Deposition of Free Cholesterol in the Blood Vessels of Patients with Coronary Artery Disease: a Possible Novel Mechanism for Atherogenesis |
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Authors: | Ricardo D Couto Luís A O Dallan Luiz A F Lisboa Carlos H Mesquita Carmen G C Vinagre Raul C Maranhão |
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Affiliation: | 1.Lipid Metabolism Laboratory and the Surgical Division, The Heart Institute (INCOR) of the Medical School Hospital,University of S?o Paulo,Sao Paulo,Brazil;2.Faculty of Pharmaceutical Sciences,University of S?o Paulo,Sao Paulo,Brazil;3.Instituto do Cora??o (InCor) do Hospital das Clínicas da USP, Laboratório de Metabolismo de Lípides,Sao Paulo-SP,Brazil |
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Abstract: | A cholesterol-rich nanoemulsion (LDE) that mimics the composition of low-density lipoprotein (LDL) acquires apoE in the plasma
and is taken-up by the cells by LDL receptors. In this study, to verify whether free cholesterol (FC) and the cholesteryl
ester (CE) components of LDL are taken-up differently by the vessels. LDE labeled with 3H-cholesterol and 14C-cholesteryl oleate was injected into 20 coronary artery disease patients 24 h before a scheduled myocardial coronary artery
bypass grafting. The plasma kinetics of both radiolabels was determined from plasma samples collected over 24 h, and fragments
of vessels discarded during surgery were collected and analyzed for radioactivity. LDE FC was removed faster than CE. The
radioactive counting of LDE CE was greater than that of LDE FC in the blood, but the uptake of FC was markedly greater than
that of CE in all fragments: fivefold greater in the aorta (p = 0.04), fourfold greater in the internal thoracic artery (p = 0.03), tenfold greater in the saphenous vein (p = 0.01) and threefold in the radial artery (p = 0.05). In conclusion, the greater removal from plasma of FC compared with CE and the remarkably greater vessel tissue uptake
of FC compared with CE suggests that, in the plasma, FC dissociates from the nanoemulsion particles and precipitates in the
vessels. Considering LDE as an artificial nanoemulsion model for LDL, our results suggest that dissociation of FC from lipoprotein
particles and deposition in the vessel wall may play a role as an independent mechanism in atherogenesis. |
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Keywords: | LDL metabolism Nanoparticles Emulsions Lipids and atherosclerosis Free cholesterol Cholesteryl esters Coronary artery disease Lipoproteins Lipoprotein kinetics |
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