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

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 [14C]cholesteryl oleate and [3H]cholesterol and injected into 19 patients with coronary artery disease (CAD) and into 14 subjects without CAD to verify whether the kinetic behavior of the radioactive lipids is different in CAD. Blood was sampled over 24 h for radioactivity measurement after lipid extraction and separation by thin-layer chomatography. Fractional clearance rate (FCR, in h−1) of [14C]cholesteryl ester was not different in CAD and nonCAD expressed as median (25%; 75%): 0.08 (0.062; 0.134) h−1 versus 0.06 (0.04; 0.083) h−1, P = 0.167. However, [3H]cholesterol FCR was greater in CAD than in nonCAD (mean ± SEM): 0.163 ± 0.016 h−1 versus 0.077 ± 0.014 h−1, P < 0.001. Esterification of the LDE [3H]cholesterol was also greater in CAD subjects than nonCAD at 10 h and 24 h after emulsion injection (P = 0.029 and 0.024 respectively). In conclusion, both removal from the plasma and esterification of the LDE-cholesterol were increased in CAD.These findings may contribute for unraveling pro-atherogenic mechanisms and the establishment of novel CAD markers. 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 [14C]cholesteryl oleate and [3H]cholesterol and injected into 19 patients with coronary artery disease (CAD) and into 14 subjects without CAD to verify whether the kinetic behavior of the radioactive lipids is different in CAD. Blood was sampled over 24 h for radioactivity measurement after lipid extraction and separation by thin-layer chomatography. Fractional clearance rate (FCR, in h−1) of [14C]cholesteryl ester was not different in CAD and nonCAD expressed as median (25%; 75%): 0.08 (0.062; 0.134) h−1 versus 0.06 (0.04; 0.083) h−1, P = 0.167. However, [3H]cholesterol FCR was greater in CAD than in nonCAD (mean ± SEM): 0.163 ± 0.016 h−1 versus 0.077 ± 0.014 h−1, P < 0.001. Esterification of the LDE [3H]cholesterol was also greater in CAD subjects than nonCAD at 10 h and 24 h after emulsion injection (P = 0.029 and 0.024 respectively). In conclusion, both removal from the plasma and esterification of the LDE-cholesterol were increased in CAD. These findings may contribute for unraveling pro-atherogenic mechanisms and the establishment of novel CAD markers. Emulsions of defined composition resembling the lipidic structure of the plasma lipoproteins are a practical and efficient tool to investigate the lipid intravascular metabolism (1Ginsburg G.S. Small D.M. Atkinson D. Microemulsion of phospholipids and cholesterol esters Protein-free models of low density lipoprotein.J. Biol. Chem. 1982; 257: 8216-8227Google Scholar, 2Maranhão R.C. Cesar T.B. Pedroso-Mariani S.R. Hirata M.H. Mesquita C.H. Metabolic behavior in rats of a nonprotein microemulsion resembling low density lipoprotein.Lipids. 1993; 28: 691-696Google Scholar, 3Maranhão R.C. Garicochea B. Silva E.L. Llacer P.D. Cadoena S.M.S. Coelho I.C. Meneghetti J.C. Pileggi F.J.C. Chamone D.A.F. Plasma kinectics and biodistribution of a lipid emulsion resembling low-density lipoprotein in patients with acute leukemia.Cancer Res. 1994; 54: 4660-4666Google Scholar, 4Maranhão R.C. Roland I.A. Toffoletto O. Ramires J.A. P. Gonçalves R. Mesquita C.H. Pileggi P. Plasma kinetic behavior in hyperlipidemic subjects of a lipidic microemulsion that binds to LDL receptors.Lipids. 1997; 32: 627-633Google Scholar, 5Hirata R.D.C. Hirata M.H. Mesquita C.H. Cesar T.B. Maranhão R.C. Effects of apolipoprotein B-100 on the metabolism of a lipid microemulsio model in rats.Biochim. Biophys. Acta. 1999; 1437: 53-62Google Scholar, 6Maranhão R.C. Feres M.C. Martins M.T. Mesquita C.H. Toffoletto O. Vinagre C.G.C. Gianinni S.D. Pileggi F. Plasma kinetics of a chylomicron-like emulsion in patients with coronary artery disease.Atherosclerosis. 1996; 126: 15-25Google Scholar). 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 (1Ginsburg G.S. Small D.M. Atkinson D. Microemulsion of phospholipids and cholesterol esters Protein-free models of low density lipoprotein.J. Biol. Chem. 1982; 257: 8216-8227Google Scholar, 2Maranhão R.C. Cesar T.B. Pedroso-Mariani S.R. Hirata M.H. Mesquita C.H. Metabolic behavior in rats of a nonprotein microemulsion resembling low density lipoprotein.Lipids. 1993; 28: 691-696Google Scholar, 3Maranhão R.C. Garicochea B. Silva E.L. Llacer P.D. Cadoena S.M.S. Coelho I.C. Meneghetti J.C. Pileggi F.J.C. Chamone D.A.F. Plasma kinectics and biodistribution of a lipid emulsion resembling low-density lipoprotein in patients with acute leukemia.Cancer Res. 1994; 54: 4660-4666Google Scholar, 4Maranhão R.C. Roland I.A. Toffoletto O. Ramires J.A. P. Gonçalves R. Mesquita C.H. Pileggi P. Plasma kinetic behavior in hyperlipidemic subjects of a lipidic microemulsion that binds to LDL receptors.Lipids. 1997; 32: 627-633Google Scholar, 5Hirata R.D.C. Hirata M.H. Mesquita C.H. Cesar T.B. Maranhão R.C. Effects of apolipoprotein B-100 on the metabolism of a lipid microemulsio model in rats.Biochim. Biophys. Acta. 1999; 1437: 53-62Google Scholar, 6Maranhão R.C. Feres M.C. Martins M.T. Mesquita C.H. Toffoletto O. Vinagre C.G.C. Gianinni S.D. Pileggi F. Plasma kinetics of a chylomicron-like emulsion in patients with coronary artery disease.Atherosclerosis. 1996; 126: 15-25Google Scholar, 7Borba E.F. Bonfa E. Vinagre C.G. Ramires J.A. Maranhao R.C. Chylomicron metabolism is markedly altered in systemic lupus erythematosus.Arthritis Rheum. 2000; 43: 1033-1040Google Scholar, 8Vinagre C.G. Stolf N.A. Bocchi E. Maranhao R.C. Chylomicron metabolism in patients submitted to cardiac transplantation.Transplantation. 2000; 69: 532-537Google Scholar, 9Santos R.D. Sposito A.C. Ventura L.I. Cesar L.A. Ramires J.A. Maranhao R.C. Effect of pravastatin on plasma removal of a chylomicron-like emulsion in men with coronary artery disease.Am. J. Cardiol. 2000; 85: 1163-1166Google Scholar, 10Santos R.D. Ventura L.I. Sposito A.C. Schreiber R. Ramires J.A. Maranhao R.C. The effects of gemfibrozil upon the metabolism of chylomicron-like emulsions in patients with endogenous hypertriglyceridemia.Cardiovasc. Res. 2001; 49: 456-465Google Scholar). 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 (6Maranhão R.C. Feres M.C. Martins M.T. Mesquita C.H. Toffoletto O. Vinagre C.G.C. Gianinni S.D. Pileggi F. Plasma kinetics of a chylomicron-like emulsion in patients with coronary artery disease.Atherosclerosis. 1996; 126: 15-25Google Scholar, 7Borba E.F. Bonfa E. Vinagre C.G. Ramires J.A. Maranhao R.C. Chylomicron metabolism is markedly altered in systemic lupus erythematosus.Arthritis Rheum. 2000; 43: 1033-1040Google Scholar, 8Vinagre C.G. Stolf N.A. Bocchi E. Maranhao R.C. Chylomicron metabolism in patients submitted to cardiac transplantation.Transplantation. 2000; 69: 532-537Google Scholar, 9Santos R.D. Sposito A.C. Ventura L.I. Cesar L.A. Ramires J.A. Maranhao R.C. Effect of pravastatin on plasma removal of a chylomicron-like emulsion in men with coronary artery disease.Am. J. Cardiol. 2000; 85: 1163-1166Google Scholar, 10Santos R.D. Ventura L.I. Sposito A.C. Schreiber R. Ramires J.A. Maranhao R.C. The effects of gemfibrozil upon the metabolism of chylomicron-like emulsions in patients with endogenous hypertriglyceridemia.Cardiovasc. Res. 2001; 49: 456-465Google Scholar). The metabolism of LDL can also be probed with artificial emulsions (1Ginsburg G.S. Small D.M. Atkinson D. Microemulsion of phospholipids and cholesterol esters Protein-free models of low density lipoprotein.J. Biol. Chem. 1982; 257: 8216-8227Google Scholar, 2Maranhão R.C. Cesar T.B. Pedroso-Mariani S.R. Hirata M.H. Mesquita C.H. Metabolic behavior in rats of a nonprotein microemulsion resembling low density lipoprotein.Lipids. 1993; 28: 691-696Google Scholar, 3Maranhão R.C. Garicochea B. Silva E.L. Llacer P.D. Cadoena S.M.S. Coelho I.C. Meneghetti J.C. Pileggi F.J.C. Chamone D.A.F. Plasma kinectics and biodistribution of a lipid emulsion resembling low-density lipoprotein in patients with acute leukemia.Cancer Res. 1994; 54: 4660-4666Google Scholar, 4Maranhão R.C. Roland I.A. Toffoletto O. Ramires J.A. P. Gonçalves R. Mesquita C.H. Pileggi P. Plasma kinetic behavior in hyperlipidemic subjects of a lipidic microemulsion that binds to LDL receptors.Lipids. 1997; 32: 627-633Google Scholar, 5Hirata R.D.C. Hirata M.H. Mesquita C.H. Cesar T.B. Maranhão R.C. Effects of apolipoprotein B-100 on the metabolism of a lipid microemulsio model in rats.Biochim. Biophys. Acta. 1999; 1437: 53-62Google Scholar, 11Maranhao R.C. Graziani S.R. Yamaguchi N. Melo R.F. Latrilha M.C. Rodrigues D.G. Couto R.D. Schreier R. Buzaid A.C. Association of carmustine with a lipid emulsion: in vitro, in vivo and preliminary studies in cancer patients.Cancer Chemother. Pharmacol. 2002; 49: 487-498Google Scholar, 12Rodrigues D.G. Covolan C.C. Coradi S.T. Barboza R. Maranhao R.C. Use of a cholesterol-rich emulsion that binds to low-density lipoprotein receptors as a vehicle for paclitaxel.J. Pharm. Pharmacol. 2002; 54: 765-772Google Scholar, 13Graziani S.R. Igreja F.A. Hegg R. Meneghetti C. Brandizzi L.I. Barboza R. Amancio R.F. Pinotti J.A. Maranhao R.C. Uptake of a cholesterol-rich emulsion by breast cancer.Gynecol. Oncol. 2002; 85: 493-497Google Scholar). 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 (2Maranhão R.C. Cesar T.B. Pedroso-Mariani S.R. Hirata M.H. Mesquita C.H. Metabolic behavior in rats of a nonprotein microemulsion resembling low density lipoprotein.Lipids. 1993; 28: 691-696Google Scholar, 3Maranhão R.C. Garicochea B. Silva E.L. Llacer P.D. Cadoena S.M.S. Coelho I.C. Meneghetti J.C. Pileggi F.J.C. Chamone D.A.F. Plasma kinectics and biodistribution of a lipid emulsion resembling low-density lipoprotein in patients with acute leukemia.Cancer Res. 1994; 54: 4660-4666Google Scholar). 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 (14Mahley R.W. Innerarity T.L. Lipoprotein receptors and cholesterol homeostasis.Biochim Biophys Acta. 1983; 737: 197-222Google Scholar). LDE may be used as a probe to verify LDL intravascular metabolism and removal and LDL receptor function (3Maranhão R.C. Garicochea B. Silva E.L. Llacer P.D. Cadoena S.M.S. Coelho I.C. Meneghetti J.C. Pileggi F.J.C. Chamone D.A.F. Plasma kinectics and biodistribution of a lipid emulsion resembling low-density lipoprotein in patients with acute leukemia.Cancer Res. 1994; 54: 4660-4666Google Scholar, 4Maranhão R.C. Roland I.A. Toffoletto O. Ramires J.A. P. Gonçalves R. Mesquita C.H. Pileggi P. Plasma kinetic behavior in hyperlipidemic subjects of a lipidic microemulsion that binds to LDL receptors.Lipids. 1997; 32: 627-633Google Scholar, 5Hirata R.D.C. Hirata M.H. Mesquita C.H. Cesar T.B. Maranhão R.C. Effects of apolipoprotein B-100 on the metabolism of a lipid microemulsio model in rats.Biochim. Biophys. Acta. 1999; 1437: 53-62Google Scholar). 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 (4Maranhão R.C. Roland I.A. Toffoletto O. Ramires J.A. P. Gonçalves R. Mesquita C.H. Pileggi P. Plasma kinetic behavior in hyperlipidemic subjects of a lipidic microemulsion that binds to LDL receptors.Lipids. 1997; 32: 627-633Google Scholar), wherein LDL receptor function is defective and accelerated in untreated patients with acute myeloid leukemia (3Maranhão R.C. Garicochea B. Silva E.L. Llacer P.D. Cadoena S.M.S. Coelho I.C. Meneghetti J.C. Pileggi F.J.C. Chamone D.A.F. Plasma kinectics and biodistribution of a lipid emulsion resembling low-density lipoprotein in patients with acute leukemia.Cancer Res. 1994; 54: 4660-4666Google Scholar) due to the LDL receptor upregulation existing in the neoplastic cells (15Ho Y.K. Smith R.G. Brown M.S. Goldstein J.L. Low-density lipoprotein (LDL) receptor in acute leukemia Scholar). after disease by LDE removal due to of the neoplastic cells with receptors with in LDL cholesterol (3Maranhão R.C. Garicochea B. Silva E.L. Llacer P.D. Cadoena S.M.S. Coelho I.C. Meneghetti J.C. Pileggi F.J.C. Chamone D.A.F. Plasma kinectics and biodistribution of a lipid emulsion resembling low-density lipoprotein in patients with acute leukemia.Cancer Res. 1994; 54: 4660-4666Google Scholar). we were to that LDE rate with Silva E.L. Vinagre C.C. Maranhao R.C. Plasma kinetics of a cholesterol-rich emulsion in and 2001; Scholar). also the of LDE to the behavior of the native in several studies it was that the LDL plasma removal with due to the in LDL receptor of on the metabolism of and LDL apolipoprotein B-100 in Res. Scholar). Due to of to LDL receptors that are in several LDE been as a vehicle to neoplastic (3Maranhão R.C. Garicochea B. Silva E.L. Llacer P.D. Cadoena S.M.S. Coelho I.C. Meneghetti J.C. Pileggi F.J.C. Chamone D.A.F. Plasma kinectics and biodistribution of a lipid emulsion resembling low-density lipoprotein in patients with acute leukemia.Cancer Res. 1994; 54: 4660-4666Google Scholar, 11Maranhao R.C. Graziani S.R. Yamaguchi N. Melo R.F. Latrilha M.C. Rodrigues D.G. Couto R.D. Schreier R. Buzaid A.C. Association of carmustine with a lipid emulsion: in vitro, in vivo and preliminary studies in cancer patients.Cancer Chemother. Pharmacol. 2002; 49: 487-498Google Scholar, 12Rodrigues D.G. Covolan C.C. Coradi S.T. Barboza R. Maranhao R.C. Use of a cholesterol-rich emulsion that binds to low-density lipoprotein receptors as a vehicle for paclitaxel.J. Pharm. Pharmacol. 2002; 54: 765-772Google Scholar, 13Graziani S.R. Igreja F.A. Hegg R. Meneghetti C. Brandizzi L.I. Barboza R. Amancio R.F. Pinotti J.A. Maranhao R.C. Uptake of a cholesterol-rich emulsion by breast cancer.Gynecol. Oncol. 2002; 85: 493-497Google Scholar). In the study, LDE was labeled with radioactive and cholesterol and injected into patients with coronary artery disease (CAD) and into subjects without the disease and with LDL in the same as CAD or of CAD was in the The was to verify whether or not the plasma kinetics of the the The results a for the disease and may in the of the disease The of the were from the of the of the All patients been submitted to coronary that was by to coronary artery disease in the 10 the kinetic The coronary was was to the of this patients were to CAD with on = and nonCAD without on = of the were to or systemic or cardiac or or neoplastic was lipid drugs on the this Blood for of plasma lipids and were after a h on the same the kinetic studies were were used for the of cholesterol and was by the same used for cholesterol after lipoprotein with and were by the of of the of low density lipoprotein cholesterol in without of the Chem. Scholar). Plasma and apoB were by and LDE was from a lipid of cholesteryl and cholesterol from [14C]cholesteryl oleate and [3H]cholesterol from were to the of lipids by in and the of of the emulsion with density by of to LDE microemulsion was by the of (1Ginsburg G.S. Small D.M. Atkinson D. Microemulsion of phospholipids and cholesterol esters Protein-free models of low density lipoprotein.J. Biol. Chem. 1982; 257: 8216-8227Google Scholar) by Maranhão (2Maranhão R.C. Cesar T.B. Pedroso-Mariani S.R. Hirata M.H. Mesquita C.H. Metabolic behavior in rats of a nonprotein microemulsion resembling low density lipoprotein.Lipids. 1993; 28: 691-696Google Scholar). LDE was and for injection into the The were for h at the of the test at but were standard of the at and LDE of [14C]cholesteryl oleate and of [3H]cholesterol in a of in a was injected in a Plasma were 24 in of and and 24 h after the of blood plasma were with at (2Maranhão R.C. Cesar T.B. Pedroso-Mariani S.R. Hirata M.H. Mesquita C.H. Metabolic behavior in rats of a nonprotein microemulsion resembling low density lipoprotein.Lipids. 1993; 28: 691-696Google Scholar). The was to a test and were with of the and for test the were with of and submitted to separation by with a The that to cholesteryl ester and to after being by were and to of was a FCR of the LDE [14C]cholesteryl were to the by The of with plasma Biol. Scholar) as and were from obtained from the radioactivity found in plasma after by the radioactivity plasma in function of a the and the which the FCR in The FCR were from and by the FCR = were the Mesquita C.H. to in and in Chem. Scholar). esterification was to the of to cholesterol at each and and 24 of the radioactivity by the radioactivity after lipid extraction at the cholesterol by that of the cholesterol was by the of test with the which is on the the and the expected Scholar). this the a in plasma and and the [14C]cholesteryl oleate with as as the of [3H]cholesterol FCR and [14C]cholesteryl oleate are expressed as median (25%; The are expressed as ± of the the CAD and nonCAD were by with were and were by the The the FCR of the emulsion with the plasma lipids and was made by the was than one and the was In of P < was All were with the for The was by the of the and a was by The of the radioactive injected into the patients was to the of the on F. In for of by Scholar) as in previous R.C. Graziani S.R. Yamaguchi N. Melo R.F. Latrilha M.C. Rodrigues D.G. Couto R.D. Schreier R. Buzaid A.C. Association of carmustine with a lipid emulsion: in vitro, in vivo and preliminary studies in cancer patients.Cancer Chemother. Pharmacol. 2002; 49: 487-498Google injected on each was the for of F. In for of by Scholar). the and clinical and the plasma of lipids and of the studied subjects. were the and CAD patients (P = and (P = than the nonCAD subjects. was a to in CAD but this not (P = were the and LDL cholesterol and and and standard of the means of plasma lipids and in subjects with CAD or without = = ± ± ± ± ± ± ± ± ± ± ± ± in a [3H]cholesterol FCR was with plasma = P = and with LDL = P = and = P = A was also found [3H]cholesterol FCR and = P = [3H]cholesterol FCR was not with apoB and the only plasma the [3H]cholesterol FCR P = The [14C]cholesteryl ester FCR was not with plasma lipid or apolipoprotein not the plasma of the [14C]cholesteryl oleate of CAD patients and were [14C]cholesteryl oleate 0.08 (0.062; 0.134) h−1 and 0.06 h−1 P = for CAD and The plasma of [3H]cholesterol are in The FCR of [3H]cholesterol was greater in CAD patients than in 0.163 ± 0.016 h−1 versus 0.077 ± 0.014 h−1, P < 0.001. In to the of plasma and in results the of the kinetic was in a of CAD = and nonCAD = subjects for and as in In this CAD patients also greater [3H]cholesterol FCR than that of nonCAD subjects (P = plasma lipids and (FCR, in of the emulsion lipid in subjects with (CAD) or without coronary artery disease by plasma and are means and standard of the = = ± ± ± ± ± ± ± ± ± ± ± ± oleate ± ± in a In studied subjects, the [3H]cholesterol plasma was than that of the [14C]cholesteryl The [3H]cholesterol FCR of the both CAD and nonCAD was h−1, the [14C]cholesteryl oleate was h−1, P = that was a for increased esterification in CAD when with nonCAD in that only at 10 h and 24 h after emulsion injection (P = 0.029 and [3H]cholesterol esterification expressed as means and standard of the in plasma in subjects with CAD or = = ± ± ± ± ± ± ± ± ± ± in a In this study, it was that the removal from the plasma of LDE cholesteryl esters is CAD with nonCAD the removal of LDE is in CAD. In the esterification of the emulsion cholesterol was greater in CAD subjects. to native LDL, LDE is from the plasma R.D.C. Hirata M.H. Mesquita C.H. Cesar T.B. Maranhão R.C. Effects of apolipoprotein B-100 on the metabolism of a lipid microemulsio model in rats.Biochim. Biophys. Acta. 1999; 1437: 53-62Google Scholar). is to the in apolipoprotein on the of those ApoE that binds to LDE been to several greater for the receptor than the LDL J. of low density ester is by apolipoprotein E in Biol. Chem. Scholar). In when was to LDE the injection into the removal from the plasma of the emulsion was markedly R.D.C. Hirata M.H. Mesquita C.H. Cesar T.B. Maranhão R.C. Effects of apolipoprotein B-100 on the metabolism of a lipid microemulsio model in rats.Biochim. Biophys. Acta. 1999; 1437: 53-62Google Scholar). The that LDE is from the plasma than native LDL is a advantage it the for of the plasma kinetics The plasma of LDL is by the the lipoprotein rate and the of removal from the plasma (14Mahley R.W. Innerarity T.L. Lipoprotein receptors and cholesterol homeostasis.Biochim Biophys Acta. 1983; 737: 197-222Google Scholar). LDL the of the lipoprotein and with of LDL. from the plasma and LDL by the are by receptors that recognize M.S. Goldstein J.L. A receptor for cholesterol Scholar). is that of subjects with have different LDL removal by different LDL be to that we in of and subjects Silva E.L. Vinagre C.C. Maranhao R.C. Plasma kinetics of a cholesterol-rich emulsion in and 2001; Scholar). was not different in the but the of LDE was with in and of subjects, LDE removal was greater in the was C.G.C. C.G. Maranhão R.C. on the metabolism of an emulsion to LDL, and on the of cholesterol J. 2001; Scholar). is to that in of subjects with LDL the lipoprotein is to as or increased of low density lipoprotein in patients with coronary artery Cardiol. 2001; Scholar). whether in CAD patients the removal of LDL as with the of LDE be the plasma of the the results of the plasma clearance of the emulsion cholesteryl that the removal of the LDE particles is not different CAD and nonCAD subjects, not be The emulsion cholesteryl ester that the emulsion is the of the LDE particles removal from the plasma (2Maranhão R.C. Cesar T.B. Pedroso-Mariani S.R. Hirata M.H. Mesquita C.H. Metabolic behavior in rats of a nonprotein microemulsion resembling low density lipoprotein.Lipids. 1993; 28: 691-696Google Scholar, 4Maranhão R.C. Roland I.A. Toffoletto O. Ramires J.A. P. Gonçalves R. Mesquita C.H. Pileggi P. Plasma kinetic behavior in hyperlipidemic subjects of a lipidic microemulsion that binds to LDL receptors.Lipids. 1997; 32: 627-633Google Scholar). However, as in native LDL, the emulsion cholesterol ester may to other lipoprotein by the action of the cholesteryl ester ester and plasma lipid 1999; Scholar). is to that are studies in the the plasma kinetics of native LDL in subjects with CAD. In with the cholesteryl cholesterol may from the emulsion to the and the from the emulsion particles not on of lipoproteins in plasma with radioactive for measurement of plasma cholesterol Res. Scholar). In this study, the that the plasma of the emulsion [3H]cholesterol was than that of the [14C]cholesteryl esters in CAD and nonCAD subjects that the cholesterol from the emulsion to the plasma and is than the emulsion in with plasma LDE also and that are also (2Maranhão R.C. Cesar T.B. Pedroso-Mariani S.R. Hirata M.H. Mesquita C.H. Metabolic behavior in rats of a nonprotein microemulsion resembling low density lipoprotein.Lipids. 1993; 28: 691-696Google Scholar, 3Maranhão R.C. Garicochea B. Silva E.L. Llacer P.D. Cadoena S.M.S. Coelho I.C. Meneghetti J.C. Pileggi F.J.C. Chamone D.A.F. Plasma kinectics and biodistribution of a lipid emulsion resembling low-density lipoprotein in patients with acute leukemia.Cancer Res. 1994; 54: 4660-4666Google Scholar). binds to and the esterification of the emulsion cholesterol of cholesterol Res. Scholar). the apolipoprotein in the is from the LDL it also acquires (2Maranhão R.C. Cesar T.B. Pedroso-Mariani S.R. Hirata M.H. Mesquita C.H. Metabolic behavior in rats of a nonprotein microemulsion resembling low density lipoprotein.Lipids. 1993; 28: 691-696Google Scholar, 3Maranhão R.C. Garicochea B. Silva E.L. Llacer P.D. Cadoena S.M.S. Coelho I.C. Meneghetti J.C. Pileggi F.J.C. Chamone D.A.F. Plasma kinectics and biodistribution of a lipid emulsion resembling low-density lipoprotein in patients with acute leukemia.Cancer Res. 1994; 54: 4660-4666Google Scholar), LDE can probe the in vivo esterification of cholesterol in the The plasma of the [3H]cholesterol was in the CAD than in the nonCAD subjects. Furthermore, the esterification was greater in CAD than in nonCAD subjects at 10 h and 24 h after emulsion that the cholesterol from the emulsion and of the plasma in CAD. that the esterification by the emulsion cholesterol is in CAD than in In a study, LDE labeled with [14C]cholesteryl oleate and [3H]cholesterol was injected into CAD patients 24 h the coronary In the of and the of the emulsion [3H]cholesterol was greater than that of the [14C]cholesteryl which the cholesterol from the emulsion particles and in the increased plasma cholesterol esterification in the CAD patients in study, this was also in previous studies by J. esterification in low density lipoprotein and low density Scholar, J. P. J. esterification rate in plasma of low and low density lipoprotein is by the of and in and and Res. Scholar, B. and function of density lipoprotein as an of coronary Cardiol. 1999; Scholar). In those studies, the increased cholesterol esterification was in by cholesterol esterification have been also with increased J. the of may to the of cholesterol Res. Scholar), increased J. The plasma as an with lipoprotein and esterification rate in plasma 2001; Scholar), plasma J. The plasma as an with lipoprotein and esterification rate in plasma 2001; Scholar), and the of small LDL J. the of may to the of cholesterol Res. Scholar), with Small LDL, and the metabolic 1997; Scholar), CAD B. and function of density lipoprotein as an of coronary Cardiol. 1999; Scholar), and that to CAD as R. F. are of cholesterol and in Biol. Scholar, M.H. C. J. Fractional esterification rate of particles in patients with Scholar) and J. P. J. esterification rate in plasma of low and low density lipoprotein is by the of and in and and Res. Scholar). The in vivo in patients of the of an increased plasma cholesterol esterification status a of the emulsion to lipid intravascular metabolism and the of those emulsions to in this metabolism. is that the [3H]cholesterol FCR was with plasma and with the and with in the and with plasma in the those have been to with the of CAD C. J. and risk of 1997; Scholar). the of those with [3H]cholesterol FCR the that this emulsion kinetic be a of the disease and a to the the in [3H]cholesterol FCR the when the for and was which means that were not in this In conclusion, the of LDE as a probe to test the lipoprotein intravascular metabolism of CAD patients that may be present in the disease the cholesterol of lipoprotein removal from the plasma and esterification of cholesterol are These findings may contribute to unraveling of mechanisms and also for the establishment of novel disease markers. was by Maranhão a from the coronary artery disease rate cholesterol rich emulsion