Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury

 

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dc.contributor.author Brulhart-Meynet, Marie-Claude en_ZA
dc.contributor.author Braunersreuther, Vincent en_ZA
dc.contributor.author Brinck, Jonas en_ZA
dc.contributor.author Montecucco, Fabrizio en_ZA
dc.contributor.author Prost, Jean-Christophe en_ZA
dc.contributor.author Thomas, Aurelien en_ZA
dc.contributor.author Galan, Katia en_ZA
dc.contributor.author Pelli, Graziano en_ZA
dc.contributor.author Pedretti, Sarah en_ZA
dc.contributor.author Vuilleumier, Nicolas en_ZA
dc.date.accessioned 2015-11-11T14:26:52Z
dc.date.available 2015-11-11T14:26:52Z
dc.date.issued 2015 en_ZA
dc.identifier.citation Brulhart-Meynet, M. C., Braunersreuther, V., Brinck, J., Montecucco, F., Prost, J. C., Thomas, A., ... & Frias, M. A. (2014). Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury. PloS one, 10(3), e0119664. doi:10.1371/journal.pone.0119664 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/14918
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0119664
dc.description.abstract 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights 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 credited. en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other Reperfusion en_ZA
dc.subject.other Heart en_ZA
dc.subject.other Ischemia en_ZA
dc.subject.other Neutrophils en_ZA
dc.subject.other Hypoxia en_ZA
dc.subject.other Inflammation en_ZA
dc.subject.other Phospholipids en_ZA
dc.subject.other Reperfusion injury en_ZA
dc.title Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2015 Brulhart-Meynet et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Cardiology en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Brulhart-Meynet, M., Braunersreuther, V., Brinck, J., Montecucco, F., Prost, J., Thomas, A., ... Vuilleumier, N. (2015). Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury. <i>PLoS One</i>, http://hdl.handle.net/11427/14918 en_ZA
dc.identifier.chicagocitation Brulhart-Meynet, Marie-Claude, Vincent Braunersreuther, Jonas Brinck, Fabrizio Montecucco, Jean-Christophe Prost, Aurelien Thomas, Katia Galan, Graziano Pelli, Sarah Pedretti, and Nicolas Vuilleumier "Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury." <i>PLoS One</i> (2015) http://hdl.handle.net/11427/14918 en_ZA
dc.identifier.vancouvercitation Brulhart-Meynet M, Braunersreuther V, Brinck J, Montecucco F, Prost J, Thomas A, et al. Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury. PLoS One. 2015; http://hdl.handle.net/11427/14918. en_ZA
dc.identifier.ris TY - Journal Article AU - Brulhart-Meynet, Marie-Claude AU - Braunersreuther, Vincent AU - Brinck, Jonas AU - Montecucco, Fabrizio AU - Prost, Jean-Christophe AU - Thomas, Aurelien AU - Galan, Katia AU - Pelli, Graziano AU - Pedretti, Sarah AU - Vuilleumier, Nicolas AB - 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. DA - 2015 DB - OpenUCT DO - 10.1371/journal.pone.0119664 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury TI - Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury UR - http://hdl.handle.net/11427/14918 ER - en_ZA


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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 credited. Except where otherwise noted, this item's license is described as 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 credited.