrei C.; Ventura, Liliane; Cesar, Luiz Antônio Machado; Ramires, José Antônio Franchini; Maranhão, Raul C.

doi:10.1016/s0002-9149(00)00721-9

Cited by 43 publications

(46 citation statements)

References 20 publications

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“…Differences in the characteristics of the subjects, study design, methodology, and kinetic model used most likely account for the differences in results among the studies. Therefore, our results and most previous reports (55)(56)(57)(58) suggest that the reduction in intestinal lipoproteins following treatment with statins may be attributable, at least in part, to an increased uptake of these lipoproteins by LDL receptors.…”

Section: Discussionsupporting

confidence: 80%

Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia

Tremblay

Lamarche

Hogue

et al. 2009

Journal of Lipid Research

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Sixteen hyperlipidemic men were enrolled in a randomized, placebo-controlled, double-blind, cross-over study to evaluate the effect of ezetimibe 10 mg and simvastatin 40 mg, coadministered and alone, on the in vivo kinetics of apolipoprotein (apo) B-48 and B-100 in humans. Subjects underwent a primed-constant infusion of a stable isotope in the fed state. The coadministration of simvastatin and ezetimibe significantly reduced plasma concentrations of cholesterol (243.0%), LDL-C (253.6%), and triglycerides (244.0%). Triglyceride-rich lipoproteins (TRL) apoB-48 pool size (PS) was significantly decreased (248.9%) following combination therapy mainly through a significant reduction in TRL apoB-48 production rate (PR) (238.0%). The fractional catabolic rate (FCR) of VLDL and LDL apoB-100 were significantly increased with all treatment modalities compared with placebo, leading to a significant reduction in the PS of these fractions. We also observed a positive correlation between changes in TRL apoB-48 PS and changes in TRL apoB-48 PR (r 5 0.85; P , 0.0001) with combination therapy. Our results indicate that treatment with simvastatin plus ezetimibe is effective in reducing plasma TRL apoB-48 levels and that this effect is most likely mediated by a reduction in the intestinal secretion of TRL apoB-48. Our study also indicated that the reduction in LDL-C concentration following combination therapy is mainly driven by an increase in FCR of apoB-100 containing lipoproteins.-Tremblay, A. J., B. Lamarche, J-C. Hogue, and P. Couture. Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia. J. Lipid Res.

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Section: Discussionsupporting

confidence: 80%

Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia

Tremblay

Lamarche

Hogue

et al. 2009

Journal of Lipid Research

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“…In contrast, the same emulsion preparation can be used in an undetermined number of subjects. Furthermore, emulsions are easy to prepare and label with radioactive, fluorescent, or other markers, and bear the advantage of being standard uniform preparations (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). In contrast, native lipoproteins comprise different subclasses that vary widely among subjects, each one with distinct biological and pathophysiological properties.…”

mentioning

confidence: 99%

“…All these operational advantages greatly facilitate the execution of systematic studies on the plasma kinetics of lipids. Emulsion models of lymph chylomicrons have been used to clarify the chylomicron metabolism status in several disease states and the action of antilipidemic drugs upon this metabolism (6)(7)(8)(9)(10).…”

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confidence: 99%

Plasma kinetics of a cholesterol-rich emulsion in subjects with or without coronary artery disease

Santos

Hueb

Oliveira

et al. 2003

Journal of Lipid Research

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A cholesterol-rich emulsion (LDE) that resembles the LDL lipidic structure is taken-up by LDL receptors after intravenous injection by means of apolipoprotein E it acquires in the circulation and can be used to probe LDL metabolism. In this study, LDE was labeled with Emulsions of defined composition resembling the lipidic structure of the plasma lipoproteins are a practical and efficient tool to investigate the lipid intravascular metabolism (1-6). Due to the risk of infection and immune reactions, autologous plasma lipoproteins must be isolated and reinjected into recipient subjects, which is a laborious and time-consuming procedure. In contrast, the same emulsion preparation can be used in an undetermined number of subjects. Furthermore, emulsions are easy to prepare and label with radioactive, fluorescent, or other markers, and bear the advantage of being standard uniform preparations (1-10). In contrast, native lipoproteins comprise different subclasses that vary widely among subjects, each one with distinct biological and pathophysiological properties. All these operational advantages greatly facilitate the execution of systematic studies on the plasma kinetics of lipids. Emulsion models of lymph chylomicrons have been used to clarify the chylomicron metabolism status in several disease states and the action of antilipidemic drugs upon this metabolism (6-10).The metabolism of LDL can also be probed with artificial emulsions (1)(2)(3)(4)(5)(11)(12)(13). In this regard, we have previously studied the metabolic behavior of a cholesterol-rich emulsion termed cholesterol rich emulsion (LDE) that roughly resembles the LDL lipidic structure. LDE is made without protein, but when injected into the blood stream it acquires several small molecular weight apolipoproteins, including apoE (2-3). ApoE endows LDE particles to bind to the LDL receptors, since those receptors recognize not only the apoB present in LDL, but also apoE that is not found in the LDL fraction (14). LDE may be used as a probe to verify LDL intravascular metabolism and removal and LDL receptor function (3-5).The adequacy of LDE as a tool to test in vivo the mechanisms of LDL removal from the plasma was demonstrated in previous clinical studies, wherein the plasma kinetic results obtained with LDE were as expected for native LDL. In this respect, removal of LDE labeled with radioactive cholesteryl esters was slower in patients with familial hypercholesterolemia (4), wherein LDL receptor function is Abbreviations: CAD, coronary artery disease; FCR, fractional catabolic rate; LDE, cholesterol rich emulsion; TLC, thin layer chromatography.

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“…This method has been validated in several studies having unraveled chylomicron metabolism defects in disease states [18][19][20] and under drug treatment. 21 The emulsion is injected intravenously in minimal amounts and in a bolus after a 12 h fasting. By labeling the emulsion with radioactive triglycerides and cholesteryl esters, it is possible to determine in vivo and in an integrated manner the remnant removal process, followed by the kinetics of the emulsion cholesteryl esters and lipolysis that can be estimated by calculating a lipolysis index from both triglyceride and cholesteryl ester kinetics.…”

mentioning

confidence: 99%

Relationships in women between body mass index and the intravascular metabolism of chylomicron-like emulsions

Oliveira

Maranhão

2004

Int J Obes

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OBJECTIVE:To investigate whether increasing body mass index (BMI) produces increasingly intense disturbances in the metabolism of chylomicrons, the lipoproteins that carry the dietary lipids absorbed by the intestine in the circulation. SUBJECTS: Four groups of 10 normolipidemic nondiabetic women at the normal (BMIo25 kg/m 2 ), preobese , obese and morbid obese (BMI440). METHODS: Chylomicron metabolism was studied using the method of triglyceride-rich emulsions that mimic chylomicrons. The chylomicron-like emulsion doubly labeled with 3 H-triolein (TO) and 14 C-cholesteryl-oleate (CO) was intravenously injected to calculate the plasma fractional clearance rates (FCR, in min À1 ) by a compartmental analysis model. FCR-TO mirrors both the lipolysis from lipoprotein lipase that the emulsion suffers while still in the circulation, and the triglycerides portion that is not broken down and is removed from the plasma together with the remnant particles. Lipolysis index is calculated subtracting CO from TO areas under the curve. RESULTS: FCR-TO did not differ among the four groups. The lipolysis index was positively correlated with BMI (r ¼ 0.310; P ¼ 0.05). On the other hand, FCR-CO progressively diminished from the normal to the morbid obese group (0.06970.01; 0.06470.01; 0.03170.003; 0.02970.005 min À1 , respectively, P ¼ 0.003) and there was a negative correlation between FCR-CO and BMI (r ¼ À0.388; P ¼ 0.01). CONCLUSION: In obesity, the capacity to break down chylomicron triglycerides by lipoprotein lipase in vivo increases, but the ability of the organism to remove the resulting chylomicron remnants particles progressively diminishes as the BMI rises. Remnant accumulation most likely predisposes to coronary artery disease development. The increased risk of developing coronary artery diseases in obese subjects may be related, among other causes, to disturbances in the plasma lipoproteins elicited by the weight gain. 1,2 Fasting hypertriglyceridemia is the main dyslipidemia found in obesity. It reflects the plasma accumulation of very-low-density lipoprotein (VLDL), the triglyceride-rich lipoprotein produced by the liver. 3 Low plasma HDL cholesterol may also be found in obese subjects due to the seesaw effect, whereby VLDL and HDL plasma concentration are inversely correlated. 4,5 Owing to the action of transfer proteins, the cholesterol net mass transfer from HDL to VLDL occurs when VLDL concentration increases by mass action law, thus decreasing HDL cholesterol. 5 Furthermore, hepatic lipase is increased in obesity 6 and as this enzyme promotes HDL degradation by the liver, the lipoprotein concentration decreases. 7 Hypertriglyceridemia and low HDL are established risk factors for coronary artery disease. The status in obesity of low-density lipoprotein (LDL) cholesterol is less clear: in some studies it was found increased, while in others it was normal. 1,8 On the other hand, small, dense LDL, which is the LDL subfraction considered as more atherogenic, may be enhanced in obesity. 2

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Effect of Pravastatin on plasma removal of a chylomicron-like emulsion in men with coronary artery disease

Cited by 43 publications

References 20 publications

Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia

Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia

Plasma kinetics of a cholesterol-rich emulsion in subjects with or without coronary artery disease

Relationships in women between body mass index and the intravascular metabolism of chylomicron-like emulsions

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