GlutaredoxinV1, Main, Exploration, bibRecord, 000303

The NRF2 activator DH404 attenuates adverse ventricular remodeling post-myocardial infarction by modifying redox signalling.

Identifieur interne : 000303 ( Main/Exploration ); précédent : 000302; suivant : 000304

The NRF2 activator DH404 attenuates adverse ventricular remodeling post-myocardial infarction by modifying redox signalling.

Auteurs : Kristen J. Bubb [Australie] ; Cindy Kok [Australie] ; Owen Tang [Australie] ; Nathalie B. Rasko [Australie] ; Asa B. Birgisdottir [Norvège] ; Thomas Hansen [Australie] ; Rebecca Ritchie [Australie] ; Ravinay Bhindi [Australie] ; Scott A. Reisman [États-Unis] ; Colin Meyer [États-Unis] ; Keith Ward [États-Unis] ; Keyvan Karimi Galougahi [Australie] ; Gemma A. Figtree [Australie]

Source :

Free radical biology & medicine [ 1873-4596 ] ; 2017.

RBID : pubmed:28438659

Descripteurs français

KwdFr :
- Acide oléanolique (analogues et dérivés), Acide oléanolique (composition chimique), Acide oléanolique (usage thérapeutique), Angiotensine-II (métabolisme), Animaux (MeSH), Cellules cultivées (MeSH), Coeur (effets des médicaments et des substances chimiques), Coeur (physiologie), Facteur atrial natriurétique (métabolisme), Facteur-2 apparenté à NF-E2 (métabolisme), Fibronectines (métabolisme), Glutarédoxines (génétique), Glutarédoxines (métabolisme), Humains (MeSH), Infarctus du myocarde (traitement médicamenteux), Modèles animaux de maladie humaine (MeSH), Mâle (MeSH), Nitric oxide synthase type III (métabolisme), Oxydoréduction (MeSH), Petit ARN interférent (génétique), Rat Sprague-Dawley (MeSH), Rats (MeSH), Remodelage ventriculaire (effets des médicaments et des substances chimiques), Transduction du signal (MeSH).
MESH :
- analogues et dérivés : Acide oléanolique.
- composition chimique : Acide oléanolique.
- effets des médicaments et des substances chimiques : Coeur, Remodelage ventriculaire.
- génétique : Glutarédoxines, Petit ARN interférent.
- métabolisme : Angiotensine-II, Facteur atrial natriurétique, Facteur-2 apparenté à NF-E2, Fibronectines, Glutarédoxines, Nitric oxide synthase type III.
- physiologie : Coeur.
- traitement médicamenteux : Infarctus du myocarde.
- usage thérapeutique : Acide oléanolique.
- Animaux, Cellules cultivées, Humains, Modèles animaux de maladie humaine, Mâle, Oxydoréduction, Rat Sprague-Dawley, Rats, Transduction du signal.

English descriptors

KwdEn :
- Angiotensin II (metabolism), Animals (MeSH), Atrial Natriuretic Factor (metabolism), Cells, Cultured (MeSH), Disease Models, Animal (MeSH), Fibronectins (metabolism), Glutaredoxins (genetics), Glutaredoxins (metabolism), Heart (drug effects), Heart (physiology), Humans (MeSH), Male (MeSH), Myocardial Infarction (drug therapy), NF-E2-Related Factor 2 (metabolism), Nitric Oxide Synthase Type III (metabolism), Oleanolic Acid (analogs & derivatives), Oleanolic Acid (chemistry), Oleanolic Acid (therapeutic use), Oxidation-Reduction (MeSH), RNA, Small Interfering (genetics), Rats (MeSH), Rats, Sprague-Dawley (MeSH), Signal Transduction (MeSH), Ventricular Remodeling (drug effects).
MESH :
- chemical , analogs & derivatives : Oleanolic Acid.
- chemical , chemistry : Oleanolic Acid.
- chemical , genetics : Glutaredoxins, RNA, Small Interfering.
- chemical , metabolism : Angiotensin II, Atrial Natriuretic Factor, Fibronectins, Glutaredoxins, NF-E2-Related Factor 2, Nitric Oxide Synthase Type III.
- drug effects : Heart, Ventricular Remodeling.
- drug therapy : Myocardial Infarction.
- physiology : Heart.
- chemical , therapeutic use : Oleanolic Acid.
- Animals, Cells, Cultured, Disease Models, Animal, Humans, Male, Oxidation-Reduction, Rats, Rats, Sprague-Dawley, Signal Transduction.

Abstract

BACKGROUND

The novel synthetic triterpenoid, bardoxolone methyl, has the ability to upregulate cytoprotective proteins via induction of the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. This makes it a promising therapeutic agent in disease states characterized by dysregulated oxidative signalling. We have examined the effect of a Nrf2 activator, dihydro-CDDO-trifluoroethyl amide (DH404), a derivative of bardoxolone methyl, on post-infarct cardiac remodeling in rats.

METHODS/RESULTS

DH404, administered from day 2 post myocardial infarction (MI: 30min transient ischemia followed by reperfusion) resulted in almost complete protection against adverse ventricular remodeling as assessed at day 28 (left ventricular end-systolic area: sham 0.14±0.01cm

CONCLUSION

The bardoxolone derivative DH404 significantly attenuated cardiac remodeling post MI, at least in part, by re-coupling of eNOS and increasing the functional interaction of Grx1 with eNOS. This agent may have clinical benefits protecting against post MI cardiomyopathy.

DOI: 10.1016/j.freeradbiomed.2017.04.027
PubMed: 28438659

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000349
to stream Main, to step Curation: 000349

Le document en format XML

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<author><name sortKey="Bhindi, Ravinay" sort="Bhindi, Ravinay" uniqKey="Bhindi R" first="Ravinay" last="Bhindi">Ravinay Bhindi</name>
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<author><name sortKey="Reisman, Scott A" sort="Reisman, Scott A" uniqKey="Reisman S" first="Scott A" last="Reisman">Scott A. Reisman</name>
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<author><name sortKey="Ward, Keith" sort="Ward, Keith" uniqKey="Ward K" first="Keith" last="Ward">Keith Ward</name>
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<author><name sortKey="Karimi Galougahi, Keyvan" sort="Karimi Galougahi, Keyvan" uniqKey="Karimi Galougahi K" first="Keyvan" last="Karimi Galougahi">Keyvan Karimi Galougahi</name>
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<country xml:lang="fr">Australie</country>
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<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Figtree, Gemma A" sort="Figtree, Gemma A" uniqKey="Figtree G" first="Gemma A" last="Figtree">Gemma A. Figtree</name>
<affiliation wicri:level="4"><nlm:affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia; Department of Cardiology, Royal North Shore Hospital and University of Sydney, Australia. Electronic address: gemma.figtree@sydney.edu.au.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia; Department of Cardiology, Royal North Shore Hospital and University of Sydney</wicri:regionArea>
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<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
<orgName type="university">Université de Sydney</orgName>
</affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">The NRF2 activator DH404 attenuates adverse ventricular remodeling post-myocardial infarction by modifying redox signalling.</title>
<author><name sortKey="Bubb, Kristen J" sort="Bubb, Kristen J" uniqKey="Bubb K" first="Kristen J" last="Bubb">Kristen J. Bubb</name>
<affiliation wicri:level="3"><nlm:affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kok, Cindy" sort="Kok, Cindy" uniqKey="Kok C" first="Cindy" last="Kok">Cindy Kok</name>
<affiliation wicri:level="3"><nlm:affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tang, Owen" sort="Tang, Owen" uniqKey="Tang O" first="Owen" last="Tang">Owen Tang</name>
<affiliation wicri:level="3"><nlm:affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rasko, Nathalie B" sort="Rasko, Nathalie B" uniqKey="Rasko N" first="Nathalie B" last="Rasko">Nathalie B. Rasko</name>
<affiliation wicri:level="3"><nlm:affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Birgisdottir, Asa B" sort="Birgisdottir, Asa B" uniqKey="Birgisdottir A" first="Asa B" last="Birgisdottir">Asa B. Birgisdottir</name>
<affiliation wicri:level="1"><nlm:affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia; Department of Cardiothoracic and Vascular Surgery, Heart and Lung Clinic, University Hospital of North Norway, Tromsø, Norway.</nlm:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia; Department of Cardiothoracic and Vascular Surgery, Heart and Lung Clinic, University Hospital of North Norway, Tromsø</wicri:regionArea>
<wicri:noRegion>Tromsø</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hansen, Thomas" sort="Hansen, Thomas" uniqKey="Hansen T" first="Thomas" last="Hansen">Thomas Hansen</name>
<affiliation wicri:level="3"><nlm:affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ritchie, Rebecca" sort="Ritchie, Rebecca" uniqKey="Ritchie R" first="Rebecca" last="Ritchie">Rebecca Ritchie</name>
<affiliation wicri:level="3"><nlm:affiliation>Baker IDI Heart and Diabetes Institute, Melbourne, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Baker IDI Heart and Diabetes Institute, Melbourne</wicri:regionArea>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bhindi, Ravinay" sort="Bhindi, Ravinay" uniqKey="Bhindi R" first="Ravinay" last="Bhindi">Ravinay Bhindi</name>
<affiliation wicri:level="4"><nlm:affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia; Department of Cardiology, Royal North Shore Hospital and University of Sydney, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia; Department of Cardiology, Royal North Shore Hospital and University of Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
<orgName type="university">Université de Sydney</orgName>
</affiliation>
</author>
<author><name sortKey="Reisman, Scott A" sort="Reisman, Scott A" uniqKey="Reisman S" first="Scott A" last="Reisman">Scott A. Reisman</name>
<affiliation wicri:level="2"><nlm:affiliation>Reata Pharmaceuticals, Inc. Irving, TX, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Reata Pharmaceuticals, Inc. Irving, TX</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Meyer, Colin" sort="Meyer, Colin" uniqKey="Meyer C" first="Colin" last="Meyer">Colin Meyer</name>
<affiliation wicri:level="2"><nlm:affiliation>Reata Pharmaceuticals, Inc. Irving, TX, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Reata Pharmaceuticals, Inc. Irving, TX</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ward, Keith" sort="Ward, Keith" uniqKey="Ward K" first="Keith" last="Ward">Keith Ward</name>
<affiliation wicri:level="2"><nlm:affiliation>Reata Pharmaceuticals, Inc. Irving, TX, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Reata Pharmaceuticals, Inc. Irving, TX</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Karimi Galougahi, Keyvan" sort="Karimi Galougahi, Keyvan" uniqKey="Karimi Galougahi K" first="Keyvan" last="Karimi Galougahi">Keyvan Karimi Galougahi</name>
<affiliation wicri:level="3"><nlm:affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Figtree, Gemma A" sort="Figtree, Gemma A" uniqKey="Figtree G" first="Gemma A" last="Figtree">Gemma A. Figtree</name>
<affiliation wicri:level="4"><nlm:affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia; Department of Cardiology, Royal North Shore Hospital and University of Sydney, Australia. Electronic address: gemma.figtree@sydney.edu.au.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia; Department of Cardiology, Royal North Shore Hospital and University of Sydney</wicri:regionArea>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
<orgName type="university">Université de Sydney</orgName>
</affiliation>
</author>
</analytic>
<series><title level="j">Free radical biology & medicine</title>
<idno type="eISSN">1873-4596</idno>
<imprint><date when="2017" type="published">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Angiotensin II (metabolism)</term>
<term>Animals (MeSH)</term>
<term>Atrial Natriuretic Factor (metabolism)</term>
<term>Cells, Cultured (MeSH)</term>
<term>Disease Models, Animal (MeSH)</term>
<term>Fibronectins (metabolism)</term>
<term>Glutaredoxins (genetics)</term>
<term>Glutaredoxins (metabolism)</term>
<term>Heart (drug effects)</term>
<term>Heart (physiology)</term>
<term>Humans (MeSH)</term>
<term>Male (MeSH)</term>
<term>Myocardial Infarction (drug therapy)</term>
<term>NF-E2-Related Factor 2 (metabolism)</term>
<term>Nitric Oxide Synthase Type III (metabolism)</term>
<term>Oleanolic Acid (analogs & derivatives)</term>
<term>Oleanolic Acid (chemistry)</term>
<term>Oleanolic Acid (therapeutic use)</term>
<term>Oxidation-Reduction (MeSH)</term>
<term>RNA, Small Interfering (genetics)</term>
<term>Rats (MeSH)</term>
<term>Rats, Sprague-Dawley (MeSH)</term>
<term>Signal Transduction (MeSH)</term>
<term>Ventricular Remodeling (drug effects)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Acide oléanolique (analogues et dérivés)</term>
<term>Acide oléanolique (composition chimique)</term>
<term>Acide oléanolique (usage thérapeutique)</term>
<term>Angiotensine-II (métabolisme)</term>
<term>Animaux (MeSH)</term>
<term>Cellules cultivées (MeSH)</term>
<term>Coeur (effets des médicaments et des substances chimiques)</term>
<term>Coeur (physiologie)</term>
<term>Facteur atrial natriurétique (métabolisme)</term>
<term>Facteur-2 apparenté à NF-E2 (métabolisme)</term>
<term>Fibronectines (métabolisme)</term>
<term>Glutarédoxines (génétique)</term>
<term>Glutarédoxines (métabolisme)</term>
<term>Humains (MeSH)</term>
<term>Infarctus du myocarde (traitement médicamenteux)</term>
<term>Modèles animaux de maladie humaine (MeSH)</term>
<term>Mâle (MeSH)</term>
<term>Nitric oxide synthase type III (métabolisme)</term>
<term>Oxydoréduction (MeSH)</term>
<term>Petit ARN interférent (génétique)</term>
<term>Rat Sprague-Dawley (MeSH)</term>
<term>Rats (MeSH)</term>
<term>Remodelage ventriculaire (effets des médicaments et des substances chimiques)</term>
<term>Transduction du signal (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Oleanolic Acid</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Oleanolic Acid</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Glutaredoxins</term>
<term>RNA, Small Interfering</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Angiotensin II</term>
<term>Atrial Natriuretic Factor</term>
<term>Fibronectins</term>
<term>Glutaredoxins</term>
<term>NF-E2-Related Factor 2</term>
<term>Nitric Oxide Synthase Type III</term>
</keywords>
<keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Acide oléanolique</term>
</keywords>
<keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Acide oléanolique</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Heart</term>
<term>Ventricular Remodeling</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Myocardial Infarction</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Coeur</term>
<term>Remodelage ventriculaire</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glutarédoxines</term>
<term>Petit ARN interférent</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Angiotensine-II</term>
<term>Facteur atrial natriurétique</term>
<term>Facteur-2 apparenté à NF-E2</term>
<term>Fibronectines</term>
<term>Glutarédoxines</term>
<term>Nitric oxide synthase type III</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coeur</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Heart</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Oleanolic Acid</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infarctus du myocarde</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Acide oléanolique</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cells, Cultured</term>
<term>Disease Models, Animal</term>
<term>Humans</term>
<term>Male</term>
<term>Oxidation-Reduction</term>
<term>Rats</term>
<term>Rats, Sprague-Dawley</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules cultivées</term>
<term>Humains</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mâle</term>
<term>Oxydoréduction</term>
<term>Rat Sprague-Dawley</term>
<term>Rats</term>
<term>Transduction du signal</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b>
</p>
<p>The novel synthetic triterpenoid, bardoxolone methyl, has the ability to upregulate cytoprotective proteins via induction of the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. This makes it a promising therapeutic agent in disease states characterized by dysregulated oxidative signalling. We have examined the effect of a Nrf2 activator, dihydro-CDDO-trifluoroethyl amide (DH404), a derivative of bardoxolone methyl, on post-infarct cardiac remodeling in rats.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>METHODS/RESULTS</b>
</p>
<p>DH404, administered from day 2 post myocardial infarction (MI: 30min transient ischemia followed by reperfusion) resulted in almost complete protection against adverse ventricular remodeling as assessed at day 28 (left ventricular end-systolic area: sham 0.14±0.01cm</p>
</div>
<div type="abstract" xml:lang="en"><p><b>CONCLUSION</b>
</p>
<p>The bardoxolone derivative DH404 significantly attenuated cardiac remodeling post MI, at least in part, by re-coupling of eNOS and increasing the functional interaction of Grx1 with eNOS. This agent may have clinical benefits protecting against post MI cardiomyopathy.</p>
</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28438659</PMID>
<DateCompleted><Year>2018</Year>
<Month>04</Month>
<Day>09</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>04</Month>
<Day>10</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-4596</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>108</Volume>
<PubDate><Year>2017</Year>
<Month>07</Month>
</PubDate>
</JournalIssue>
<Title>Free radical biology & medicine</Title>
<ISOAbbreviation>Free Radic Biol Med</ISOAbbreviation>
</Journal>
<ArticleTitle>The NRF2 activator DH404 attenuates adverse ventricular remodeling post-myocardial infarction by modifying redox signalling.</ArticleTitle>
<Pagination><MedlinePgn>585-594</MedlinePgn>
</Pagination>
<ELocationID EIdType="pii" ValidYN="Y">S0891-5849(17)30230-7</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.freeradbiomed.2017.04.027</ELocationID>
<Abstract><AbstractText Label="BACKGROUND">The novel synthetic triterpenoid, bardoxolone methyl, has the ability to upregulate cytoprotective proteins via induction of the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. This makes it a promising therapeutic agent in disease states characterized by dysregulated oxidative signalling. We have examined the effect of a Nrf2 activator, dihydro-CDDO-trifluoroethyl amide (DH404), a derivative of bardoxolone methyl, on post-infarct cardiac remodeling in rats.</AbstractText>
<AbstractText Label="METHODS/RESULTS">DH404, administered from day 2 post myocardial infarction (MI: 30min transient ischemia followed by reperfusion) resulted in almost complete protection against adverse ventricular remodeling as assessed at day 28 (left ventricular end-systolic area: sham 0.14±0.01cm<sup>2</sup>
, MI vehicle 0.29±0.04cm<sup>2</sup>
 vs. MI DH404 0.18±0.02cm<sup>2</sup>
, P<0.05); infarct size (21.3±3.4% MI vehicle vs. 10.9±2.3% MI DH404, P<0.05) with associated benefits on systolic function (fractional shortening: sham 71.9±2.6%, MI vehicle 36.2±1.9% vs. MI DH404 58.6±4.0%, P<0.05). These structural and functional benefits were associated with lower myocardial expression of atrial natriuretic peptide (ANP, P<0.01 vs. MI vehicle), and decreased fibronectin (P<0.01 vs. MI vehicle) in DH404-treated MI rats at 28 days. MI increased glutathionylation of endothelial nitric oxide synthase (eNOS) in vitro - a molecular switch that uncouples the enzyme, increasing superoxide production and decreasing nitric oxide (NO) bioavailability. MI-induced eNOS glutathionylation was substantially ameliorated by DH404. An associated increase in glutaredoxin 1 (Grx1) co-immunoprecipitation with eNOS without a change in expression was mechanistically intriguing. Indeed, in parallel in vitro experiments, silencing of Grx1 abolished the protective effect of DH404 against Angiotensin II-induced eNOS uncoupling.</AbstractText>
<AbstractText Label="CONCLUSION">The bardoxolone derivative DH404 significantly attenuated cardiac remodeling post MI, at least in part, by re-coupling of eNOS and increasing the functional interaction of Grx1 with eNOS. This agent may have clinical benefits protecting against post MI cardiomyopathy.</AbstractText>
<CopyrightInformation>Copyright © 2017. Published by Elsevier Inc.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bubb</LastName>
<ForeName>Kristen J</ForeName>
<Initials>KJ</Initials>
<AffiliationInfo><Affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kok</LastName>
<ForeName>Cindy</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tang</LastName>
<ForeName>Owen</ForeName>
<Initials>O</Initials>
<AffiliationInfo><Affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rasko</LastName>
<ForeName>Nathalie B</ForeName>
<Initials>NB</Initials>
<AffiliationInfo><Affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Birgisdottir</LastName>
<ForeName>Asa B</ForeName>
<Initials>AB</Initials>
<AffiliationInfo><Affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia; Department of Cardiothoracic and Vascular Surgery, Heart and Lung Clinic, University Hospital of North Norway, Tromsø, Norway.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hansen</LastName>
<ForeName>Thomas</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ritchie</LastName>
<ForeName>Rebecca</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Baker IDI Heart and Diabetes Institute, Melbourne, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bhindi</LastName>
<ForeName>Ravinay</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia; Department of Cardiology, Royal North Shore Hospital and University of Sydney, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Reisman</LastName>
<ForeName>Scott A</ForeName>
<Initials>SA</Initials>
<AffiliationInfo><Affiliation>Reata Pharmaceuticals, Inc. Irving, TX, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Meyer</LastName>
<ForeName>Colin</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Reata Pharmaceuticals, Inc. Irving, TX, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ward</LastName>
<ForeName>Keith</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Reata Pharmaceuticals, Inc. Irving, TX, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Karimi Galougahi</LastName>
<ForeName>Keyvan</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Figtree</LastName>
<ForeName>Gemma A</ForeName>
<Initials>GA</Initials>
<AffiliationInfo><Affiliation>North Shore Heart Research Group, Kolling Institute, University of Sydney and Royal North Shore Hospital, Sydney, Australia; Department of Cardiology, Royal North Shore Hospital and University of Sydney, Australia. Electronic address: gemma.figtree@sydney.edu.au.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>04</Month>
<Day>21</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Free Radic Biol Med</MedlineTA>
<NlmUniqueID>8709159</NlmUniqueID>
<ISSNLinking>0891-5849</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D005353">Fibronectins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D054477">Glutaredoxins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D051267">NF-E2-Related Factor 2</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C495637">Nfe2l2 protein, rat</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D034741">RNA, Small Interfering</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C547749">dh404 compound</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>11128-99-7</RegistryNumber>
<NameOfSubstance UI="D000804">Angiotensin II</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>6SMK8R7TGJ</RegistryNumber>
<NameOfSubstance UI="D009828">Oleanolic Acid</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>85637-73-6</RegistryNumber>
<NameOfSubstance UI="D009320">Atrial Natriuretic Factor</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>CEG1Q6OGU1</RegistryNumber>
<NameOfSubstance UI="C445068">methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 1.14.13.39</RegistryNumber>
<NameOfSubstance UI="D052250">Nitric Oxide Synthase Type III</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 1.14.13.39</RegistryNumber>
<NameOfSubstance UI="C496316">Nos3 protein, rat</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000804" MajorTopicYN="N">Angiotensin II</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009320" MajorTopicYN="N">Atrial Natriuretic Factor</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005353" MajorTopicYN="N">Fibronectins</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054477" MajorTopicYN="N">Glutaredoxins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006321" MajorTopicYN="N">Heart</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
<QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009203" MajorTopicYN="N">Myocardial Infarction</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051267" MajorTopicYN="N">NF-E2-Related Factor 2</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D052250" MajorTopicYN="N">Nitric Oxide Synthase Type III</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009828" MajorTopicYN="N">Oleanolic Acid</DescriptorName>
<QualifierName UI="Q000031" MajorTopicYN="Y">analogs & derivatives</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D010084" MajorTopicYN="N">Oxidation-Reduction</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D034741" MajorTopicYN="N">RNA, Small Interfering</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D020257" MajorTopicYN="N">Ventricular Remodeling</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Bardoxolone</Keyword>
<Keyword MajorTopicYN="Y">Caveolae</Keyword>
<Keyword MajorTopicYN="Y">Endothelial nitric oxide synthase</Keyword>
<Keyword MajorTopicYN="Y">Glutaredoxin</Keyword>
<Keyword MajorTopicYN="Y">Heart failure</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year>
<Month>07</Month>
<Day>21</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2017</Year>
<Month>03</Month>
<Day>24</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2017</Year>
<Month>04</Month>
<Day>19</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2017</Year>
<Month>4</Month>
<Day>26</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2018</Year>
<Month>4</Month>
<Day>10</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2017</Year>
<Month>4</Month>
<Day>26</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">28438659</ArticleId>
<ArticleId IdType="pii">S0891-5849(17)30230-7</ArticleId>
<ArticleId IdType="doi">10.1016/j.freeradbiomed.2017.04.027</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>Australie</li>
<li>Norvège</li>
<li>États-Unis</li>
</country>
<region><li>Nouvelle-Galles du Sud</li>
<li>Texas</li>
<li>Victoria (État)</li>
</region>
<settlement><li>Melbourne</li>
<li>Sydney</li>
</settlement>
<orgName><li>Université de Sydney</li>
</orgName>
</list>
<tree><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Bubb, Kristen J" sort="Bubb, Kristen J" uniqKey="Bubb K" first="Kristen J" last="Bubb">Kristen J. Bubb</name>
</region>
<name sortKey="Bhindi, Ravinay" sort="Bhindi, Ravinay" uniqKey="Bhindi R" first="Ravinay" last="Bhindi">Ravinay Bhindi</name>
<name sortKey="Figtree, Gemma A" sort="Figtree, Gemma A" uniqKey="Figtree G" first="Gemma A" last="Figtree">Gemma A. Figtree</name>
<name sortKey="Hansen, Thomas" sort="Hansen, Thomas" uniqKey="Hansen T" first="Thomas" last="Hansen">Thomas Hansen</name>
<name sortKey="Karimi Galougahi, Keyvan" sort="Karimi Galougahi, Keyvan" uniqKey="Karimi Galougahi K" first="Keyvan" last="Karimi Galougahi">Keyvan Karimi Galougahi</name>
<name sortKey="Kok, Cindy" sort="Kok, Cindy" uniqKey="Kok C" first="Cindy" last="Kok">Cindy Kok</name>
<name sortKey="Rasko, Nathalie B" sort="Rasko, Nathalie B" uniqKey="Rasko N" first="Nathalie B" last="Rasko">Nathalie B. Rasko</name>
<name sortKey="Ritchie, Rebecca" sort="Ritchie, Rebecca" uniqKey="Ritchie R" first="Rebecca" last="Ritchie">Rebecca Ritchie</name>
<name sortKey="Tang, Owen" sort="Tang, Owen" uniqKey="Tang O" first="Owen" last="Tang">Owen Tang</name>
</country>
<country name="Norvège"><noRegion><name sortKey="Birgisdottir, Asa B" sort="Birgisdottir, Asa B" uniqKey="Birgisdottir A" first="Asa B" last="Birgisdottir">Asa B. Birgisdottir</name>
</noRegion>
</country>
<country name="États-Unis"><region name="Texas"><name sortKey="Reisman, Scott A" sort="Reisman, Scott A" uniqKey="Reisman S" first="Scott A" last="Reisman">Scott A. Reisman</name>
</region>
<name sortKey="Meyer, Colin" sort="Meyer, Colin" uniqKey="Meyer C" first="Colin" last="Meyer">Colin Meyer</name>
<name sortKey="Ward, Keith" sort="Ward, Keith" uniqKey="Ward K" first="Keith" last="Ward">Keith Ward</name>
</country>
</tree>
</affiliations>
</record>

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The NRF2 activator DH404 attenuates adverse ventricular remodeling post-myocardial infarction by modifying redox signalling.

The NRF2 activator DH404 attenuates adverse ventricular remodeling post-myocardial infarction by modifying redox signalling.

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