Cargando…
Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury
BACKGROUND: New evidence shows that high density lipoproteins (HDL) have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL) offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion inju...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362758/ https://www.ncbi.nlm.nih.gov/pubmed/25781943 http://dx.doi.org/10.1371/journal.pone.0119664 |
_version_ | 1782361841122410496 |
---|---|
author | Brulhart-Meynet, Marie-Claude Braunersreuther, Vincent Brinck, Jonas Montecucco, Fabrizio Prost, Jean-Christophe Thomas, Aurelien Galan, Katia Pelli, Graziano Pedretti, Sarah Vuilleumier, Nicolas Mach, François Lecour, Sandrine James, Richard W. Frias, Miguel A. |
author_facet | Brulhart-Meynet, Marie-Claude Braunersreuther, Vincent Brinck, Jonas Montecucco, Fabrizio Prost, Jean-Christophe Thomas, Aurelien Galan, Katia Pelli, Graziano Pedretti, Sarah Vuilleumier, Nicolas Mach, François Lecour, Sandrine James, Richard W. Frias, Miguel A. |
author_sort | Brulhart-Meynet, Marie-Claude |
collection | PubMed |
description | BACKGROUND: New evidence shows that high density lipoproteins (HDL) have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL) offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion injury (IRI). However, basic rHDL composition is limited to apolipoprotein AI (apoAI) and phospholipids; addition of bioactive compound may enhance its beneficial effects. OBJECTIVE: The aim of this study was to investigate the role of rHDL in post-ischemic model, and to analyze the potential impact of sphingosine-1-phosphate (S1P) in rHDL formulations. METHODS AND RESULTS: The impact of HDL on IRI was investigated using complementary in vivo, ex vivo and in vitro IRI models. Acute post-ischemic treatment with native HDL significantly reduced infarct size and cell death in the ex vivo, isolated heart (Langendorff) model and the in vivo model (-48%, p<0.01). Treatment with rHDL of basic formulation (apoAI + phospholipids) had a non-significant impact on cell death in vitro and on the infarct size ex vivo and in vivo. In contrast, rHDL containing S1P had a highly significant, protective influence ex vivo, and in vivo (-50%, p<0.01). This impact was comparable with the effects observed with native HDL. Pro-survival signaling proteins, Akt, STAT3 and ERK1/2 were similarly activated by HDL and rHDL containing S1P both in vitro (isolated cardiomyocytes) and in vivo. CONCLUSION: HDL afford protection against IRI in a clinically relevant model (post-ischemia). rHDL is significantly protective if supplemented with S1P. The protective impact of HDL appears to target directly the cardiomyocyte. |
format | Online Article Text |
id | pubmed-4362758 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43627582015-03-23 Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury Brulhart-Meynet, Marie-Claude Braunersreuther, Vincent Brinck, Jonas Montecucco, Fabrizio Prost, Jean-Christophe Thomas, Aurelien Galan, Katia Pelli, Graziano Pedretti, Sarah Vuilleumier, Nicolas Mach, François Lecour, Sandrine James, Richard W. Frias, Miguel A. PLoS One Research Article BACKGROUND: New evidence shows that high density lipoproteins (HDL) have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL) offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion injury (IRI). However, basic rHDL composition is limited to apolipoprotein AI (apoAI) and phospholipids; addition of bioactive compound may enhance its beneficial effects. OBJECTIVE: The aim of this study was to investigate the role of rHDL in post-ischemic model, and to analyze the potential impact of sphingosine-1-phosphate (S1P) in rHDL formulations. METHODS AND RESULTS: The impact of HDL on IRI was investigated using complementary in vivo, ex vivo and in vitro IRI models. Acute post-ischemic treatment with native HDL significantly reduced infarct size and cell death in the ex vivo, isolated heart (Langendorff) model and the in vivo model (-48%, p<0.01). Treatment with rHDL of basic formulation (apoAI + phospholipids) had a non-significant impact on cell death in vitro and on the infarct size ex vivo and in vivo. In contrast, rHDL containing S1P had a highly significant, protective influence ex vivo, and in vivo (-50%, p<0.01). This impact was comparable with the effects observed with native HDL. Pro-survival signaling proteins, Akt, STAT3 and ERK1/2 were similarly activated by HDL and rHDL containing S1P both in vitro (isolated cardiomyocytes) and in vivo. CONCLUSION: HDL afford protection against IRI in a clinically relevant model (post-ischemia). rHDL is significantly protective if supplemented with S1P. The protective impact of HDL appears to target directly the cardiomyocyte. Public Library of Science 2015-03-17 /pmc/articles/PMC4362758/ /pubmed/25781943 http://dx.doi.org/10.1371/journal.pone.0119664 Text en © 2015 Brulhart-Meynet et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Brulhart-Meynet, Marie-Claude Braunersreuther, Vincent Brinck, Jonas Montecucco, Fabrizio Prost, Jean-Christophe Thomas, Aurelien Galan, Katia Pelli, Graziano Pedretti, Sarah Vuilleumier, Nicolas Mach, François Lecour, Sandrine James, Richard W. Frias, Miguel A. Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury |
title | Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury |
title_full | Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury |
title_fullStr | Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury |
title_full_unstemmed | Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury |
title_short | Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury |
title_sort | improving reconstituted hdl composition for efficient post-ischemic reduction of ischemia reperfusion injury |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362758/ https://www.ncbi.nlm.nih.gov/pubmed/25781943 http://dx.doi.org/10.1371/journal.pone.0119664 |
work_keys_str_mv | AT brulhartmeynetmarieclaude improvingreconstitutedhdlcompositionforefficientpostischemicreductionofischemiareperfusioninjury AT braunersreuthervincent improvingreconstitutedhdlcompositionforefficientpostischemicreductionofischemiareperfusioninjury AT brinckjonas improvingreconstitutedhdlcompositionforefficientpostischemicreductionofischemiareperfusioninjury AT montecuccofabrizio improvingreconstitutedhdlcompositionforefficientpostischemicreductionofischemiareperfusioninjury AT prostjeanchristophe improvingreconstitutedhdlcompositionforefficientpostischemicreductionofischemiareperfusioninjury AT thomasaurelien improvingreconstitutedhdlcompositionforefficientpostischemicreductionofischemiareperfusioninjury AT galankatia improvingreconstitutedhdlcompositionforefficientpostischemicreductionofischemiareperfusioninjury AT pelligraziano improvingreconstitutedhdlcompositionforefficientpostischemicreductionofischemiareperfusioninjury AT pedrettisarah improvingreconstitutedhdlcompositionforefficientpostischemicreductionofischemiareperfusioninjury AT vuilleumiernicolas improvingreconstitutedhdlcompositionforefficientpostischemicreductionofischemiareperfusioninjury AT machfrancois improvingreconstitutedhdlcompositionforefficientpostischemicreductionofischemiareperfusioninjury AT lecoursandrine improvingreconstitutedhdlcompositionforefficientpostischemicreductionofischemiareperfusioninjury AT jamesrichardw improvingreconstitutedhdlcompositionforefficientpostischemicreductionofischemiareperfusioninjury AT friasmiguela improvingreconstitutedhdlcompositionforefficientpostischemicreductionofischemiareperfusioninjury |