AustralieFrV1, Main, Exploration, bibRecord, 004C91

Right Ventricular Diastolic Impairment in Patients With Pulmonary Arterial Hypertension

Identifieur interne : 004C91 ( Main/Exploration ); précédent : 004C90; suivant : 004C92

Right Ventricular Diastolic Impairment in Patients With Pulmonary Arterial Hypertension

Auteurs : Silvia Rain [Pays-Bas] ; M. Louis Handoko [Pays-Bas] ; Pia Trip [Pays-Bas] ; C. Tji-Joong Gan [Pays-Bas] ; Nico Westerhof [Pays-Bas] ; Ger J. Stienen [Pays-Bas] ; Walter J. Paulus [Pays-Bas] ; Coen A. C. Ottenheijm [Pays-Bas] ; J. Tim Marcus [Pays-Bas] ; Peter Dorfmüller [France] ; Christophe Guignabert [France] ; Marc Humbert [France] ; Peter Macdonald [Australie] ; Cris Dos Remedios [Australie] ; Piet E. Postmus [Pays-Bas] ; Chandra Saripalli [États-Unis] ; Carlos G. Hidalgo [États-Unis] ; Henk L. Granzier [États-Unis] ; Anton Vonk-Noordegraaf [Pays-Bas] ; Jolanda Van Der Velden [Pays-Bas] ; Frances S. De Man [Pays-Bas]

Source :

Circulation : (New York, N.Y.) [ 0009-7322 ] ; 2013.

RBID : Pascal:13-0356079

Descripteurs français

Pascal (Inist)
- Hypertension artérielle pulmonaire, Insuffisance cardiaque, Hypertension artérielle, Pathologie de l'appareil circulatoire, Ventricule droit, Homme, Malade, Artère, Diastole, Poumon, Sarcomère, Appareil circulatoire, Cardiologie.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Artery, Cardiology, Cardiovascular disease, Circulatory system, Diastole, Heart failure, Human, Hypertension, Lung, Patient, Pulmonary hypertension, Right ventricle, Sarcomere.

Abstract

Background-The role of right ventricular (RV) diastolic stiffness in pulmonary arterial hypertension (PAH) is not well established. Therefore, we investigated the presence and possible underlying mechanisms of RV diastolic stiffness in PAH patients. Methods and Results-Single-beat RV pressure-volume analyses were performed in 21 PAH patients and 7 control subjects to study RV diastolic stiffness. Data are presented as mean±SEM. RV diastolic stiffness (β) was significantly increased in PAH patients (PAH, 0.050±0.005 versus control, 0.029±0.003; P<0.05) and was closely associated with disease severity. Subsequently, we searched for possible underlying mechanisms using RV tissue of PAH patients undergoing heart/lung transplantation and nonfailing donors. Histological analyses revealed increased cardiomyocyte cross-sectional areas (PAH, 453±31 μm² versus control, 218±21 μm²; P<0.001), indicating RV hypertrophy. In addition, the amount of RV fibrosis was enhanced in PAH tissue (PAH, 9.6±0.7% versus control, 7.2±0.6%; P<0.01). To investigate the contribution of stiffening of the sarcomere (the contractile apparatus of RV cardiomyocytes) to RV diastolic stiffness, we isolated and membrane-permeabilized single RV cardiomyocytes. Passive tension at different sarcomere lengths was significantly higher in PAH patients compared with control subjects (>200%; P_interaction<0.001), indicating stiffening of RV sarcomeres. An important regulator of sarcomeric stiffening is the sarcomeric protein titin. Therefore, we investigated titin isoform composition and phosphorylation. No alterations were observed in titin isoform composition (N2BA/N2B ratio: PAH, 0.78±0.07 versus control, 0.91±0.08), but titin phosphorylation in RV tissue of PAH patients was significantly reduced (PAH, 0.16±0.01 arbitrary units versus control, 0.20±0.01 arbitrary units; P<0.05). Conclusions-RV diastolic stiffness is significantly increased in PAH patients, with important contributions from increased collagen and intrinsic stiffening of the RV cardiomyocyte sarcomeres.

Affiliations:

Links toward previous steps (curation, corpus...)

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Le document en format XML

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<author><name sortKey="Macdonald, Peter" sort="Macdonald, Peter" uniqKey="Macdonald P" first="Peter" last="Macdonald">Peter Macdonald</name>
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<author><name sortKey="Remedios, Cris Dos" sort="Remedios, Cris Dos" uniqKey="Remedios C" first="Cris Dos" last="Remedios">Cris Dos Remedios</name>
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<author><name sortKey="Van Der Velden, Jolanda" sort="Van Der Velden, Jolanda" uniqKey="Van Der Velden J" first="Jolanda" last="Van Der Velden">Jolanda Van Der Velden</name>
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<region nuts="2" type="province">Utrecht (province)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="De Man, Frances S" sort="De Man, Frances S" uniqKey="De Man F" first="Frances S." last="De Man">Frances S. De Man</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
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</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Physiology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
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<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
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</placeName>
</affiliation>
</author>
</titleStmt>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Right Ventricular Diastolic Impairment in Patients With Pulmonary Arterial Hypertension</title>
<author><name sortKey="Rain, Silvia" sort="Rain, Silvia" uniqKey="Rain S" first="Silvia" last="Rain">Silvia Rain</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
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</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Physiology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Handoko, M Louis" sort="Handoko, M Louis" uniqKey="Handoko M" first="M. Louis" last="Handoko">M. Louis Handoko</name>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Physiology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
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</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Cardiology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>2 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Trip, Pia" sort="Trip, Pia" uniqKey="Trip P" first="Pia" last="Trip">Pia Trip</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>15 aut.</sZ>
<sZ>19 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gan, C Tji Joong" sort="Gan, C Tji Joong" uniqKey="Gan C" first="C. Tji-Joong" last="Gan">C. Tji-Joong Gan</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>15 aut.</sZ>
<sZ>19 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Westerhof, Nico" sort="Westerhof, Nico" uniqKey="Westerhof N" first="Nico" last="Westerhof">Nico Westerhof</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>15 aut.</sZ>
<sZ>19 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Physiology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>20 aut.</sZ>
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</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stienen, Ger J" sort="Stienen, Ger J" uniqKey="Stienen G" first="Ger J." last="Stienen">Ger J. Stienen</name>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Physiology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>20 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Paulus, Walter J" sort="Paulus, Walter J" uniqKey="Paulus W" first="Walter J." last="Paulus">Walter J. Paulus</name>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Physiology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>20 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ottenheijm, Coen A C" sort="Ottenheijm, Coen A C" uniqKey="Ottenheijm C" first="Coen A. C." last="Ottenheijm">Coen A. C. Ottenheijm</name>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Physiology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>20 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Marcus, J Tim" sort="Marcus, J Tim" uniqKey="Marcus J" first="J. Tim" last="Marcus">J. Tim Marcus</name>
<affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Medical Physics, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dorfmuller, Peter" sort="Dorfmuller, Peter" uniqKey="Dorfmuller P" first="Peter" last="Dorfmüller">Peter Dorfmüller</name>
<affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Université Paris-Sud</s1>
<s2>Le Kremlin-Bicêtre</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Université Paris-Sud</wicri:noRegion>
<placeName><settlement type="city">Orsay</settlement>
<region type="region" nuts="2">Île-de-France</region>
</placeName>
<orgName type="university">Université Paris-Sud</orgName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>INSERM UMR 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue</s1>
<s2>Le Plessis Robinson</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Le Plessis Robinson</wicri:noRegion>
<wicri:noRegion>Centre Chirurgical Marie Lannelongue</wicri:noRegion>
<wicri:noRegion>Le Plessis Robinson</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Guignabert, Christophe" sort="Guignabert, Christophe" uniqKey="Guignabert C" first="Christophe" last="Guignabert">Christophe Guignabert</name>
<affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Université Paris-Sud</s1>
<s2>Le Kremlin-Bicêtre</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Université Paris-Sud</wicri:noRegion>
<placeName><settlement type="city">Orsay</settlement>
<region type="region" nuts="2">Île-de-France</region>
</placeName>
<orgName type="university">Université Paris-Sud</orgName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>INSERM UMR 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue</s1>
<s2>Le Plessis Robinson</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Le Plessis Robinson</wicri:noRegion>
<wicri:noRegion>Centre Chirurgical Marie Lannelongue</wicri:noRegion>
<wicri:noRegion>Le Plessis Robinson</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Humbert, Marc" sort="Humbert, Marc" uniqKey="Humbert M" first="Marc" last="Humbert">Marc Humbert</name>
<affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Université Paris-Sud</s1>
<s2>Le Kremlin-Bicêtre</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Université Paris-Sud</wicri:noRegion>
<placeName><settlement type="city">Orsay</settlement>
<region type="region" nuts="2">Île-de-France</region>
</placeName>
<orgName type="university">Université Paris-Sud</orgName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>INSERM UMR 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue</s1>
<s2>Le Plessis Robinson</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Le Plessis Robinson</wicri:noRegion>
<wicri:noRegion>Centre Chirurgical Marie Lannelongue</wicri:noRegion>
<wicri:noRegion>Le Plessis Robinson</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="07"><s1>AP-HP, Hôpital de Bicêtre, Service de Pneumologie, DHU Thorax Innovation</s1>
<s2>Le Kremlin-Bicêtre</s2>
<s3>FRA</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Le Kremlin-Bicêtre</wicri:noRegion>
<wicri:noRegion>DHU Thorax Innovation</wicri:noRegion>
<wicri:noRegion>Le Kremlin-Bicêtre</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Macdonald, Peter" sort="Macdonald, Peter" uniqKey="Macdonald P" first="Peter" last="Macdonald">Peter Macdonald</name>
<affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Heart & Lung Transplant Unit, St. Vincent's Hospital and Victor Chang Cardiac Research Institute</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Remedios, Cris Dos" sort="Remedios, Cris Dos" uniqKey="Remedios C" first="Cris Dos" last="Remedios">Cris Dos Remedios</name>
<affiliation wicri:level="4"><inist:fA14 i1="09"><s1>Muscle Research Unit, Institute for Biomedical Research, University of Sydney</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<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="Postmus, Piet E" sort="Postmus, Piet E" uniqKey="Postmus P" first="Piet E." last="Postmus">Piet E. Postmus</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>15 aut.</sZ>
<sZ>19 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Saripalli, Chandra" sort="Saripalli, Chandra" uniqKey="Saripalli C" first="Chandra" last="Saripalli">Chandra Saripalli</name>
<affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Sarver Molecular Cardiovascular Research Program, Department of Physiology, University of Arizona</s1>
<s2>Tucson</s2>
<s3>USA</s3>
<sZ>16 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Tucson</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hidalgo, Carlos G" sort="Hidalgo, Carlos G" uniqKey="Hidalgo C" first="Carlos G." last="Hidalgo">Carlos G. Hidalgo</name>
<affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Sarver Molecular Cardiovascular Research Program, Department of Physiology, University of Arizona</s1>
<s2>Tucson</s2>
<s3>USA</s3>
<sZ>16 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Tucson</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Granzier, Henk L" sort="Granzier, Henk L" uniqKey="Granzier H" first="Henk L." last="Granzier">Henk L. Granzier</name>
<affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Sarver Molecular Cardiovascular Research Program, Department of Physiology, University of Arizona</s1>
<s2>Tucson</s2>
<s3>USA</s3>
<sZ>16 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Tucson</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Vonk Noordegraaf, Anton" sort="Vonk Noordegraaf, Anton" uniqKey="Vonk Noordegraaf A" first="Anton" last="Vonk-Noordegraaf">Anton Vonk-Noordegraaf</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>15 aut.</sZ>
<sZ>19 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Van Der Velden, Jolanda" sort="Van Der Velden, Jolanda" uniqKey="Van Der Velden J" first="Jolanda" last="Van Der Velden">Jolanda Van Der Velden</name>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Physiology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>20 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="11"><s1>ICIN-The Netherlands Heart Institute</s1>
<s2>Utrecht</s2>
<s3>NLD</s3>
<sZ>20 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Utrecht</settlement>
<region nuts="2" type="province">Utrecht (province)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="De Man, Frances S" sort="De Man, Frances S" uniqKey="De Man F" first="Frances S." last="De Man">Frances S. De Man</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>15 aut.</sZ>
<sZ>19 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Physiology, VU University Medical Center/Institute for Cardiovascular Research</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>20 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Circulation : (New York, N.Y.)</title>
<title level="j" type="abbreviated">Circulation : (N. Y. N.Y.)</title>
<idno type="ISSN">0009-7322</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Circulation : (New York, N.Y.)</title>
<title level="j" type="abbreviated">Circulation : (N. Y. N.Y.)</title>
<idno type="ISSN">0009-7322</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Artery</term>
<term>Cardiology</term>
<term>Cardiovascular disease</term>
<term>Circulatory system</term>
<term>Diastole</term>
<term>Heart failure</term>
<term>Human</term>
<term>Hypertension</term>
<term>Lung</term>
<term>Patient</term>
<term>Pulmonary hypertension</term>
<term>Right ventricle</term>
<term>Sarcomere</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Hypertension artérielle pulmonaire</term>
<term>Insuffisance cardiaque</term>
<term>Hypertension artérielle</term>
<term>Pathologie de l'appareil circulatoire</term>
<term>Ventricule droit</term>
<term>Homme</term>
<term>Malade</term>
<term>Artère</term>
<term>Diastole</term>
<term>Poumon</term>
<term>Sarcomère</term>
<term>Appareil circulatoire</term>
<term>Cardiologie</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Background-The role of right ventricular (RV) diastolic stiffness in pulmonary arterial hypertension (PAH) is not well established. Therefore, we investigated the presence and possible underlying mechanisms of RV diastolic stiffness in PAH patients. Methods and Results-Single-beat RV pressure-volume analyses were performed in 21 PAH patients and 7 control subjects to study RV diastolic stiffness. Data are presented as mean±SEM. RV diastolic stiffness (β) was significantly increased in PAH patients (PAH, 0.050±0.005 versus control, 0.029±0.003; P<0.05) and was closely associated with disease severity. Subsequently, we searched for possible underlying mechanisms using RV tissue of PAH patients undergoing heart/lung transplantation and nonfailing donors. Histological analyses revealed increased cardiomyocyte cross-sectional areas (PAH, 453±31 μm<sup>2</sup>
 versus control, 218±21 μm<sup>2</sup>
; P<0.001), indicating RV hypertrophy. In addition, the amount of RV fibrosis was enhanced in PAH tissue (PAH, 9.6±0.7% versus control, 7.2±0.6%; P<0.01). To investigate the contribution of stiffening of the sarcomere (the contractile apparatus of RV cardiomyocytes) to RV diastolic stiffness, we isolated and membrane-permeabilized single RV cardiomyocytes. Passive tension at different sarcomere lengths was significantly higher in PAH patients compared with control subjects (>200%; P<sub>interaction</sub>
<0.001), indicating stiffening of RV sarcomeres. An important regulator of sarcomeric stiffening is the sarcomeric protein titin. Therefore, we investigated titin isoform composition and phosphorylation. No alterations were observed in titin isoform composition (N2BA/N2B ratio: PAH, 0.78±0.07 versus control, 0.91±0.08), but titin phosphorylation in RV tissue of PAH patients was significantly reduced (PAH, 0.16±0.01 arbitrary units versus control, 0.20±0.01 arbitrary units; P<0.05). Conclusions-RV diastolic stiffness is significantly increased in PAH patients, with important contributions from increased collagen and intrinsic stiffening of the RV cardiomyocyte sarcomeres.</div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>France</li>
<li>Pays-Bas</li>
<li>États-Unis</li>
</country>
<region><li>Hollande-Septentrionale</li>
<li>Nouvelle-Galles du Sud</li>
<li>Utrecht (province)</li>
<li>Île-de-France</li>
</region>
<settlement><li>Amsterdam</li>
<li>Orsay</li>
<li>Sydney</li>
<li>Utrecht</li>
</settlement>
<orgName><li>Université Paris-Sud</li>
<li>Université de Sydney</li>
</orgName>
</list>
<tree><country name="Pays-Bas"><region name="Hollande-Septentrionale"><name sortKey="Rain, Silvia" sort="Rain, Silvia" uniqKey="Rain S" first="Silvia" last="Rain">Silvia Rain</name>
</region>
<name sortKey="De Man, Frances S" sort="De Man, Frances S" uniqKey="De Man F" first="Frances S." last="De Man">Frances S. De Man</name>
<name sortKey="De Man, Frances S" sort="De Man, Frances S" uniqKey="De Man F" first="Frances S." last="De Man">Frances S. De Man</name>
<name sortKey="Gan, C Tji Joong" sort="Gan, C Tji Joong" uniqKey="Gan C" first="C. Tji-Joong" last="Gan">C. Tji-Joong Gan</name>
<name sortKey="Handoko, M Louis" sort="Handoko, M Louis" uniqKey="Handoko M" first="M. Louis" last="Handoko">M. Louis Handoko</name>
<name sortKey="Handoko, M Louis" sort="Handoko, M Louis" uniqKey="Handoko M" first="M. Louis" last="Handoko">M. Louis Handoko</name>
<name sortKey="Marcus, J Tim" sort="Marcus, J Tim" uniqKey="Marcus J" first="J. Tim" last="Marcus">J. Tim Marcus</name>
<name sortKey="Ottenheijm, Coen A C" sort="Ottenheijm, Coen A C" uniqKey="Ottenheijm C" first="Coen A. C." last="Ottenheijm">Coen A. C. Ottenheijm</name>
<name sortKey="Paulus, Walter J" sort="Paulus, Walter J" uniqKey="Paulus W" first="Walter J." last="Paulus">Walter J. Paulus</name>
<name sortKey="Postmus, Piet E" sort="Postmus, Piet E" uniqKey="Postmus P" first="Piet E." last="Postmus">Piet E. Postmus</name>
<name sortKey="Rain, Silvia" sort="Rain, Silvia" uniqKey="Rain S" first="Silvia" last="Rain">Silvia Rain</name>
<name sortKey="Stienen, Ger J" sort="Stienen, Ger J" uniqKey="Stienen G" first="Ger J." last="Stienen">Ger J. Stienen</name>
<name sortKey="Trip, Pia" sort="Trip, Pia" uniqKey="Trip P" first="Pia" last="Trip">Pia Trip</name>
<name sortKey="Van Der Velden, Jolanda" sort="Van Der Velden, Jolanda" uniqKey="Van Der Velden J" first="Jolanda" last="Van Der Velden">Jolanda Van Der Velden</name>
<name sortKey="Van Der Velden, Jolanda" sort="Van Der Velden, Jolanda" uniqKey="Van Der Velden J" first="Jolanda" last="Van Der Velden">Jolanda Van Der Velden</name>
<name sortKey="Vonk Noordegraaf, Anton" sort="Vonk Noordegraaf, Anton" uniqKey="Vonk Noordegraaf A" first="Anton" last="Vonk-Noordegraaf">Anton Vonk-Noordegraaf</name>
<name sortKey="Westerhof, Nico" sort="Westerhof, Nico" uniqKey="Westerhof N" first="Nico" last="Westerhof">Nico Westerhof</name>
<name sortKey="Westerhof, Nico" sort="Westerhof, Nico" uniqKey="Westerhof N" first="Nico" last="Westerhof">Nico Westerhof</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Dorfmuller, Peter" sort="Dorfmuller, Peter" uniqKey="Dorfmuller P" first="Peter" last="Dorfmüller">Peter Dorfmüller</name>
</region>
<name sortKey="Dorfmuller, Peter" sort="Dorfmuller, Peter" uniqKey="Dorfmuller P" first="Peter" last="Dorfmüller">Peter Dorfmüller</name>
<name sortKey="Guignabert, Christophe" sort="Guignabert, Christophe" uniqKey="Guignabert C" first="Christophe" last="Guignabert">Christophe Guignabert</name>
<name sortKey="Guignabert, Christophe" sort="Guignabert, Christophe" uniqKey="Guignabert C" first="Christophe" last="Guignabert">Christophe Guignabert</name>
<name sortKey="Humbert, Marc" sort="Humbert, Marc" uniqKey="Humbert M" first="Marc" last="Humbert">Marc Humbert</name>
<name sortKey="Humbert, Marc" sort="Humbert, Marc" uniqKey="Humbert M" first="Marc" last="Humbert">Marc Humbert</name>
<name sortKey="Humbert, Marc" sort="Humbert, Marc" uniqKey="Humbert M" first="Marc" last="Humbert">Marc Humbert</name>
</country>
<country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Macdonald, Peter" sort="Macdonald, Peter" uniqKey="Macdonald P" first="Peter" last="Macdonald">Peter Macdonald</name>
</region>
<name sortKey="Remedios, Cris Dos" sort="Remedios, Cris Dos" uniqKey="Remedios C" first="Cris Dos" last="Remedios">Cris Dos Remedios</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Saripalli, Chandra" sort="Saripalli, Chandra" uniqKey="Saripalli C" first="Chandra" last="Saripalli">Chandra Saripalli</name>
</noRegion>
<name sortKey="Granzier, Henk L" sort="Granzier, Henk L" uniqKey="Granzier H" first="Henk L." last="Granzier">Henk L. Granzier</name>
<name sortKey="Hidalgo, Carlos G" sort="Hidalgo, Carlos G" uniqKey="Hidalgo C" first="Carlos G." last="Hidalgo">Carlos G. Hidalgo</name>
</country>
</tree>
</affiliations>
</record>

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Right Ventricular Diastolic Impairment in Patients With Pulmonary Arterial Hypertension

Right Ventricular Diastolic Impairment in Patients With Pulmonary Arterial Hypertension

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