mTOR-Notch3 signaling mediates pulmonary hypertension in hypoxia-exposed neonatal rats independent of changes in autophagy.
Identifieur interne : 000398 ( Ncbi/Merge ); précédent : 000397; suivant : 000399mTOR-Notch3 signaling mediates pulmonary hypertension in hypoxia-exposed neonatal rats independent of changes in autophagy.
Auteurs : Julijana Ivanovska [Canada] ; Sparsh Shah [Canada] ; Mathew J. Wong [Canada] ; Crystal Kantores [Canada] ; Amish Jain [Canada] ; Martin Post [Canada] ; Behzad Yeganeh [Canada] ; Robert P. Jankov [Canada]Source :
- Pediatric pulmonology [ 1099-0496 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux, Animaux nouveau-nés, Artère pulmonaire (métabolisme), Autophagie, Diamines (pharmacologie), Femelle, Hypertension pulmonaire (métabolisme), Hypoxie (métabolisme), Myocytes du muscle lisse (métabolisme), Mâle, Poumon (), Poumon (métabolisme), Prolifération cellulaire (), Rat Sprague-Dawley, Récepteur Notch3 (antagonistes et inhibiteurs), Récepteur Notch3 (métabolisme), Récepteur au PDGF bêta (métabolisme), Sirolimus (analogues et dérivés), Sirolimus (pharmacologie), Sérine-thréonine kinases TOR (antagonistes et inhibiteurs), Sérine-thréonine kinases TOR (métabolisme), Thiazoles (pharmacologie), Transduction du signal.
- MESH :
- analogues et dérivés : Sirolimus.
- antagonistes et inhibiteurs : Récepteur Notch3, Sérine-thréonine kinases TOR.
- métabolisme : Artère pulmonaire, Hypertension pulmonaire, Hypoxie, Myocytes du muscle lisse, Poumon, Récepteur Notch3, Récepteur au PDGF bêta, Sérine-thréonine kinases TOR.
- pharmacologie : Diamines, Sirolimus, Thiazoles.
- Animaux, Animaux nouveau-nés, Autophagie, Femelle, Mâle, Poumon, Prolifération cellulaire, Rat Sprague-Dawley, Transduction du signal.
English descriptors
- KwdEn :
- Animals, Animals, Newborn, Autophagy, Cell Proliferation (drug effects), Diamines (pharmacology), Female, Hypertension, Pulmonary (metabolism), Hypoxia (metabolism), Lung (blood supply), Lung (metabolism), Male, Myocytes, Smooth Muscle (metabolism), Pulmonary Artery (metabolism), Rats, Sprague-Dawley, Receptor, Notch3 (antagonists & inhibitors), Receptor, Notch3 (metabolism), Receptor, Platelet-Derived Growth Factor beta (metabolism), Signal Transduction, Sirolimus (analogs & derivatives), Sirolimus (pharmacology), TOR Serine-Threonine Kinases (antagonists & inhibitors), TOR Serine-Threonine Kinases (metabolism), Thiazoles (pharmacology).
- MESH :
- chemical , analogs & derivatives : Sirolimus.
- chemical , antagonists & inhibitors : Receptor, Notch3, TOR Serine-Threonine Kinases.
- chemical , metabolism : Receptor, Notch3, Receptor, Platelet-Derived Growth Factor beta, TOR Serine-Threonine Kinases.
- chemical , pharmacology : Diamines, Sirolimus, Thiazoles.
- blood supply : Lung.
- drug effects : Cell Proliferation.
- metabolism : Hypertension, Pulmonary, Hypoxia, Lung, Myocytes, Smooth Muscle, Pulmonary Artery.
- Animals, Animals, Newborn, Autophagy, Female, Male, Rats, Sprague-Dawley, Signal Transduction.
Abstract
Mammalian target of rapamycin (mTOR) is a pivotal regulator of cell proliferation, survival, and autophagy. Autophagy is increased in adult experimental chronic pulmonary hypertension (PHT), but its contributory role to pulmonary vascular disease remains uncertain and has yet to be explored in the neonatal animal. Notch is a major pro-proliferative pathway activated by mTOR. A direct relationship between autophagy and Notch signaling has not been previously explored. Our aim was to examine changes in mTOR-, Notch-, and autophagy-related pathways and the therapeutic effects of autophagy modulators in experimental chronic neonatal PHT secondary to chronic hypoxia.
DOI: 10.1002/ppul.23777
PubMed: 28759157
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pubmed:28759157Le document en format XML
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Wong</name><affiliation wicri:level="1"><nlm:affiliation>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Kantores, Crystal" sort="Kantores, Crystal" uniqKey="Kantores C" first="Crystal" last="Kantores">Crystal Kantores</name><affiliation wicri:level="1"><nlm:affiliation>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Jain, Amish" sort="Jain, Amish" uniqKey="Jain A" first="Amish" last="Jain">Amish Jain</name><affiliation wicri:level="1"><nlm:affiliation>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Post, Martin" sort="Post, Martin" uniqKey="Post M" first="Martin" last="Post">Martin Post</name><affiliation wicri:level="1"><nlm:affiliation>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Yeganeh, Behzad" sort="Yeganeh, Behzad" uniqKey="Yeganeh B" first="Behzad" last="Yeganeh">Behzad Yeganeh</name><affiliation wicri:level="1"><nlm:affiliation>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Jankov, Robert P" sort="Jankov, Robert P" uniqKey="Jankov R" first="Robert P" last="Jankov">Robert P. Jankov</name><affiliation wicri:level="1"><nlm:affiliation>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author></analytic><series><title level="j">Pediatric pulmonology</title><idno type="eISSN">1099-0496</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Animals, Newborn</term><term>Autophagy</term><term>Cell Proliferation (drug effects)</term><term>Diamines (pharmacology)</term><term>Female</term><term>Hypertension, Pulmonary (metabolism)</term><term>Hypoxia (metabolism)</term><term>Lung (blood supply)</term><term>Lung (metabolism)</term><term>Male</term><term>Myocytes, Smooth Muscle (metabolism)</term><term>Pulmonary Artery (metabolism)</term><term>Rats, Sprague-Dawley</term><term>Receptor, Notch3 (antagonists & inhibitors)</term><term>Receptor, Notch3 (metabolism)</term><term>Receptor, Platelet-Derived Growth Factor beta (metabolism)</term><term>Signal Transduction</term><term>Sirolimus (analogs & derivatives)</term><term>Sirolimus (pharmacology)</term><term>TOR Serine-Threonine Kinases (antagonists & inhibitors)</term><term>TOR Serine-Threonine Kinases (metabolism)</term><term>Thiazoles (pharmacology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Animaux nouveau-nés</term><term>Artère pulmonaire (métabolisme)</term><term>Autophagie</term><term>Diamines (pharmacologie)</term><term>Femelle</term><term>Hypertension pulmonaire (métabolisme)</term><term>Hypoxie (métabolisme)</term><term>Myocytes du muscle lisse (métabolisme)</term><term>Mâle</term><term>Poumon ()</term><term>Poumon (métabolisme)</term><term>Prolifération cellulaire ()</term><term>Rat Sprague-Dawley</term><term>Récepteur Notch3 (antagonistes et inhibiteurs)</term><term>Récepteur Notch3 (métabolisme)</term><term>Récepteur au PDGF bêta (métabolisme)</term><term>Sirolimus (analogues et dérivés)</term><term>Sirolimus (pharmacologie)</term><term>Sérine-thréonine kinases TOR (antagonistes et inhibiteurs)</term><term>Sérine-thréonine kinases TOR (métabolisme)</term><term>Thiazoles (pharmacologie)</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Sirolimus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Receptor, Notch3</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Receptor, Notch3</term><term>Receptor, Platelet-Derived Growth Factor beta</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Diamines</term><term>Sirolimus</term><term>Thiazoles</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Sirolimus</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Récepteur Notch3</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="blood supply" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Proliferation</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Hypertension, Pulmonary</term><term>Hypoxia</term><term>Lung</term><term>Myocytes, Smooth Muscle</term><term>Pulmonary Artery</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Artère pulmonaire</term><term>Hypertension pulmonaire</term><term>Hypoxie</term><term>Myocytes du muscle lisse</term><term>Poumon</term><term>Récepteur Notch3</term><term>Récepteur au PDGF bêta</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Diamines</term><term>Sirolimus</term><term>Thiazoles</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Animals, Newborn</term><term>Autophagy</term><term>Female</term><term>Male</term><term>Rats, Sprague-Dawley</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Animaux nouveau-nés</term><term>Autophagie</term><term>Femelle</term><term>Mâle</term><term>Poumon</term><term>Prolifération cellulaire</term><term>Rat Sprague-Dawley</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mammalian target of rapamycin (mTOR) is a pivotal regulator of cell proliferation, survival, and autophagy. Autophagy is increased in adult experimental chronic pulmonary hypertension (PHT), but its contributory role to pulmonary vascular disease remains uncertain and has yet to be explored in the neonatal animal. Notch is a major pro-proliferative pathway activated by mTOR. A direct relationship between autophagy and Notch signaling has not been previously explored. Our aim was to examine changes in mTOR-, Notch-, and autophagy-related pathways and the therapeutic effects of autophagy modulators in experimental chronic neonatal PHT secondary to chronic hypoxia.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" IndexingMethod="Curated" Owner="NLM"><PMID Version="1">28759157</PMID><DateCompleted><Year>2018</Year><Month>04</Month><Day>16</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>02</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1099-0496</ISSN><JournalIssue CitedMedium="Internet"><Volume>52</Volume><Issue>11</Issue><PubDate><Year>2017</Year><Month>Nov</Month></PubDate></JournalIssue><Title>Pediatric pulmonology</Title><ISOAbbreviation>Pediatr. Pulmonol.</ISOAbbreviation></Journal><ArticleTitle>mTOR-Notch3 signaling mediates pulmonary hypertension in hypoxia-exposed neonatal rats independent of changes in autophagy.</ArticleTitle><Pagination><MedlinePgn>1443-1454</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/ppul.23777</ELocationID><Abstract><AbstractText Label="BACKGROUND/AIM" NlmCategory="OBJECTIVE">Mammalian target of rapamycin (mTOR) is a pivotal regulator of cell proliferation, survival, and autophagy. Autophagy is increased in adult experimental chronic pulmonary hypertension (PHT), but its contributory role to pulmonary vascular disease remains uncertain and has yet to be explored in the neonatal animal. Notch is a major pro-proliferative pathway activated by mTOR. A direct relationship between autophagy and Notch signaling has not been previously explored. Our aim was to examine changes in mTOR-, Notch-, and autophagy-related pathways and the therapeutic effects of autophagy modulators in experimental chronic neonatal PHT secondary to chronic hypoxia.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Rat pups were exposed to normoxia or hypoxia (13% O<sub>2</sub> ) from postnatal days 1-21, while receiving treatment with temsirolimus (mTOR inhibitor), DAPT (Notch inhibitor), or chloroquine (inhibitor of autophagic flux).</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Exposure to hypoxia up-regulated autophagy and Notch3 signaling markers in lung, pulmonary artery (PA), and PA-derived smooth muscle cells (SMCs). Temsirolimus prevented chronic PHT and attenuated PA and SMC signaling secondary to hypoxia. These effects were replicated by DAPT. mTOR or Notch inhibition also down-regulated smooth muscle content of platelet-derived growth factor β-receptor, a known contributor to vascular remodeling. In contrast, chloroquine had no modifying effects on markers of chronic PHT. Knockdown of Beclin-1 in SMCs had no effect on hypoxia-stimulated Notch3 signaling.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">mTOR-Notch3 signaling plays a critical role in experimental chronic neonatal PHT. Inhibition of autophagy did not suppress Notch signaling and had no effect on markers of chronic PHT.</AbstractText><CopyrightInformation>© 2017 Wiley Periodicals, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ivanovska</LastName><ForeName>Julijana</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shah</LastName><ForeName>Sparsh</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wong</LastName><ForeName>Mathew J</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Faculty of Medicine, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kantores</LastName><ForeName>Crystal</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jain</LastName><ForeName>Amish</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Faculty of Medicine, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Faculty of Medicine, Department of Physiology, University of Toronto, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Post</LastName><ForeName>Martin</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Faculty of Medicine, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Faculty of Medicine, Department of Physiology, University of Toronto, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yeganeh</LastName><ForeName>Behzad</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jankov</LastName><ForeName>Robert P</ForeName><Initials>RP</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-9095-4398</Identifier><AffiliationInfo><Affiliation>Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Faculty of Medicine, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Faculty of Medicine, Department of Physiology, University of Toronto, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Molecular Biomedicine Program, Children's Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, Ontario, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Faculty of Medicine, Department of Paediatrics, University of Ottawa, Ottawa, Ontario, Canada.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>07</Month><Day>31</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Pediatr Pulmonol</MedlineTA><NlmUniqueID>8510590</NlmUniqueID><ISSNLinking>1099-0496</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C000612000">24-diamino-5-phenylthiazole</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D003959">Diamines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C498556">Notch3 protein, rat</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000071656">Receptor, Notch3</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013844">Thiazoles</NameOfSubstance></Chemical><Chemical><RegistryNumber>624KN6GM2T</RegistryNumber><NameOfSubstance UI="C401859">temsirolimus</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="C546845">mTOR protein, rat</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance UI="D020797">Receptor, Platelet-Derived Growth Factor beta</NameOfSubstance></Chemical><Chemical><RegistryNumber>W36ZG6FT64</RegistryNumber><NameOfSubstance UI="D020123">Sirolimus</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000831" MajorTopicYN="N">Animals, Newborn</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003959" MajorTopicYN="N">Diamines</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006976" MajorTopicYN="N">Hypertension, Pulmonary</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000860" MajorTopicYN="N">Hypoxia</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008168" MajorTopicYN="N">Lung</DescriptorName><QualifierName UI="Q000098" MajorTopicYN="N">blood supply</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D032389" MajorTopicYN="N">Myocytes, Smooth Muscle</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011651" MajorTopicYN="N">Pulmonary Artery</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000071656" MajorTopicYN="N">Receptor, Notch3</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020797" MajorTopicYN="N">Receptor, Platelet-Derived Growth Factor beta</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020123" MajorTopicYN="N">Sirolimus</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="N">analogs & derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013844" MajorTopicYN="N">Thiazoles</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">neonatal pulmonary medicine</Keyword><Keyword MajorTopicYN="N">pulmonary hypertension</Keyword><Keyword MajorTopicYN="N">pulmonary vascular disorders</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year><Month>03</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017</Year><Month>07</Month><Day>06</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>8</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>4</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>8</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28759157</ArticleId><ArticleId IdType="doi">10.1002/ppul.23777</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Ivanovska, Julijana" sort="Ivanovska, Julijana" uniqKey="Ivanovska J" first="Julijana" last="Ivanovska">Julijana Ivanovska</name></noRegion><name sortKey="Jain, Amish" sort="Jain, Amish" uniqKey="Jain A" first="Amish" last="Jain">Amish Jain</name><name sortKey="Jankov, Robert P" sort="Jankov, Robert P" uniqKey="Jankov R" first="Robert P" last="Jankov">Robert P. Jankov</name><name sortKey="Kantores, Crystal" sort="Kantores, Crystal" uniqKey="Kantores C" first="Crystal" last="Kantores">Crystal Kantores</name><name sortKey="Post, Martin" sort="Post, Martin" uniqKey="Post M" first="Martin" last="Post">Martin Post</name><name sortKey="Shah, Sparsh" sort="Shah, Sparsh" uniqKey="Shah S" first="Sparsh" last="Shah">Sparsh Shah</name><name sortKey="Wong, Mathew J" sort="Wong, Mathew J" uniqKey="Wong M" first="Mathew J" last="Wong">Mathew J. Wong</name><name sortKey="Yeganeh, Behzad" sort="Yeganeh, Behzad" uniqKey="Yeganeh B" first="Behzad" last="Yeganeh">Behzad Yeganeh</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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