Bone Morphogenetic Protein Receptor Type 2 Mutation in Pulmonary Arterial Hypertension: A View on the Right Ventricle
BACKGROUND—The effect of a mutation in the bone morphogenetic protein receptor 2 gene (BMPR2) gene on right ventricular (RV) pressure overload in patients with pulmonary arterial hypertension (PAH) is unknown. Therefore, we investigated RV function in PAH-patients with and without BMPR2 mutation by...
Gespeichert in:
| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2016-05, Vol.133 (18), p.1747-1760 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1760 |
|---|---|
| container_issue | 18 |
| container_start_page | 1747 |
| container_title | Circulation (New York, N.Y.) |
| container_volume | 133 |
| creator | Van Der Bruggen, Cathelijne E.E Happé, Chris M Dorfmuller, Peter Trip, Pia Spruijt, Onno A Rol, Nina Hoevenaars, Femke P Houweling, Arjan C Girerd, Barbara Marcus, Johannes T Mercier, Olaf Humbert, Marc Handoko, M Louis Van Der Velden, Jolanda Noordegraaf, Anton Vonk Bogaard, Harm Jan Goumans, Marie-José de Man, Frances S |
| description | BACKGROUND—The effect of a mutation in the bone morphogenetic protein receptor 2 gene (BMPR2) gene on right ventricular (RV) pressure overload in patients with pulmonary arterial hypertension (PAH) is unknown. Therefore, we investigated RV function in PAH-patients with and without BMPR2 mutation by combining in vivo measurements with molecular and histological analysis of human RV and left ventricular (LV) tissue.
METHODS AND RESULTS—In total, 95 idiopathic or familial PAH patients were genetically screened for the presence of a BMPR2 mutation28 patients had a BMPR2 mutation, 67 patients did not have a BMPR2 mutation. In vivo measurements were assessed using right heart catheterization (RHC) and cardiac magnetic resonance imaging. Despite a similar mean pulmonary artery pressure (non-carriers 54±15 vs. mutation carriers 55±9 mmHg) and pulmonary vascular resistance (755 (483-1043) vs. 931 (624-1311) dynes*s/cm), mutation carriers presented with a more severely compromised RV function (RV ejection fraction37.6±12.8 vs. 29.0±9 %p |
| doi_str_mv | 10.1161/CIRCULATIONAHA.115.020696 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1787085889</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1787085889</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3156-54e86b26188e129c4f141ecf5169f54755710b5ead06fb10856bb50d8e03fd533</originalsourceid><addsrcrecordid>eNqNkE1PxCAQhonR6PrxFwzevFShLRRMPNSNupusH9msXpu2O7UoWyrQbPz3YlZNvHkChuedyTwInVByRimn5-PpfPw0yxfTh_t8kocaOyMx4ZJvoRFlcRqlLJHbaEQIkVGWxPEe2nfuNTx5krFdtBdzKVKZiBEarkwH-M7YvjUv0IFXNX60xoPq8Bxq6L2xePHRA47x3eBLr0yHw9_joFemK-0Hzq0Hq0qNJ4EK984F5ALn-FnBGgfat4Dn6qX1-Bk6b1Wt4RDtNKV2cPR9HqCnm-vFeBLNHm6n43wW1QllPGIpCF7FnAoBNJZ12tCUQt0wymXD0oyxjJKKQbkkvKkoEYxXFSNLASRplixJDtDppm9vzfsAzhcr5WrQuuzADK6gmchCSggZULlBa2ucs9AUvVWrsGBBSfFlvfhrPdRYsbEessffY4ZqBcvf5I_mAFxugLXRwZZ708MabNFCqX37jwGfpzSTFA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1787085889</pqid></control><display><type>article</type><title>Bone Morphogenetic Protein Receptor Type 2 Mutation in Pulmonary Arterial Hypertension: A View on the Right Ventricle</title><source>MEDLINE</source><source>American Heart Association Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Journals@Ovid Complete</source><creator>Van Der Bruggen, Cathelijne E.E ; Happé, Chris M ; Dorfmuller, Peter ; Trip, Pia ; Spruijt, Onno A ; Rol, Nina ; Hoevenaars, Femke P ; Houweling, Arjan C ; Girerd, Barbara ; Marcus, Johannes T ; Mercier, Olaf ; Humbert, Marc ; Handoko, M Louis ; Van Der Velden, Jolanda ; Noordegraaf, Anton Vonk ; Bogaard, Harm Jan ; Goumans, Marie-José ; de Man, Frances S</creator><creatorcontrib>Van Der Bruggen, Cathelijne E.E ; Happé, Chris M ; Dorfmuller, Peter ; Trip, Pia ; Spruijt, Onno A ; Rol, Nina ; Hoevenaars, Femke P ; Houweling, Arjan C ; Girerd, Barbara ; Marcus, Johannes T ; Mercier, Olaf ; Humbert, Marc ; Handoko, M Louis ; Van Der Velden, Jolanda ; Noordegraaf, Anton Vonk ; Bogaard, Harm Jan ; Goumans, Marie-José ; de Man, Frances S</creatorcontrib><description>BACKGROUND—The effect of a mutation in the bone morphogenetic protein receptor 2 gene (BMPR2) gene on right ventricular (RV) pressure overload in patients with pulmonary arterial hypertension (PAH) is unknown. Therefore, we investigated RV function in PAH-patients with and without BMPR2 mutation by combining in vivo measurements with molecular and histological analysis of human RV and left ventricular (LV) tissue.
METHODS AND RESULTS—In total, 95 idiopathic or familial PAH patients were genetically screened for the presence of a BMPR2 mutation28 patients had a BMPR2 mutation, 67 patients did not have a BMPR2 mutation. In vivo measurements were assessed using right heart catheterization (RHC) and cardiac magnetic resonance imaging. Despite a similar mean pulmonary artery pressure (non-carriers 54±15 vs. mutation carriers 55±9 mmHg) and pulmonary vascular resistance (755 (483-1043) vs. 931 (624-1311) dynes*s/cm), mutation carriers presented with a more severely compromised RV function (RV ejection fraction37.6±12.8 vs. 29.0±9 %p<0.05, cardiac index 2.7±0.9 vs. 2.2±0.4 l/min/m). Differences continued to exist after treatment. To investigate the role of TGF-β and BMPRII signaling, human RV and LV tissue were studied in controls (n=6), mutation carriers (n=5) and non-carriers (n=11). However, TGF-β and BMPRII signaling, as well as hypertrophy, apoptosis, fibrosis, capillary density, inflammation and cardiac metabolism were similar between mutation carriers and non-carriers.
CONCLUSIONS—Despite a similar afterload, RV function is more severely affected in mutation carriers compared to non-carriers. However, these differences cannot be explained by a differential TGF-β, BMPRII signaling or cardiac adaptation.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/CIRCULATIONAHA.115.020696</identifier><identifier>PMID: 26984938</identifier><language>eng</language><publisher>United States: by the American College of Cardiology Foundation and the American Heart Association, Inc</publisher><subject>Adult ; Aged ; Bone Morphogenetic Protein Receptors, Type II - genetics ; Female ; Humans ; Hypertension, Pulmonary - diagnosis ; Hypertension, Pulmonary - genetics ; Male ; Middle Aged ; Mutation - genetics ; Retrospective Studies ; Ventricular Dysfunction, Right - diagnosis ; Ventricular Dysfunction, Right - genetics ; Ventricular Function, Right - genetics</subject><ispartof>Circulation (New York, N.Y.), 2016-05, Vol.133 (18), p.1747-1760</ispartof><rights>2016 by the American College of Cardiology Foundation and the American Heart Association, Inc.</rights><rights>2016 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3156-54e86b26188e129c4f141ecf5169f54755710b5ead06fb10856bb50d8e03fd533</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26984938$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Van Der Bruggen, Cathelijne E.E</creatorcontrib><creatorcontrib>Happé, Chris M</creatorcontrib><creatorcontrib>Dorfmuller, Peter</creatorcontrib><creatorcontrib>Trip, Pia</creatorcontrib><creatorcontrib>Spruijt, Onno A</creatorcontrib><creatorcontrib>Rol, Nina</creatorcontrib><creatorcontrib>Hoevenaars, Femke P</creatorcontrib><creatorcontrib>Houweling, Arjan C</creatorcontrib><creatorcontrib>Girerd, Barbara</creatorcontrib><creatorcontrib>Marcus, Johannes T</creatorcontrib><creatorcontrib>Mercier, Olaf</creatorcontrib><creatorcontrib>Humbert, Marc</creatorcontrib><creatorcontrib>Handoko, M Louis</creatorcontrib><creatorcontrib>Van Der Velden, Jolanda</creatorcontrib><creatorcontrib>Noordegraaf, Anton Vonk</creatorcontrib><creatorcontrib>Bogaard, Harm Jan</creatorcontrib><creatorcontrib>Goumans, Marie-José</creatorcontrib><creatorcontrib>de Man, Frances S</creatorcontrib><title>Bone Morphogenetic Protein Receptor Type 2 Mutation in Pulmonary Arterial Hypertension: A View on the Right Ventricle</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>BACKGROUND—The effect of a mutation in the bone morphogenetic protein receptor 2 gene (BMPR2) gene on right ventricular (RV) pressure overload in patients with pulmonary arterial hypertension (PAH) is unknown. Therefore, we investigated RV function in PAH-patients with and without BMPR2 mutation by combining in vivo measurements with molecular and histological analysis of human RV and left ventricular (LV) tissue.
METHODS AND RESULTS—In total, 95 idiopathic or familial PAH patients were genetically screened for the presence of a BMPR2 mutation28 patients had a BMPR2 mutation, 67 patients did not have a BMPR2 mutation. In vivo measurements were assessed using right heart catheterization (RHC) and cardiac magnetic resonance imaging. Despite a similar mean pulmonary artery pressure (non-carriers 54±15 vs. mutation carriers 55±9 mmHg) and pulmonary vascular resistance (755 (483-1043) vs. 931 (624-1311) dynes*s/cm), mutation carriers presented with a more severely compromised RV function (RV ejection fraction37.6±12.8 vs. 29.0±9 %p<0.05, cardiac index 2.7±0.9 vs. 2.2±0.4 l/min/m). Differences continued to exist after treatment. To investigate the role of TGF-β and BMPRII signaling, human RV and LV tissue were studied in controls (n=6), mutation carriers (n=5) and non-carriers (n=11). However, TGF-β and BMPRII signaling, as well as hypertrophy, apoptosis, fibrosis, capillary density, inflammation and cardiac metabolism were similar between mutation carriers and non-carriers.
CONCLUSIONS—Despite a similar afterload, RV function is more severely affected in mutation carriers compared to non-carriers. However, these differences cannot be explained by a differential TGF-β, BMPRII signaling or cardiac adaptation.</description><subject>Adult</subject><subject>Aged</subject><subject>Bone Morphogenetic Protein Receptors, Type II - genetics</subject><subject>Female</subject><subject>Humans</subject><subject>Hypertension, Pulmonary - diagnosis</subject><subject>Hypertension, Pulmonary - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation - genetics</subject><subject>Retrospective Studies</subject><subject>Ventricular Dysfunction, Right - diagnosis</subject><subject>Ventricular Dysfunction, Right - genetics</subject><subject>Ventricular Function, Right - genetics</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE1PxCAQhonR6PrxFwzevFShLRRMPNSNupusH9msXpu2O7UoWyrQbPz3YlZNvHkChuedyTwInVByRimn5-PpfPw0yxfTh_t8kocaOyMx4ZJvoRFlcRqlLJHbaEQIkVGWxPEe2nfuNTx5krFdtBdzKVKZiBEarkwH-M7YvjUv0IFXNX60xoPq8Bxq6L2xePHRA47x3eBLr0yHw9_joFemK-0Hzq0Hq0qNJ4EK984F5ALn-FnBGgfat4Dn6qX1-Bk6b1Wt4RDtNKV2cPR9HqCnm-vFeBLNHm6n43wW1QllPGIpCF7FnAoBNJZ12tCUQt0wymXD0oyxjJKKQbkkvKkoEYxXFSNLASRplixJDtDppm9vzfsAzhcr5WrQuuzADK6gmchCSggZULlBa2ucs9AUvVWrsGBBSfFlvfhrPdRYsbEessffY4ZqBcvf5I_mAFxugLXRwZZ708MabNFCqX37jwGfpzSTFA</recordid><startdate>20160503</startdate><enddate>20160503</enddate><creator>Van Der Bruggen, Cathelijne E.E</creator><creator>Happé, Chris M</creator><creator>Dorfmuller, Peter</creator><creator>Trip, Pia</creator><creator>Spruijt, Onno A</creator><creator>Rol, Nina</creator><creator>Hoevenaars, Femke P</creator><creator>Houweling, Arjan C</creator><creator>Girerd, Barbara</creator><creator>Marcus, Johannes T</creator><creator>Mercier, Olaf</creator><creator>Humbert, Marc</creator><creator>Handoko, M Louis</creator><creator>Van Der Velden, Jolanda</creator><creator>Noordegraaf, Anton Vonk</creator><creator>Bogaard, Harm Jan</creator><creator>Goumans, Marie-José</creator><creator>de Man, Frances S</creator><general>by the American College of Cardiology Foundation and the American Heart Association, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20160503</creationdate><title>Bone Morphogenetic Protein Receptor Type 2 Mutation in Pulmonary Arterial Hypertension: A View on the Right Ventricle</title><author>Van Der Bruggen, Cathelijne E.E ; Happé, Chris M ; Dorfmuller, Peter ; Trip, Pia ; Spruijt, Onno A ; Rol, Nina ; Hoevenaars, Femke P ; Houweling, Arjan C ; Girerd, Barbara ; Marcus, Johannes T ; Mercier, Olaf ; Humbert, Marc ; Handoko, M Louis ; Van Der Velden, Jolanda ; Noordegraaf, Anton Vonk ; Bogaard, Harm Jan ; Goumans, Marie-José ; de Man, Frances S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3156-54e86b26188e129c4f141ecf5169f54755710b5ead06fb10856bb50d8e03fd533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Bone Morphogenetic Protein Receptors, Type II - genetics</topic><topic>Female</topic><topic>Humans</topic><topic>Hypertension, Pulmonary - diagnosis</topic><topic>Hypertension, Pulmonary - genetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation - genetics</topic><topic>Retrospective Studies</topic><topic>Ventricular Dysfunction, Right - diagnosis</topic><topic>Ventricular Dysfunction, Right - genetics</topic><topic>Ventricular Function, Right - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Van Der Bruggen, Cathelijne E.E</creatorcontrib><creatorcontrib>Happé, Chris M</creatorcontrib><creatorcontrib>Dorfmuller, Peter</creatorcontrib><creatorcontrib>Trip, Pia</creatorcontrib><creatorcontrib>Spruijt, Onno A</creatorcontrib><creatorcontrib>Rol, Nina</creatorcontrib><creatorcontrib>Hoevenaars, Femke P</creatorcontrib><creatorcontrib>Houweling, Arjan C</creatorcontrib><creatorcontrib>Girerd, Barbara</creatorcontrib><creatorcontrib>Marcus, Johannes T</creatorcontrib><creatorcontrib>Mercier, Olaf</creatorcontrib><creatorcontrib>Humbert, Marc</creatorcontrib><creatorcontrib>Handoko, M Louis</creatorcontrib><creatorcontrib>Van Der Velden, Jolanda</creatorcontrib><creatorcontrib>Noordegraaf, Anton Vonk</creatorcontrib><creatorcontrib>Bogaard, Harm Jan</creatorcontrib><creatorcontrib>Goumans, Marie-José</creatorcontrib><creatorcontrib>de Man, Frances S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Van Der Bruggen, Cathelijne E.E</au><au>Happé, Chris M</au><au>Dorfmuller, Peter</au><au>Trip, Pia</au><au>Spruijt, Onno A</au><au>Rol, Nina</au><au>Hoevenaars, Femke P</au><au>Houweling, Arjan C</au><au>Girerd, Barbara</au><au>Marcus, Johannes T</au><au>Mercier, Olaf</au><au>Humbert, Marc</au><au>Handoko, M Louis</au><au>Van Der Velden, Jolanda</au><au>Noordegraaf, Anton Vonk</au><au>Bogaard, Harm Jan</au><au>Goumans, Marie-José</au><au>de Man, Frances S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bone Morphogenetic Protein Receptor Type 2 Mutation in Pulmonary Arterial Hypertension: A View on the Right Ventricle</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2016-05-03</date><risdate>2016</risdate><volume>133</volume><issue>18</issue><spage>1747</spage><epage>1760</epage><pages>1747-1760</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><abstract>BACKGROUND—The effect of a mutation in the bone morphogenetic protein receptor 2 gene (BMPR2) gene on right ventricular (RV) pressure overload in patients with pulmonary arterial hypertension (PAH) is unknown. Therefore, we investigated RV function in PAH-patients with and without BMPR2 mutation by combining in vivo measurements with molecular and histological analysis of human RV and left ventricular (LV) tissue.
METHODS AND RESULTS—In total, 95 idiopathic or familial PAH patients were genetically screened for the presence of a BMPR2 mutation28 patients had a BMPR2 mutation, 67 patients did not have a BMPR2 mutation. In vivo measurements were assessed using right heart catheterization (RHC) and cardiac magnetic resonance imaging. Despite a similar mean pulmonary artery pressure (non-carriers 54±15 vs. mutation carriers 55±9 mmHg) and pulmonary vascular resistance (755 (483-1043) vs. 931 (624-1311) dynes*s/cm), mutation carriers presented with a more severely compromised RV function (RV ejection fraction37.6±12.8 vs. 29.0±9 %p<0.05, cardiac index 2.7±0.9 vs. 2.2±0.4 l/min/m). Differences continued to exist after treatment. To investigate the role of TGF-β and BMPRII signaling, human RV and LV tissue were studied in controls (n=6), mutation carriers (n=5) and non-carriers (n=11). However, TGF-β and BMPRII signaling, as well as hypertrophy, apoptosis, fibrosis, capillary density, inflammation and cardiac metabolism were similar between mutation carriers and non-carriers.
CONCLUSIONS—Despite a similar afterload, RV function is more severely affected in mutation carriers compared to non-carriers. However, these differences cannot be explained by a differential TGF-β, BMPRII signaling or cardiac adaptation.</abstract><cop>United States</cop><pub>by the American College of Cardiology Foundation and the American Heart Association, Inc</pub><pmid>26984938</pmid><doi>10.1161/CIRCULATIONAHA.115.020696</doi><tpages>14</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-7322 |
| ispartof | Circulation (New York, N.Y.), 2016-05, Vol.133 (18), p.1747-1760 |
| issn | 0009-7322 1524-4539 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1787085889 |
| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Adult Aged Bone Morphogenetic Protein Receptors, Type II - genetics Female Humans Hypertension, Pulmonary - diagnosis Hypertension, Pulmonary - genetics Male Middle Aged Mutation - genetics Retrospective Studies Ventricular Dysfunction, Right - diagnosis Ventricular Dysfunction, Right - genetics Ventricular Function, Right - genetics |
| title | Bone Morphogenetic Protein Receptor Type 2 Mutation in Pulmonary Arterial Hypertension: A View on the Right Ventricle |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T16%3A34%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Bone%20Morphogenetic%20Protein%20Receptor%20Type%202%20Mutation%20in%20Pulmonary%20Arterial%20Hypertension:%20A%20View%20on%20the%20Right%20Ventricle&rft.jtitle=Circulation%20(New%20York,%20N.Y.)&rft.au=Van%20Der%20Bruggen,%20Cathelijne%20E.E&rft.date=2016-05-03&rft.volume=133&rft.issue=18&rft.spage=1747&rft.epage=1760&rft.pages=1747-1760&rft.issn=0009-7322&rft.eissn=1524-4539&rft_id=info:doi/10.1161/CIRCULATIONAHA.115.020696&rft_dat=%3Cproquest_cross%3E1787085889%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1787085889&rft_id=info:pmid/26984938&rfr_iscdi=true |