Alpha-tocopherol acquisition by plasma lipoproteins and changes in lipoprotein profile after cardiac surgery

Alpha-tocopherol, the most abundant form of vitamin E in man, is transported in the circulation by plasma lipoproteins. It plays important roles, not only in preventing lipid peroxidation, but also in modulating several cell functions such as cell signaling and gene expression. While chylomicrons tr...

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Main Author: Hacquebard, Mirjam Rebecca
Other Authors: Carpentier, Yvon
Format: Doctoral Thesis
Language:en
Published: Universite Libre de Bruxelles 2008
Subjects:
Online Access:http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/216586
id ndltd-ulb.ac.be-oai-dipot.ulb.ac.be-2013-216586
record_format oai_dc
collection NDLTD
language en
format Doctoral Thesis
sources NDLTD
topic Médecine pathologie humaine
Heart -- Surgery
Lipoproteins -- Metabolism
Blood lipoproteins -- Metabolism
Coeur -- Chirurgie
Lipoprotéines -- Métabolisme
Lipoprotéines plasmatiques -- Métabolisme
acute phase response
lipoproteins
cardiac surgery
alpha-tocopherol
spellingShingle Médecine pathologie humaine
Heart -- Surgery
Lipoproteins -- Metabolism
Blood lipoproteins -- Metabolism
Coeur -- Chirurgie
Lipoprotéines -- Métabolisme
Lipoprotéines plasmatiques -- Métabolisme
acute phase response
lipoproteins
cardiac surgery
alpha-tocopherol
Hacquebard, Mirjam Rebecca
Alpha-tocopherol acquisition by plasma lipoproteins and changes in lipoprotein profile after cardiac surgery
description Alpha-tocopherol, the most abundant form of vitamin E in man, is transported in the circulation by plasma lipoproteins. It plays important roles, not only in preventing lipid peroxidation, but also in modulating several cell functions such as cell signaling and gene expression. While chylomicrons transport dietary alpha-tocopherol after intestinal absorption, LDL and HDL are the major carriers of alpha-tocopherol in fasting plasma and largely contribute to its delivery to cells and tissues. Exchanges of alpha-tocopherol occur between plasma lipoproteins. In addition, alpha-tocopherol transfers have also been observed, in both directions, between plasma lipoproteins and artificial chylomicrons such as intravenous lipid emulsion particles used in parenteral nutrition. In acute conditions, intravenous supply of vitamin E via lipid emulsions, which bypasses the intestinal tract, may offer some advantages over oral administration to rapidly increase alpha-tocopherol plasma concentration. However, many questions remain unanswered regarding kinetics and factors facilitating vitamin E exchanges between lipid emulsions and plasma lipoproteins. The first part of this work aimed at characterizing alpha-tocopherol transfers between alpha-tocopherol rich emulsion particles and plasma lipoproteins as well as the potential for plasma proteins to modulate such transfers. An in vitro model of incubation was used in which emulsion triglyceride concentration was relatively low and lipoprotein levels comparable to those commonly found in the circulation. Results indicate a high capacity for LDL and HDL to acquire extra-amounts of alpha-tocopherol by rapid mass transfers from alpha-tocopherol-rich emulsion particles. Data further shows that, at a fixed alpha-tocopherol concentration provided by emulsion particles, the limiting factor for alpha-tocopherol enrichment is not the capacity of plasma lipoproteins to accommodate extra-amounts of alpha-tocopherol but the facilitating effect of plasma proteins on alpha-tocopherol transfer, the duration of the incubation and possibly the competition between different acceptor particles. Two lipid transfer proteins, PLTP and CETP, appear to largely mediate facilitation of alpha-tocopherol transfer; however, other plasma proteins may be involved. Data further shows that alpha-tocopherol enriched LDL and HDL can readily transfer newly acquired alpha-tocopherol to cells, without any regulation by plasma proteins.<p>Short-term prophylactic vitamin E supplementation has been suggested to be beneficial in some patients in acute conditions who present reduced plasma vitamin E concentrations in association with important changes in plasma lipids and severe oxidative stress. However, it was not clear whether low plasma vitamin E concentration in critically ill patients is related to changes in the composition of plasma lipoproteins or to a decrease in the number of alpha-tocopherol carriers. In the second part of this work, two clinical studies were conducted to analyze changes of lipoprotein concentration and composition in relation to inflammatory reaction and oxidative stress in selected subgroups of critically ill patients, namely patients undergoing cardiac surgery with different procedures. Important changes in LDL and HDL lipid content were observed, some of which contrast with previous observations made in critically ill septic patients. The reduced plasma level of alpha-tocopherol measured after cardiac surgery is entirely due to a reduced number of circulating LDL and HDL particles. Data suggests that such reduced number in alpha-tocopherol carriers post-surgery may impede the delivery of alpha-tocopherol to cells in conditions of increased requirements due to oxidative stress. Avoidance of extracorporeal circulation during cardiac surgery does not reduce inflammation-related changes in plasma lipids but largely prevents oxidative stress. This data on changes occurring in plasma lipoproteins may help to better define strategies against pro-inflammatory changes or oxidative stress. If further studies would confirm a clinical benefit with evidence-based rationale, alpha-tocopherol enriched lipid emulsions may be used to guarantee a sufficient alpha-tocopherol supply in acute conditions associated with fewer alpha-tocopherol transporters and increased requirements due to high risk of oxidative tissue injury.<p> === Doctorat en Sciences biomédicales et pharmaceutiques === info:eu-repo/semantics/nonPublished
author2 Carpentier, Yvon
author_facet Carpentier, Yvon
Hacquebard, Mirjam Rebecca
author Hacquebard, Mirjam Rebecca
author_sort Hacquebard, Mirjam Rebecca
title Alpha-tocopherol acquisition by plasma lipoproteins and changes in lipoprotein profile after cardiac surgery
title_short Alpha-tocopherol acquisition by plasma lipoproteins and changes in lipoprotein profile after cardiac surgery
title_full Alpha-tocopherol acquisition by plasma lipoproteins and changes in lipoprotein profile after cardiac surgery
title_fullStr Alpha-tocopherol acquisition by plasma lipoproteins and changes in lipoprotein profile after cardiac surgery
title_full_unstemmed Alpha-tocopherol acquisition by plasma lipoproteins and changes in lipoprotein profile after cardiac surgery
title_sort alpha-tocopherol acquisition by plasma lipoproteins and changes in lipoprotein profile after cardiac surgery
publisher Universite Libre de Bruxelles
publishDate 2008
url http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/216586
work_keys_str_mv AT hacquebardmirjamrebecca alphatocopherolacquisitionbyplasmalipoproteinsandchangesinlipoproteinprofileaftercardiacsurgery
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spelling ndltd-ulb.ac.be-oai-dipot.ulb.ac.be-2013-2165862018-04-11T17:37:59Z info:eu-repo/semantics/doctoralThesis info:ulb-repo/semantics/doctoralThesis info:ulb-repo/semantics/openurl/vlink-dissertation Alpha-tocopherol acquisition by plasma lipoproteins and changes in lipoprotein profile after cardiac surgery Hacquebard, Mirjam Rebecca Carpentier, Yvon Rasschaert, Joanne Neve, Jean Ducobu, Jean Sener, Abdullah Delporte, Christine Berger, Mette Universite Libre de Bruxelles Université libre de Bruxelles, Faculté de Médecine – Médecine, Bruxelles 2008-06-30 en Alpha-tocopherol, the most abundant form of vitamin E in man, is transported in the circulation by plasma lipoproteins. It plays important roles, not only in preventing lipid peroxidation, but also in modulating several cell functions such as cell signaling and gene expression. While chylomicrons transport dietary alpha-tocopherol after intestinal absorption, LDL and HDL are the major carriers of alpha-tocopherol in fasting plasma and largely contribute to its delivery to cells and tissues. Exchanges of alpha-tocopherol occur between plasma lipoproteins. In addition, alpha-tocopherol transfers have also been observed, in both directions, between plasma lipoproteins and artificial chylomicrons such as intravenous lipid emulsion particles used in parenteral nutrition. In acute conditions, intravenous supply of vitamin E via lipid emulsions, which bypasses the intestinal tract, may offer some advantages over oral administration to rapidly increase alpha-tocopherol plasma concentration. However, many questions remain unanswered regarding kinetics and factors facilitating vitamin E exchanges between lipid emulsions and plasma lipoproteins. The first part of this work aimed at characterizing alpha-tocopherol transfers between alpha-tocopherol rich emulsion particles and plasma lipoproteins as well as the potential for plasma proteins to modulate such transfers. An in vitro model of incubation was used in which emulsion triglyceride concentration was relatively low and lipoprotein levels comparable to those commonly found in the circulation. Results indicate a high capacity for LDL and HDL to acquire extra-amounts of alpha-tocopherol by rapid mass transfers from alpha-tocopherol-rich emulsion particles. Data further shows that, at a fixed alpha-tocopherol concentration provided by emulsion particles, the limiting factor for alpha-tocopherol enrichment is not the capacity of plasma lipoproteins to accommodate extra-amounts of alpha-tocopherol but the facilitating effect of plasma proteins on alpha-tocopherol transfer, the duration of the incubation and possibly the competition between different acceptor particles. Two lipid transfer proteins, PLTP and CETP, appear to largely mediate facilitation of alpha-tocopherol transfer; however, other plasma proteins may be involved. Data further shows that alpha-tocopherol enriched LDL and HDL can readily transfer newly acquired alpha-tocopherol to cells, without any regulation by plasma proteins.<p>Short-term prophylactic vitamin E supplementation has been suggested to be beneficial in some patients in acute conditions who present reduced plasma vitamin E concentrations in association with important changes in plasma lipids and severe oxidative stress. However, it was not clear whether low plasma vitamin E concentration in critically ill patients is related to changes in the composition of plasma lipoproteins or to a decrease in the number of alpha-tocopherol carriers. In the second part of this work, two clinical studies were conducted to analyze changes of lipoprotein concentration and composition in relation to inflammatory reaction and oxidative stress in selected subgroups of critically ill patients, namely patients undergoing cardiac surgery with different procedures. Important changes in LDL and HDL lipid content were observed, some of which contrast with previous observations made in critically ill septic patients. The reduced plasma level of alpha-tocopherol measured after cardiac surgery is entirely due to a reduced number of circulating LDL and HDL particles. Data suggests that such reduced number in alpha-tocopherol carriers post-surgery may impede the delivery of alpha-tocopherol to cells in conditions of increased requirements due to oxidative stress. Avoidance of extracorporeal circulation during cardiac surgery does not reduce inflammation-related changes in plasma lipids but largely prevents oxidative stress. This data on changes occurring in plasma lipoproteins may help to better define strategies against pro-inflammatory changes or oxidative stress. If further studies would confirm a clinical benefit with evidence-based rationale, alpha-tocopherol enriched lipid emulsions may be used to guarantee a sufficient alpha-tocopherol supply in acute conditions associated with fewer alpha-tocopherol transporters and increased requirements due to high risk of oxidative tissue injury.<p> Médecine pathologie humaine Heart -- Surgery Lipoproteins -- Metabolism Blood lipoproteins -- Metabolism Coeur -- Chirurgie Lipoprotéines -- Métabolisme Lipoprotéines plasmatiques -- Métabolisme acute phase response lipoproteins cardiac surgery alpha-tocopherol 1 v. Doctorat en Sciences biomédicales et pharmaceutiques info:eu-repo/semantics/nonPublished local/bictel.ulb.ac.be:ULBetd-07032008-113258 local/ulbcat.ulb.ac.be:835025 http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/216586 No full-text files