Circulating Endothelial Cells in Refractory Pulmonary Hypertension in Children: Markers of Treatment Efficacy and Clinical Worsening
Identifieur interne : 004795 ( Main/Exploration ); précédent : 004794; suivant : 004796Circulating 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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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 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="aff2"><addr-line>AP-HP, Hôpital Necker-Enfants Malades, Centre de Référence Malformations Cardiaques Congénitales Complexes (M3C), Paris, France</addr-line></nlm:aff><country 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type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Celermajer, David S" sort="Celermajer, David S" uniqKey="Celermajer D" first="David S." last="Celermajer">David S. 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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Warner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rizzo, No" uniqKey="Rizzo N">NO Rizzo</name></author><author><name sortKey="Maloney, E" uniqKey="Maloney E">E Maloney</name></author><author><name sortKey="Pham, M" uniqKey="Pham M">M Pham</name></author><author><name sortKey="Luttrell, I" uniqKey="Luttrell I">I Luttrell</name></author><author><name sortKey="Wessells, H" uniqKey="Wessells H">H Wessells</name></author></analytic></biblStruct></listBibl></div1></back></TEI><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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