Thrombin Induces Angiotensin II-Mediated Senescence in Atrial Endothelial Cells: Impact on Pro-Remodeling Patterns
Identifieur interne : 000287 ( Pmc/Checkpoint ); précédent : 000286; suivant : 000288Thrombin Induces Angiotensin II-Mediated Senescence in Atrial Endothelial Cells: Impact on Pro-Remodeling Patterns
Auteurs : Hira Hasan [France] ; Sin-Hee Park [France] ; Cyril Auger [France] ; Eugenia Belcastro [France] ; Kensuke Matsushita [France] ; Benjamin Marchandot ; Hyun-Ho Lee [France] ; Abdul Wahid Qureshi [France] ; Gilles Kauffenstein [France] ; Patrick Ohlmann ; Valérie B. Schini-Kerth [France] ; Laurence Jesel [France] ; Olivier Morel [France]Source :
- Journal of Clinical Medicine [ 2077-0383 ] ; 2019.
Abstract
Background: Besides its well-known functions in hemostasis, thrombin plays a role in various non-hemostatic biological and pathophysiologic processes. We examined the potential of thrombin to promote premature atrial endothelial cells (ECs) senescence. Methods and Results: Primary ECs were isolated from porcine atrial tissue. Endothelial senescence was assessed by measuring beta-galactosidase (SA-β-gal) activity using flow cytometry, oxidative stress using the redox-sensitive probe dihydroethidium, protein level by Western blot, and matrix metalloproteinases (MMPs) activity using zymography. Atrial endothelial senescence was induced by thrombin at clinically relevant concentrations. Thrombin induced the up-regulation of p53, a key regulator in cellular senescence and of p21 and p16, two cyclin-dependent kinase inhibitors. Nicotinamide adenine dinucleotide phosphate NADPH oxidase, cyclooxygenases and the mitochondrial respiration complex contributed to oxidative stress and senescence. Enhanced expression levels of vascular cell adhesion molecule (VCAM)-1, tissue factor, transforming growth factor (TGF)-β and MMP-2 and 9 characterized the senescence-associated secretory phenotype of atrial ECs. In addition, the pro-senescence endothelial response to thrombin was associated with an overexpression of both angiotensin converting enzyme and AT1 receptors and was inhibited by perindoprilat and losartan. Conclusions: Thrombin promotes premature ageing and senescence of atrial ECs and may pave the way to deleterious remodeling of atrial tissue by a local up-regulation of the angiotensin system and by promoting pro-inflammatory, pro-thrombotic, pro-fibrotic and pro-remodeling responses. Hence, targeting thrombin and/or angiotensin systems may efficiently prevent atrial endothelial senescence.
Url:
DOI: 10.3390/jcm8101570
PubMed: 31581517
PubMed Central: 6833093
Affiliations:
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Thrombin Induces Angiotensin II-Mediated Senescence in Atrial Endothelial Cells: Impact on Pro-Remodeling Patterns</title>
<author><name sortKey="Hasan, Hira" sort="Hasan, Hira" uniqKey="Hasan H" first="Hira" last="Hasan">Hira Hasan</name>
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<author><name sortKey="Lee, Hyun Ho" sort="Lee, Hyun Ho" uniqKey="Lee H" first="Hyun-Ho" last="Lee">Hyun-Ho Lee</name>
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<author><name sortKey="Qureshi, Abdul Wahid" sort="Qureshi, Abdul Wahid" uniqKey="Qureshi A" first="Abdul Wahid" last="Qureshi">Abdul Wahid Qureshi</name>
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<author><name sortKey="Kauffenstein, Gilles" sort="Kauffenstein, Gilles" uniqKey="Kauffenstein G" first="Gilles" last="Kauffenstein">Gilles Kauffenstein</name>
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</author>
<author><name sortKey="Ohlmann, Patrick" sort="Ohlmann, Patrick" uniqKey="Ohlmann P" first="Patrick" last="Ohlmann">Patrick Ohlmann</name>
<affiliation><nlm:aff id="af2-jcm-08-01570">Pôle d’Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, BP 426-67091 France</nlm:aff>
<wicri:noCountry code="subfield">BP 426-67091 France</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Schini Kerth, Valerie B" sort="Schini Kerth, Valerie B" uniqKey="Schini Kerth V" first="Valérie B" last="Schini-Kerth">Valérie B. Schini-Kerth</name>
<affiliation wicri:level="4"><nlm:aff id="af1-jcm-08-01570">INSERM UMR1260 Regenerative NanoMedicine, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Faculté de Pharmacie, BP 60024 FR-67401 Strasbourg, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMR1260 Regenerative NanoMedicine, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Faculté de Pharmacie, BP 60024 FR-67401 Strasbourg</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Picardie</region>
<settlement type="city">FR-67401 Strasbourg</settlement>
</placeName>
<orgName type="university">Université de Strasbourg</orgName>
</affiliation>
</author>
<author><name sortKey="Jesel, Laurence" sort="Jesel, Laurence" uniqKey="Jesel L" first="Laurence" last="Jesel">Laurence Jesel</name>
<affiliation wicri:level="4"><nlm:aff id="af1-jcm-08-01570">INSERM UMR1260 Regenerative NanoMedicine, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Faculté de Pharmacie, BP 60024 FR-67401 Strasbourg, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMR1260 Regenerative NanoMedicine, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Faculté de Pharmacie, BP 60024 FR-67401 Strasbourg</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Picardie</region>
<settlement type="city">FR-67401 Strasbourg</settlement>
</placeName>
<orgName type="university">Université de Strasbourg</orgName>
</affiliation>
<affiliation><nlm:aff id="af2-jcm-08-01570">Pôle d’Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, BP 426-67091 France</nlm:aff>
<wicri:noCountry code="subfield">BP 426-67091 France</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Morel, Olivier" sort="Morel, Olivier" uniqKey="Morel O" first="Olivier" last="Morel">Olivier Morel</name>
<affiliation wicri:level="4"><nlm:aff id="af1-jcm-08-01570">INSERM UMR1260 Regenerative NanoMedicine, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Faculté de Pharmacie, BP 60024 FR-67401 Strasbourg, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMR1260 Regenerative NanoMedicine, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Faculté de Pharmacie, BP 60024 FR-67401 Strasbourg</wicri:regionArea>
<placeName><region type="region" nuts="2">Hauts-de-France</region>
<region type="old region" nuts="2">Picardie</region>
<settlement type="city">FR-67401 Strasbourg</settlement>
</placeName>
<orgName type="university">Université de Strasbourg</orgName>
</affiliation>
<affiliation><nlm:aff id="af2-jcm-08-01570">Pôle d’Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, BP 426-67091 France</nlm:aff>
<wicri:noCountry code="subfield">BP 426-67091 France</wicri:noCountry>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of Clinical Medicine</title>
<idno type="eISSN">2077-0383</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
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<profileDesc><textClass></textClass>
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<front><div type="abstract" xml:lang="en"><p>Background: Besides its well-known functions in hemostasis, thrombin plays a role in various non-hemostatic biological and pathophysiologic processes. We examined the potential of thrombin to promote premature atrial endothelial cells (ECs) senescence. Methods and Results: Primary ECs were isolated from porcine atrial tissue. Endothelial senescence was assessed by measuring beta-galactosidase (SA-β-gal) activity using flow cytometry, oxidative stress using the redox-sensitive probe dihydroethidium, protein level by Western blot, and matrix metalloproteinases (MMPs) activity using zymography. Atrial endothelial senescence was induced by thrombin at clinically relevant concentrations. Thrombin induced the up-regulation of p53, a key regulator in cellular senescence and of p21 and p16, two cyclin-dependent kinase inhibitors. Nicotinamide adenine dinucleotide phosphate NADPH oxidase, cyclooxygenases and the mitochondrial respiration complex contributed to oxidative stress and senescence. Enhanced expression levels of vascular cell adhesion molecule (VCAM)-1, tissue factor, transforming growth factor (TGF)-β and MMP-2 and 9 characterized the senescence-associated secretory phenotype of atrial ECs. In addition, the pro-senescence endothelial response to thrombin was associated with an overexpression of both angiotensin converting enzyme and AT1 receptors and was inhibited by perindoprilat and losartan. Conclusions: Thrombin promotes premature ageing and senescence of atrial ECs and may pave the way to deleterious remodeling of atrial tissue by a local up-regulation of the angiotensin system and by promoting pro-inflammatory, pro-thrombotic, pro-fibrotic and pro-remodeling responses. Hence, targeting thrombin and/or angiotensin systems may efficiently prevent atrial endothelial senescence.</p>
</div>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Clin Med</journal-id>
<journal-id journal-id-type="iso-abbrev">J Clin Med</journal-id>
<journal-id journal-id-type="publisher-id">jcm</journal-id>
<journal-title-group><journal-title>Journal of Clinical Medicine</journal-title>
</journal-title-group>
<issn pub-type="epub">2077-0383</issn>
<publisher><publisher-name>MDPI</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31581517</article-id>
<article-id pub-id-type="pmc">6833093</article-id>
<article-id pub-id-type="doi">10.3390/jcm8101570</article-id>
<article-id pub-id-type="publisher-id">jcm-08-01570</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Thrombin Induces Angiotensin II-Mediated Senescence in Atrial Endothelial Cells: Impact on Pro-Remodeling Patterns</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Hasan</surname>
<given-names>Hira</given-names>
</name>
<xref ref-type="aff" rid="af1-jcm-08-01570">1</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-7452-9615</contrib-id>
<name><surname>Park</surname>
<given-names>Sin-Hee</given-names>
</name>
<xref ref-type="aff" rid="af1-jcm-08-01570">1</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0003-0695-3841</contrib-id>
<name><surname>Auger</surname>
<given-names>Cyril</given-names>
</name>
<xref ref-type="aff" rid="af1-jcm-08-01570">1</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-8154-3730</contrib-id>
<name><surname>Belcastro</surname>
<given-names>Eugenia</given-names>
</name>
<xref ref-type="aff" rid="af1-jcm-08-01570">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Matsushita</surname>
<given-names>Kensuke</given-names>
</name>
<xref ref-type="aff" rid="af1-jcm-08-01570">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Marchandot</surname>
<given-names>Benjamin</given-names>
</name>
<xref ref-type="aff" rid="af2-jcm-08-01570">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lee</surname>
<given-names>Hyun-Ho</given-names>
</name>
<xref ref-type="aff" rid="af1-jcm-08-01570">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Qureshi</surname>
<given-names>Abdul Wahid</given-names>
</name>
<xref ref-type="aff" rid="af1-jcm-08-01570">1</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0003-4994-8305</contrib-id>
<name><surname>Kauffenstein</surname>
<given-names>Gilles</given-names>
</name>
<xref ref-type="aff" rid="af1-jcm-08-01570">1</xref>
<xref rid="c1-jcm-08-01570" ref-type="corresp">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ohlmann</surname>
<given-names>Patrick</given-names>
</name>
<xref ref-type="aff" rid="af2-jcm-08-01570">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schini-Kerth</surname>
<given-names>Valérie B</given-names>
</name>
<xref ref-type="aff" rid="af1-jcm-08-01570">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jesel</surname>
<given-names>Laurence</given-names>
</name>
<xref ref-type="aff" rid="af1-jcm-08-01570">1</xref>
<xref ref-type="aff" rid="af2-jcm-08-01570">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Morel</surname>
<given-names>Olivier</given-names>
</name>
<xref ref-type="aff" rid="af1-jcm-08-01570">1</xref>
<xref ref-type="aff" rid="af2-jcm-08-01570">2</xref>
<xref rid="c1-jcm-08-01570" ref-type="corresp">*</xref>
</contrib>
</contrib-group>
<aff id="af1-jcm-08-01570"><label>1</label>
INSERM UMR1260 Regenerative NanoMedicine, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Faculté de Pharmacie, BP 60024 FR-67401 Strasbourg, France</aff>
<aff id="af2-jcm-08-01570"><label>2</label>
Pôle d’Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, BP 426-67091 France</aff>
<author-notes><corresp id="c1-jcm-08-01570"><label>*</label>
Correspondence: <email>gilles.kauffenstein@gmail.com</email>
(G.K.); <email>olivier.morel@chru-strasbourg.fr</email>
(O.M.)</corresp>
</author-notes>
<pub-date pub-type="epub"><day>01</day>
<month>10</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><month>10</month>
<year>2019</year>
</pub-date>
<volume>8</volume>
<issue>10</issue>
<elocation-id>1570</elocation-id>
<history><date date-type="received"><day>29</day>
<month>8</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>25</day>
<month>9</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© 2019 by the authors.</copyright-statement>
<copyright-year>2019</copyright-year>
<license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
).</license-p>
</license>
</permissions>
<abstract><p>Background: Besides its well-known functions in hemostasis, thrombin plays a role in various non-hemostatic biological and pathophysiologic processes. We examined the potential of thrombin to promote premature atrial endothelial cells (ECs) senescence. Methods and Results: Primary ECs were isolated from porcine atrial tissue. Endothelial senescence was assessed by measuring beta-galactosidase (SA-β-gal) activity using flow cytometry, oxidative stress using the redox-sensitive probe dihydroethidium, protein level by Western blot, and matrix metalloproteinases (MMPs) activity using zymography. Atrial endothelial senescence was induced by thrombin at clinically relevant concentrations. Thrombin induced the up-regulation of p53, a key regulator in cellular senescence and of p21 and p16, two cyclin-dependent kinase inhibitors. Nicotinamide adenine dinucleotide phosphate NADPH oxidase, cyclooxygenases and the mitochondrial respiration complex contributed to oxidative stress and senescence. Enhanced expression levels of vascular cell adhesion molecule (VCAM)-1, tissue factor, transforming growth factor (TGF)-β and MMP-2 and 9 characterized the senescence-associated secretory phenotype of atrial ECs. In addition, the pro-senescence endothelial response to thrombin was associated with an overexpression of both angiotensin converting enzyme and AT1 receptors and was inhibited by perindoprilat and losartan. Conclusions: Thrombin promotes premature ageing and senescence of atrial ECs and may pave the way to deleterious remodeling of atrial tissue by a local up-regulation of the angiotensin system and by promoting pro-inflammatory, pro-thrombotic, pro-fibrotic and pro-remodeling responses. Hence, targeting thrombin and/or angiotensin systems may efficiently prevent atrial endothelial senescence.</p>
</abstract>
<kwd-group><kwd>senescence</kwd>
<kwd>thrombin</kwd>
<kwd>atrial fibrillation</kwd>
<kwd>endothelium</kwd>
<kwd>angiotensin II</kwd>
<kwd>remodeling</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group><fig id="jcm-08-01570-f001" orientation="portrait" position="float"><label>Figure 1</label>
<caption><p>Thrombin and angiotensin II (AngII) induce senescence in atrial endothelial cells (ECs) at passage 1 and are associated with an up-regulation of major cell cycle regulatory proteins: p53, p21 and p16. Atrial ECs were either untreated or exposed to thrombin (1 or 3 U/mL) or AngII (100 nM) for 24 h before determination of senescence by SA-β-galactosidase (SA-β gal) activity (<bold>A</bold>
) and protein expression level of (<bold>B</bold>
) p53, (<bold>C</bold>
) p21 and (<bold>D</bold>
) p16 by Western blot analysis. Results are presented as representative immunoblots (upper panels), and corresponding cumulative data (lower panels) and are shown as mean ± SEM of <italic>n</italic>
= 3–4 different experiments. *<italic>P</italic>
< 0.05 versus respective control.</p>
</caption>
<graphic xlink:href="jcm-08-01570-g001"></graphic>
</fig>
<fig id="jcm-08-01570-f002" orientation="portrait" position="float"><label>Figure 2</label>
<caption><p>Thrombin induces oxidative stress promoting senescence in atrial ECs. (<bold>A</bold>
) Atrial ECs were either untreated or exposed to N-acetylcysteine (NAC, an antioxidant), VAS-2870 (VAS, NADPH oxidase inhibitor), indomethacin (INDO, COX inhibitor), SC-560 (COX-1 inhibitor), NS-398 (COX-2 inhibitor) or a mitochondrial inhibitory complex (MIH; rotenone; KCN; myxothiazole) before the addition of thrombin (1 U/mL, 1 h) and dihydroethidium (DHE) to determine the level of oxidative stress by confocal microscopy. Upper panels represent ethidium staining and lower panel corresponds to cumulative data. (<bold>B</bold>
) Atrial ECs were either untreated or exposed to NAC, VAS, INDO or MIH before the addition of thrombin (1 U/mL, 24 h) and subsequent determination of SA-β-gal activity using flow cytometry. Results are shown as mean ± SEM of <italic>n</italic>
= 3–4 different experiments. *<italic>P</italic>
< 0.05 versus respective control, <sup>#</sup>
<italic>P</italic>
< 0.05 versus thrombin-treated atrial ECs.</p>
</caption>
<graphic xlink:href="jcm-08-01570-g002a"></graphic>
<graphic xlink:href="jcm-08-01570-g002b"></graphic>
</fig>
<fig id="jcm-08-01570-f003" orientation="portrait" position="float"><label>Figure 3</label>
<caption><p>Thrombin and AngII induce the expression of cyclooxygenase-2 in atrial ECs. Atrial ECs were either untreated or exposed to thrombin (1 or 3 U/mL) or AngII (100 nM) before determination of the expression level of (<bold>A</bold>
) COX-1 and (<bold>B</bold>
) COX-2, as assessed by Western blot analysis. Results are shown as representative immunoblots (upper panels) and corresponding cumulative data (lower panels) and shown as mean ± SEM, <italic>n</italic>
= 3–4, *<italic>P</italic>
< 0.05 versus respective control.</p>
</caption>
<graphic xlink:href="jcm-08-01570-g003"></graphic>
</fig>
<fig id="jcm-08-01570-f004" orientation="portrait" position="float"><label>Figure 4</label>
<caption><p>Thrombin- and AngII-induced senescence promotes pro-inflammatory and pro-coagulant phenotype in atrial ECs. Atrial ECs were untreated or exposed to either thrombin (1 or 3 U/mL) or AngII (100 nM) before determination of the expression level of target proteins, as assessed by Western blot analysis. Results are shown as representative immunoblots (upper panels) and corresponding cumulative data (lower panels) and shown as mean ± SEM, <italic>n</italic>
= 3–4, *<italic>P</italic>
< 0.05 versus respective control.</p>
</caption>
<graphic xlink:href="jcm-08-01570-g004"></graphic>
</fig>
<fig id="jcm-08-01570-f005" orientation="portrait" position="float"><label>Figure 5</label>
<caption><p>Thrombin- and AngII-induced senescence promotes pro-fibrotic phenotype in atrial ECs. Atrial ECs were untreated or exposed to either thrombin (1 or 3 U/mL) or AngII (100 nM) before determination of the expression level of TGF-β (<bold>A</bold>
) as assessed by Western blot analysis, and MMP-2 and 9 activities by zymography (<bold>B, C</bold>
). Results are shown as representative immunoblots or gelatinolytic activity (upper panels) and corresponding cumulative data (lower panels) and shown as mean ± SEM, <italic>n</italic>
= 3–4, *<italic>P</italic>
< 0.05 versus respective control.</p>
</caption>
<graphic xlink:href="jcm-08-01570-g005"></graphic>
</fig>
<fig id="jcm-08-01570-f006" orientation="portrait" position="float"><label>Figure 6</label>
<caption><p>Thrombin-induced senescence promotes up-regulation of the local angiotensin system in atrial ECs. Atrial ECs were either untreated or exposed to losartan (AT1R antagonist) or perindoprilat (ACE inhibitor) before the addition of thrombin (1 U/mL) or AngII (100 nM) for 24 h, and the subsequent determination of the expression level of target proteins (<bold>A, B</bold>
) as assessed by Western blot analysis, (<bold>C</bold>
) oxidative stress by confocal microscopy, and (<bold>D</bold>
) SA-β-gal activity using flow cytometry. Results are shown as representative immunoblots (upper panels) and corresponding cumulative data (lower panels) and shown as mean ± SEM, <italic>n</italic>
= 3–4, *<italic>P</italic>
< 0.05 versus respective control, <sup>#</sup>
<italic>P</italic>
< 0.05 versus thrombin-treated atrial ECs.</p>
</caption>
<graphic xlink:href="jcm-08-01570-g006"></graphic>
</fig>
</floats-group>
</pmc>
<affiliations><list><country><li>France</li>
</country>
<region><li>Hauts-de-France</li>
<li>Picardie</li>
</region>
<settlement><li>FR-67401 Strasbourg</li>
</settlement>
<orgName><li>Université de Strasbourg</li>
</orgName>
</list>
<tree><noCountry><name sortKey="Marchandot, Benjamin" sort="Marchandot, Benjamin" uniqKey="Marchandot B" first="Benjamin" last="Marchandot">Benjamin Marchandot</name>
<name sortKey="Ohlmann, Patrick" sort="Ohlmann, Patrick" uniqKey="Ohlmann P" first="Patrick" last="Ohlmann">Patrick Ohlmann</name>
</noCountry>
<country name="France"><region name="Hauts-de-France"><name sortKey="Hasan, Hira" sort="Hasan, Hira" uniqKey="Hasan H" first="Hira" last="Hasan">Hira Hasan</name>
</region>
<name sortKey="Auger, Cyril" sort="Auger, Cyril" uniqKey="Auger C" first="Cyril" last="Auger">Cyril Auger</name>
<name sortKey="Belcastro, Eugenia" sort="Belcastro, Eugenia" uniqKey="Belcastro E" first="Eugenia" last="Belcastro">Eugenia Belcastro</name>
<name sortKey="Jesel, Laurence" sort="Jesel, Laurence" uniqKey="Jesel L" first="Laurence" last="Jesel">Laurence Jesel</name>
<name sortKey="Kauffenstein, Gilles" sort="Kauffenstein, Gilles" uniqKey="Kauffenstein G" first="Gilles" last="Kauffenstein">Gilles Kauffenstein</name>
<name sortKey="Lee, Hyun Ho" sort="Lee, Hyun Ho" uniqKey="Lee H" first="Hyun-Ho" last="Lee">Hyun-Ho Lee</name>
<name sortKey="Matsushita, Kensuke" sort="Matsushita, Kensuke" uniqKey="Matsushita K" first="Kensuke" last="Matsushita">Kensuke Matsushita</name>
<name sortKey="Morel, Olivier" sort="Morel, Olivier" uniqKey="Morel O" first="Olivier" last="Morel">Olivier Morel</name>
<name sortKey="Park, Sin Hee" sort="Park, Sin Hee" uniqKey="Park S" first="Sin-Hee" last="Park">Sin-Hee Park</name>
<name sortKey="Qureshi, Abdul Wahid" sort="Qureshi, Abdul Wahid" uniqKey="Qureshi A" first="Abdul Wahid" last="Qureshi">Abdul Wahid Qureshi</name>
<name sortKey="Schini Kerth, Valerie B" sort="Schini Kerth, Valerie B" uniqKey="Schini Kerth V" first="Valérie B" last="Schini-Kerth">Valérie B. Schini-Kerth</name>
</country>
</tree>
</affiliations>
</record>
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