Circulating Endothelial Cells in Refractory Pulmonary Hypertension in Children: Markers of Treatment Efficacy and Clinical Worsening
Identifieur interne : 001C12 ( Pmc/Checkpoint ); précédent : 001C11; suivant : 001C13Circulating Endothelial Cells in Refractory Pulmonary Hypertension in Children: Markers of Treatment Efficacy and Clinical Worsening
Auteurs : Marilyne Levy [France] ; Damien Bonnet [France] ; Laetitia Mauge [France] ; David S. Celermajer [Australie] ; Pascale Gaussem [France] ; David M. Smadja [France]Source :
- PLoS ONE [ 1932-6203 ] ; 2013.
Abstract
Pulmonary vasodilators in general and prostacyclin analogues in particular have improved the outcome of patients with pulmonary arterial hypertension (PAH). Endothelial dysfunction is a key feature of PAH and we previously described that circulating endothelial cell (CEC) level could be used as a biomarker of endothelial dysfunction in PAH. We now hypothesized that an efficient PAH-specific vasodilator therapy might decrease CEC level.
CECs were prospectively quantified by immunomagnetic separation with mAb CD146-coated beads in peripheral blood from children with idiopathic PAH (iPAH, n = 30) or PAH secondary to congenital heart disease (PAH-CHD, n = 30): before, after treatment and during follow up. Controls were 23 children with reversible PAH. Oral treatment with endothelin receptor antagonists (ERA) and/or phosphodiesterase 5 inhibitors (PDE5) significantly reduced CEC counts in children. In 10 children with refractory PAH despite oral combination therapy, subcutaneous (SC) treprostinil was added and we observed a significant decrease in CEC counts during the first month of such treatment. CECs were quantified during a 6 to 36 month-follow-up after initiation of SC treprostinil and we found that CEC counts changed over time, with rising counts always preceding clinical deterioration.
CECs might be useful as a biomarker during follow-up of pediatric iPAH and PAH-CHD to assess response to treatment and to anticipate clinical worsening.
Url:
DOI: 10.1371/journal.pone.0065114
PubMed: 23762293
PubMed Central: 3677895
Affiliations:
- Australie, France
- Nouvelle-Galles du Sud, Île-de-France
- Paris, Sydney
- Université Paris-Descartes, Université de Sydney
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region">Île-de-France</region><settlement type="city">Paris</settlement><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>AP-HP, Hôpital Necker-Enfants Malades, Centre de Référence Malformations Cardiaques Congénitales Complexes (M3C), Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>AP-HP, Hôpital Necker-Enfants Malades, Centre de Référence Malformations Cardiaques Congénitales Complexes (M3C), Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Bonnet, Damien" sort="Bonnet, Damien" uniqKey="Bonnet D" first="Damien" last="Bonnet">Damien Bonnet</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Université Paris 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type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Mauge, Laetitia" sort="Mauge, Laetitia" uniqKey="Mauge L" first="Laetitia" last="Mauge">Laetitia Mauge</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Université Paris Descartes, Sorbonne Paris Cité, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Descartes, Sorbonne Paris Cité, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Inserm UMR-S765, Faculté de Pharmacie, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S765, Faculté de Pharmacie, 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Celermajer</name><affiliation wicri:level="4"><nlm:aff id="aff5"><addr-line>Sydney Medical Schools, University of Sydney, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sydney Medical Schools, University of Sydney, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Gaussem, Pascale" sort="Gaussem, Pascale" uniqKey="Gaussem P" first="Pascale" last="Gaussem">Pascale Gaussem</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Université Paris Descartes, Sorbonne Paris Cité, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Descartes, Sorbonne Paris Cité, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Inserm UMR-S765, Faculté de Pharmacie, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S765, Faculté de Pharmacie, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff4"><addr-line>AP-HP, Hôpital Européen Georges Pompidou, Service d’hématologie Biologique, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>AP-HP, Hôpital Européen Georges Pompidou, Service d’hématologie Biologique, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Smadja, David M" sort="Smadja, David M" uniqKey="Smadja D" first="David M." last="Smadja">David M. Smadja</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Université Paris Descartes, Sorbonne Paris Cité, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Descartes, Sorbonne Paris Cité, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Inserm UMR-S765, Faculté de Pharmacie, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm UMR-S765, Faculté de Pharmacie, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff4"><addr-line>AP-HP, Hôpital Européen Georges Pompidou, Service d’hématologie Biologique, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>AP-HP, Hôpital Européen Georges Pompidou, Service d’hématologie Biologique, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Pulmonary vasodilators in general and prostacyclin analogues in particular have improved the outcome of patients with pulmonary arterial hypertension (PAH). Endothelial dysfunction is a key feature of PAH and we previously described that circulating endothelial cell (CEC) level could be used as a biomarker of endothelial dysfunction in PAH. We now hypothesized that an efficient PAH-specific vasodilator therapy might decrease CEC level.</p></sec><sec><title>Methods/Results</title><p>CECs were prospectively quantified by immunomagnetic separation with mAb CD146-coated beads in peripheral blood from children with idiopathic PAH (iPAH, n = 30) or PAH secondary to congenital heart disease (PAH-CHD, n = 30): before, after treatment and during follow up. Controls were 23 children with reversible PAH. Oral treatment with endothelin receptor antagonists (ERA) and/or phosphodiesterase 5 inhibitors (PDE5) significantly reduced CEC counts in children. In 10 children with refractory PAH despite oral combination therapy, subcutaneous (SC) treprostinil was added and we observed a significant decrease in CEC counts during the first month of such treatment. CECs were quantified during a 6 to 36 month-follow-up after initiation of SC treprostinil and we found that CEC counts changed over time, with rising counts always preceding clinical deterioration.</p></sec><sec><title>Conclusion</title><p>CECs might be useful as a biomarker during follow-up of pediatric iPAH and PAH-CHD to assess response to treatment and to anticipate clinical worsening.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Simonneau, G" uniqKey="Simonneau G">G Simonneau</name></author><author><name sortKey="Robbins, Im" uniqKey="Robbins I">IM Robbins</name></author><author><name sortKey="Beghetti, M" uniqKey="Beghetti M">M Beghetti</name></author><author><name sortKey="Channick, Rn" uniqKey="Channick R">RN Channick</name></author><author><name sortKey="Delcroix, M" uniqKey="Delcroix M">M Delcroix</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Galie, N" uniqKey="Galie N">N Galie</name></author><author><name sortKey="Hoeper, Mm" uniqKey="Hoeper M">MM Hoeper</name></author><author><name sortKey="Humbert, M" uniqKey="Humbert M">M Humbert</name></author><author><name sortKey="Torbicki, A" uniqKey="Torbicki A">A Torbicki</name></author><author><name sortKey="Vachiery, Jl" uniqKey="Vachiery J">JL Vachiery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Berger, Rm" uniqKey="Berger R">RM Berger</name></author><author><name sortKey="Bonnet, D" uniqKey="Bonnet D">D Bonnet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Callaghan, Ds" uniqKey="O Callaghan D">DS O'Callaghan</name></author><author><name sortKey="Savale, L" uniqKey="Savale L">L Savale</name></author><author><name sortKey="Jais, X" uniqKey="Jais X">X Jais</name></author><author><name sortKey="Natali, D" uniqKey="Natali D">D Natali</name></author><author><name sortKey="Montani, D" uniqKey="Montani D">D 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23762293</article-id><article-id pub-id-type="pmc">3677895</article-id><article-id pub-id-type="publisher-id">PONE-D-13-06642</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0065114</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject><subj-group><subject>Cardiovascular</subject><subj-group><subject>Cardiovascular Pharmacology</subject><subject>Heart Failure</subject><subject>Interventional Cardiology</subject><subject>Pediatric Cardiology</subject><subject>Pulmonary Vascular Diseases</subject></subj-group></subj-group><subj-group><subject>Diagnostic Medicine</subject><subj-group><subject>Pathology</subject><subj-group><subject>General Pathology</subject><subj-group><subject>Biomarkers</subject></subj-group></subj-group></subj-group></subj-group><subj-group><subject>Drugs and Devices</subject><subj-group><subject>Cardiovascular Pharmacology</subject></subj-group></subj-group><subj-group><subject>Hematology</subject></subj-group><subj-group><subject>Pediatrics</subject><subj-group><subject>Pediatric Cardiology</subject></subj-group></subj-group><subj-group><subject>Public Health</subject><subj-group><subject>Child Health</subject></subj-group></subj-group><subj-group><subject>Pulmonology</subject></subj-group></subj-group></article-categories><title-group><article-title>Circulating Endothelial Cells in Refractory Pulmonary Hypertension in Children: Markers of Treatment Efficacy and Clinical Worsening</article-title><alt-title alt-title-type="running-head">CEC in Pediatric Refractory Pulmonary Hypertension</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Levy</surname><given-names>Marilyne</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bonnet</surname><given-names>Damien</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mauge</surname><given-names>Laetitia</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Celermajer</surname><given-names>David S.</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gaussem</surname><given-names>Pascale</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Smadja</surname><given-names>David M.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Université Paris Descartes, Sorbonne Paris Cité, Paris, France</addr-line></aff><aff id="aff2"><label>2</label><addr-line>AP-HP, Hôpital Necker-Enfants Malades, Centre de Référence Malformations Cardiaques Congénitales Complexes (M3C), Paris, France</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Inserm UMR-S765, Faculté de Pharmacie, Paris, France</addr-line></aff><aff id="aff4"><label>4</label><addr-line>AP-HP, Hôpital Européen Georges Pompidou, Service d’hématologie Biologique, Paris, France</addr-line></aff><aff id="aff5"><label>5</label><addr-line>Sydney Medical Schools, University of Sydney, Sydney, Australia</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>West</surname><given-names>James</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>Vanderbilt University Medical Center, United States of America</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>david.smadja@egp.aphp.fr</email></corresp><fn fn-type="conflict"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: ML DMS. Performed the experiments: DMS LM. Analyzed the data: ML DMS. Contributed reagents/materials/analysis tools: ML DMS DB PG DSC. Wrote the paper: DMS.</p></fn></author-notes><pub-date pub-type="collection"><year>2013</year></pub-date><pub-date pub-type="epub"><day>10</day><month>6</month><year>2013</year></pub-date><volume>8</volume><issue>6</issue><elocation-id>e65114</elocation-id><history><date date-type="received"><day>11</day><month>2</month><year>2013</year></date><date date-type="accepted"><day>22</day><month>4</month><year>2013</year></date></history><permissions><copyright-year>2013</copyright-year><copyright-holder>Levy et al</copyright-holder><license><license-p>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.</license-p></license></permissions><abstract><sec><title>Background</title><p>Pulmonary vasodilators in general and prostacyclin analogues in particular have improved the outcome of patients with pulmonary arterial hypertension (PAH). Endothelial dysfunction is a key feature of PAH and we previously described that circulating endothelial cell (CEC) level could be used as a biomarker of endothelial dysfunction in PAH. We now hypothesized that an efficient PAH-specific vasodilator therapy might decrease CEC level.</p></sec><sec><title>Methods/Results</title><p>CECs were prospectively quantified by immunomagnetic separation with mAb CD146-coated beads in peripheral blood from children with idiopathic PAH (iPAH, n = 30) or PAH secondary to congenital heart disease (PAH-CHD, n = 30): before, after treatment and during follow up. Controls were 23 children with reversible PAH. Oral treatment with endothelin receptor antagonists (ERA) and/or phosphodiesterase 5 inhibitors (PDE5) significantly reduced CEC counts in children. In 10 children with refractory PAH despite oral combination therapy, subcutaneous (SC) treprostinil was added and we observed a significant decrease in CEC counts during the first month of such treatment. CECs were quantified during a 6 to 36 month-follow-up after initiation of SC treprostinil and we found that CEC counts changed over time, with rising counts always preceding clinical deterioration.</p></sec><sec><title>Conclusion</title><p>CECs might be useful as a biomarker during follow-up of pediatric iPAH and PAH-CHD to assess response to treatment and to anticipate clinical worsening.</p></sec></abstract><funding-group><funding-statement>This work was supported by research grants from INSERM, Leg Poix (Paris, France) andARCFA (Association pour la Recherche en Cardiologie du Foetus à l'Adulte). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="10"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Nouvelle-Galles du Sud</li><li>Île-de-France</li></region><settlement><li>Paris</li><li>Sydney</li></settlement><orgName><li>Université Paris-Descartes</li><li>Université de Sydney</li></orgName></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Levy, Marilyne" sort="Levy, Marilyne" uniqKey="Levy M" first="Marilyne" last="Levy">Marilyne Levy</name></region><name sortKey="Bonnet, Damien" sort="Bonnet, Damien" uniqKey="Bonnet D" first="Damien" last="Bonnet">Damien Bonnet</name><name sortKey="Bonnet, Damien" sort="Bonnet, Damien" uniqKey="Bonnet D" first="Damien" last="Bonnet">Damien Bonnet</name><name sortKey="Gaussem, Pascale" sort="Gaussem, Pascale" uniqKey="Gaussem P" first="Pascale" last="Gaussem">Pascale Gaussem</name><name sortKey="Gaussem, Pascale" sort="Gaussem, Pascale" uniqKey="Gaussem P" first="Pascale" last="Gaussem">Pascale Gaussem</name><name sortKey="Gaussem, Pascale" sort="Gaussem, Pascale" uniqKey="Gaussem P" first="Pascale" last="Gaussem">Pascale Gaussem</name><name sortKey="Levy, Marilyne" sort="Levy, Marilyne" uniqKey="Levy M" first="Marilyne" last="Levy">Marilyne Levy</name><name sortKey="Mauge, Laetitia" sort="Mauge, Laetitia" uniqKey="Mauge L" first="Laetitia" last="Mauge">Laetitia Mauge</name><name sortKey="Mauge, Laetitia" sort="Mauge, Laetitia" uniqKey="Mauge L" first="Laetitia" last="Mauge">Laetitia Mauge</name><name sortKey="Mauge, Laetitia" sort="Mauge, Laetitia" uniqKey="Mauge L" first="Laetitia" last="Mauge">Laetitia Mauge</name><name sortKey="Smadja, David M" sort="Smadja, David M" uniqKey="Smadja D" first="David M." last="Smadja">David M. Smadja</name><name sortKey="Smadja, David M" sort="Smadja, David M" uniqKey="Smadja D" first="David M." last="Smadja">David M. Smadja</name><name sortKey="Smadja, David M" sort="Smadja, David M" uniqKey="Smadja D" first="David M." last="Smadja">David M. Smadja</name></country><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Celermajer, David S" sort="Celermajer, David S" uniqKey="Celermajer D" first="David S." last="Celermajer">David S. Celermajer</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|flux= Pmc
|étape= Checkpoint
|type= RBID
|clé= PMC:3677895
|texte= Circulating Endothelial Cells in Refractory Pulmonary Hypertension in Children: Markers of Treatment Efficacy and Clinical Worsening
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/RBID.i -Sk "pubmed:23762293" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |