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

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dc.contributor.authorBrulhart-Meynet, Marie-Claudeen_ZA
dc.contributor.authorBraunersreuther, Vincenten_ZA
dc.contributor.authorBrinck, Jonasen_ZA
dc.contributor.authorMontecucco, Fabrizioen_ZA
dc.contributor.authorProst, Jean-Christopheen_ZA
dc.contributor.authorThomas, Aurelienen_ZA
dc.contributor.authorGalan, Katiaen_ZA
dc.contributor.authorPelli, Grazianoen_ZA
dc.contributor.authorPedretti, Sarahen_ZA
dc.contributor.authorVuilleumier, Nicolasen_ZA
dc.date.accessioned2015-11-11T14:26:52Z
dc.date.available2015-11-11T14:26:52Z
dc.date.issued2015en_ZA
dc.description.abstractBACKGROUND: 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.identifier.apacitationBrulhart-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/11427/14918en_ZA
dc.identifier.chicagocitationBrulhart-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/11427/14918en_ZA
dc.identifier.citationBrulhart-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.0119664en_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
dc.identifier.urihttp://hdl.handle.net/11427/14918
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0119664
dc.identifier.vancouvercitationBrulhart-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.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Cardiologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis 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.holder© 2015 Brulhart-Meynet et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherReperfusionen_ZA
dc.subject.otherHearten_ZA
dc.subject.otherIschemiaen_ZA
dc.subject.otherNeutrophilsen_ZA
dc.subject.otherHypoxiaen_ZA
dc.subject.otherInflammationen_ZA
dc.subject.otherPhospholipidsen_ZA
dc.subject.otherReperfusion injuryen_ZA
dc.titleImproving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injuryen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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