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Treprostinil increases the number and angiogenic potential of endothelial progenitor cells in children with pulmonary hypertension

Identifieur interne : 002447 ( Pmc/Checkpoint ); précédent : 002446; suivant : 002448

Treprostinil increases the number and angiogenic potential of endothelial progenitor cells in children with pulmonary hypertension

Auteurs : David M. Smadja [France, États-Unis] ; Laetitia Mauge [France] ; Pascale Gaussem [France] ; Clément D Udigier [France] ; Dominique Israel-Biet [France] ; David S. Celermajer [Australie] ; Damien Bonnet [France] ; Marilyne Lévy [France]

Source :

RBID : PMC:3040815

Abstract

Background

Pulmonary vasodilators in general and prostacyclin therapy in particular, have markedly improved the outcome of patients with pulmonary arterial hypertension (PAH). As endothelial dysfunction is a key feature of PAH, and as endothelial progenitor cells (EPC) may contribute to vascular repair in PAH, we suspected that prostacyclin therapy might enhance EPC numbers and functions. In the present study, objectives were to determine whether EPC may contribute to vasodilator treatment efficacy in PAH.

Methods

We quantified CD34+ cells, CFU-Hill and ECFC (endothelial colony forming cells) in peripheral blood from children with idiopathic PAH (n = 27) or PAH secondary to congenital heart disease (n = 52). CD34+ were enumerated by flow cytometry, CFU-Hill and ECFC by a culture assay. ECFC grown ex vivo were tested for their angiogenic capacities before and after prostacyclin analog therapy (subcutaneous treprostinil).

Results

ECFC counts were significantly enhanced in the 8 children treated with treprostinil, while no change was observed in children receiving oral therapy with endothelin antagonists and/or PDE5 inhibitors. CD34+ cell and CFU-Hill counts were unaffected. ECFC from patients treated with treprostinil had a hyperproliferative phenotype and showed enhanced angiogenic potential in a nude mouse preclinical model of limb ischemia.

Conclusions

ECFC may partly mediate the clinical benefits of prostanoids in pulmonary arterial hypertension.


Url:
DOI: 10.1007/s10456-010-9192-y
PubMed: 21049284
PubMed Central: 3040815


Affiliations:


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PMC:3040815

Le document en format XML

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<name sortKey="Celermajer, David S" sort="Celermajer, David S" uniqKey="Celermajer D" first="David S." last="Celermajer">David S. Celermajer</name>
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<name sortKey="Bonnet, Damien" sort="Bonnet, Damien" uniqKey="Bonnet D" first="Damien" last="Bonnet">Damien Bonnet</name>
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<affiliation wicri:level="4">
<nlm:aff id="Aff1">Université Paris Descartes, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Paris Descartes, 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="Aff5">UPRES EA4068, UFR Biomédicale des Saints Pères, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>UPRES EA4068, UFR Biomédicale des Saints Pères, 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="Aff7">AP-HP, Hôpital Necker-Enfants Malades, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>AP-HP, Hôpital Necker-Enfants Malades, 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">Angiogenesis</title>
<idno type="ISSN">0969-6970</idno>
<idno type="eISSN">1573-7209</idno>
<imprint>
<date when="2010">2010</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 therapy in particular, have markedly improved the outcome of patients with pulmonary arterial hypertension (PAH). As endothelial dysfunction is a key feature of PAH, and as endothelial progenitor cells (EPC) may contribute to vascular repair in PAH, we suspected that prostacyclin therapy might enhance EPC numbers and functions. In the present study, objectives were to determine whether EPC may contribute to vasodilator treatment efficacy in PAH.</p>
</sec>
<sec>
<title>Methods</title>
<p>We quantified CD34+ cells, CFU-Hill and ECFC (endothelial colony forming cells) in peripheral blood from children with idiopathic PAH (
<italic>n</italic>
 = 27) or PAH secondary to congenital heart disease (
<italic>n</italic>
 = 52). CD34+ were enumerated by flow cytometry, CFU-Hill and ECFC by a culture assay. ECFC grown ex vivo were tested for their angiogenic capacities before and after prostacyclin analog therapy (subcutaneous treprostinil).</p>
</sec>
<sec>
<title>Results</title>
<p>ECFC counts were significantly enhanced in the 8 children treated with treprostinil, while no change was observed in children receiving oral therapy with endothelin antagonists and/or PDE5 inhibitors. CD34+ cell and CFU-Hill counts were unaffected. ECFC from patients treated with treprostinil had a hyperproliferative phenotype and showed enhanced angiogenic potential in a nude mouse preclinical model of limb ischemia.</p>
</sec>
<sec>
<title>Conclusions</title>
<p>ECFC may partly mediate the clinical benefits of prostanoids in pulmonary arterial hypertension.</p>
</sec>
</div>
</front>
<back>
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</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Angiogenesis</journal-id>
<journal-title-group>
<journal-title>Angiogenesis</journal-title>
</journal-title-group>
<issn pub-type="ppub">0969-6970</issn>
<issn pub-type="epub">1573-7209</issn>
<publisher>
<publisher-name>Springer Netherlands</publisher-name>
<publisher-loc>Dordrecht</publisher-loc>
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</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">21049284</article-id>
<article-id pub-id-type="pmc">3040815</article-id>
<article-id pub-id-type="publisher-id">9192</article-id>
<article-id pub-id-type="doi">10.1007/s10456-010-9192-y</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Paper</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Treprostinil increases the number and angiogenic potential of endothelial progenitor cells in children with pulmonary hypertension</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Smadja</surname>
<given-names>David M.</given-names>
</name>
<address>
<phone>+33-1-56093933</phone>
<fax>+33-1-56093393</fax>
<email>david.smadja@egp.aphp.fr</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff4">4</xref>
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<contrib contrib-type="author">
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<surname>Mauge</surname>
<given-names>Laetitia</given-names>
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<xref ref-type="aff" rid="Aff1">1</xref>
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<contrib contrib-type="author">
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<surname>Gaussem</surname>
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<contrib contrib-type="author">
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<surname>d’Audigier</surname>
<given-names>Clément</given-names>
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<contrib contrib-type="author">
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<surname>Israel-Biet</surname>
<given-names>Dominique</given-names>
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<contrib contrib-type="author">
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<surname>Celermajer</surname>
<given-names>David S.</given-names>
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<xref ref-type="aff" rid="Aff5">5</xref>
<xref ref-type="aff" rid="Aff7">7</xref>
</contrib>
<aff id="Aff1">
<label>1</label>
Université Paris Descartes, Paris, France</aff>
<aff id="Aff2">
<label>2</label>
Inserm Unité 765, Faculté de Pharmacie, and AP-HP, Hôpital Européen Georges Pompidou, Haematology Department, 20 rue leblanc, 75015 Paris, France</aff>
<aff id="Aff3">
<label>3</label>
AP-HP, Hôpital Européen Georges Pompidou, Pneumology Department, Paris, France</aff>
<aff id="Aff4">
<label>4</label>
Vascular Biology Program, Children’s Hospital, Harvard Medical School, Boston, MA USA</aff>
<aff id="Aff5">
<label>5</label>
UPRES EA4068, UFR Biomédicale des Saints Pères, Paris, France</aff>
<aff id="Aff6">
<label>6</label>
Sydney Medical School, University of Sydney, Sydney, NSW 2006 Australia</aff>
<aff id="Aff7">
<label>7</label>
AP-HP, Hôpital Necker-Enfants Malades, Paris, France</aff>
</contrib-group>
<pub-date pub-type="epub">
<day>4</day>
<month>11</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>4</day>
<month>11</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="ppub">
<month>3</month>
<year>2011</year>
</pub-date>
<volume>14</volume>
<issue>1</issue>
<fpage>17</fpage>
<lpage>27</lpage>
<history>
<date date-type="received">
<day>10</day>
<month>9</month>
<year>2010</year>
</date>
<date date-type="accepted">
<day>19</day>
<month>10</month>
<year>2010</year>
</date>
</history>
<permissions>
<copyright-statement>© The Author(s) 2010</copyright-statement>
</permissions>
<abstract id="Abs1">
<sec>
<title>Background</title>
<p>Pulmonary vasodilators in general and prostacyclin therapy in particular, have markedly improved the outcome of patients with pulmonary arterial hypertension (PAH). As endothelial dysfunction is a key feature of PAH, and as endothelial progenitor cells (EPC) may contribute to vascular repair in PAH, we suspected that prostacyclin therapy might enhance EPC numbers and functions. In the present study, objectives were to determine whether EPC may contribute to vasodilator treatment efficacy in PAH.</p>
</sec>
<sec>
<title>Methods</title>
<p>We quantified CD34+ cells, CFU-Hill and ECFC (endothelial colony forming cells) in peripheral blood from children with idiopathic PAH (
<italic>n</italic>
 = 27) or PAH secondary to congenital heart disease (
<italic>n</italic>
 = 52). CD34+ were enumerated by flow cytometry, CFU-Hill and ECFC by a culture assay. ECFC grown ex vivo were tested for their angiogenic capacities before and after prostacyclin analog therapy (subcutaneous treprostinil).</p>
</sec>
<sec>
<title>Results</title>
<p>ECFC counts were significantly enhanced in the 8 children treated with treprostinil, while no change was observed in children receiving oral therapy with endothelin antagonists and/or PDE5 inhibitors. CD34+ cell and CFU-Hill counts were unaffected. ECFC from patients treated with treprostinil had a hyperproliferative phenotype and showed enhanced angiogenic potential in a nude mouse preclinical model of limb ischemia.</p>
</sec>
<sec>
<title>Conclusions</title>
<p>ECFC may partly mediate the clinical benefits of prostanoids in pulmonary arterial hypertension.</p>
</sec>
</abstract>
<kwd-group>
<title>Keywords</title>
<kwd>Pulmonary hypertension</kwd>
<kwd>Congenital heart disease</kwd>
<kwd>Vasodilator treatment</kwd>
<kwd>Treprostinil</kwd>
<kwd>EPC</kwd>
</kwd-group>
<custom-meta-group>
<custom-meta>
<meta-name>issue-copyright-statement</meta-name>
<meta-value>© Springer Science+Business Media B.V. 2011</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations>
<list>
<country>
<li>Australie</li>
<li>France</li>
<li>États-Unis</li>
</country>
<region>
<li>Massachusetts</li>
<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="Smadja, David M" sort="Smadja, David M" uniqKey="Smadja D" first="David M." last="Smadja">David M. Smadja</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="D Udigier, Clement" sort="D Udigier, Clement" uniqKey="D Udigier C" first="Clément" last="D Udigier">Clément D Udigier</name>
<name sortKey="D Udigier, Clement" sort="D Udigier, Clement" uniqKey="D Udigier C" first="Clément" last="D Udigier">Clément D Udigier</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="Israel Biet, Dominique" sort="Israel Biet, Dominique" uniqKey="Israel Biet D" first="Dominique" last="Israel-Biet">Dominique Israel-Biet</name>
<name sortKey="Israel Biet, Dominique" sort="Israel Biet, Dominique" uniqKey="Israel Biet D" first="Dominique" last="Israel-Biet">Dominique Israel-Biet</name>
<name sortKey="Israel Biet, Dominique" sort="Israel Biet, Dominique" uniqKey="Israel Biet D" first="Dominique" last="Israel-Biet">Dominique Israel-Biet</name>
<name sortKey="Levy, Marilyne" sort="Levy, Marilyne" uniqKey="Levy M" first="Marilyne" last="Lévy">Marilyne Lévy</name>
<name sortKey="Levy, Marilyne" sort="Levy, Marilyne" uniqKey="Levy M" first="Marilyne" last="Lévy">Marilyne Lévy</name>
<name sortKey="Levy, Marilyne" sort="Levy, Marilyne" uniqKey="Levy M" first="Marilyne" last="Lévy">Marilyne Lévy</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>
</country>
<country name="États-Unis">
<region name="Massachusetts">
<name sortKey="Smadja, David M" sort="Smadja, David M" uniqKey="Smadja D" first="David M." last="Smadja">David M. Smadja</name>
</region>
</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>

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