Circulating endothelial cells in refractory pulmonary hypertension in children: markers of treatment efficacy and clinical worsening.
BACKGROUND: 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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3677895?pdf=render |
| _version_ | 1818851910842580992 |
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| author | Marilyne Levy Damien Bonnet Laetitia Mauge David S Celermajer Pascale Gaussem David M Smadja |
| author_facet | Marilyne Levy Damien Bonnet Laetitia Mauge David S Celermajer Pascale Gaussem David M Smadja |
| author_sort | Marilyne Levy |
| collection | DOAJ |
| description | BACKGROUND: 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. METHODS/RESULTS: 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. CONCLUSION: 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. |
| first_indexed | 2024-12-19T07:12:32Z |
| format | Article |
| id | doaj.art-77ec7cd2f31d4751a315a4d07a112d6d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T07:12:32Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-77ec7cd2f31d4751a315a4d07a112d6d2022-12-21T20:31:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6511410.1371/journal.pone.0065114Circulating endothelial cells in refractory pulmonary hypertension in children: markers of treatment efficacy and clinical worsening.Marilyne LevyDamien BonnetLaetitia MaugeDavid S CelermajerPascale GaussemDavid M SmadjaBACKGROUND: 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. METHODS/RESULTS: 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. CONCLUSION: 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.http://europepmc.org/articles/PMC3677895?pdf=render |
| spellingShingle | Marilyne Levy Damien Bonnet Laetitia Mauge David S Celermajer Pascale Gaussem David M Smadja Circulating endothelial cells in refractory pulmonary hypertension in children: markers of treatment efficacy and clinical worsening. PLoS ONE |
| title | Circulating endothelial cells in refractory pulmonary hypertension in children: markers of treatment efficacy and clinical worsening. |
| title_full | Circulating endothelial cells in refractory pulmonary hypertension in children: markers of treatment efficacy and clinical worsening. |
| title_fullStr | Circulating endothelial cells in refractory pulmonary hypertension in children: markers of treatment efficacy and clinical worsening. |
| title_full_unstemmed | Circulating endothelial cells in refractory pulmonary hypertension in children: markers of treatment efficacy and clinical worsening. |
| title_short | Circulating endothelial cells in refractory pulmonary hypertension in children: markers of treatment efficacy and clinical worsening. |
| title_sort | circulating endothelial cells in refractory pulmonary hypertension in children markers of treatment efficacy and clinical worsening |
| url | http://europepmc.org/articles/PMC3677895?pdf=render |
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