Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension
Primary pulmonary hypertension is a progressive and often fatal disorder in humans that results from an increase in pulmonary blood pressure associated with abnormal vascular proliferation. Dexfenfluramine increases the risk of pulmonary hypertension in humans, and its active metabolite is a selecti...
Gespeichert in:
| Veröffentlicht in: | Nature Medicine 2002-10, Vol.8 (10), p.1129-1135 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1135 |
|---|---|
| container_issue | 10 |
| container_start_page | 1129 |
| container_title | Nature Medicine |
| container_volume | 8 |
| creator | Launay, J.-M. Hervé, P. Peoc'h, K. Tournois, C. Callebert, J. Nebigil, C.G. Etienne, N. Drouet, L. Humbert, M. Simonneau, G. Maroteaux, L. |
| description | Primary pulmonary hypertension is a progressive and often fatal disorder in humans that results from an increase in pulmonary blood pressure associated with abnormal vascular proliferation. Dexfenfluramine increases the risk of pulmonary hypertension in humans, and its active metabolite is a selective serotonin 5-hydroxytryptamine 2B (5-HT
2B
) receptor agonist. Thus, we investigated the contribution of the 5-HT
2B
receptor to the pathogenesis of pulmonary hypertension. Using the chronic-hypoxic-mouse model of pulmonary hypertension, we found that the hypoxia-dependent increase in pulmonary blood pressure and lung remodeling are associated with an increase in vascular proliferation, elastase activity and transforming growth factor-β levels, and that these parameters are potentiated by dexfenfluramine treatment. In contrast, hypoxic mice with genetically or pharmacologically inactive 5-HT
2B
receptors manifested no change in any of these parameters. In both humans and mice, pulmonary hypertension is associated with a substantial increase in 5-HT
2B
receptor expression in pulmonary arteries. These data show that activation of 5-HT
2B
receptors is a limiting step in the development of pulmonary hypertension. |
| doi_str_mv | 10.1038/nm764 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_01985063v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A193464138</galeid><sourcerecordid>A193464138</sourcerecordid><originalsourceid>FETCH-LOGICAL-c638t-512302949b3b3c2c707556f7682b34342a446a7f484cba61daa416f80a36e7b33</originalsourceid><addsrcrecordid>eNqN0luL1DAUAOAiintx_4IUwYV96Jp72sdxcS8wsOCq-BbSzOm0S5vUJJXtvzfjDI4j-yB5SDj5cpIcTpadYXSJES0_2EEK9iI7xpyJAkv0_WVaI1kWZcXFUXYSwiNCiCJevc6OMCGMUcSOs4fryZrYOZu7Jo8t5AG8i852NudFO6-8e5qjn8eoh85CTj7mHgyM0fk8kXHqB2e1n_N2HsFHsCGlepO9anQf4Gw3n2Zfrz99ubotlvc3d1eLZWEELWPBMaGIVKyqaU0NMRJJzkUjRUlqyigjmjGhZcNKZmot8EprhkVTIk0FyJrS0-xim7fVvRp9N6SHKKc7dbtYqk0M4arkSNCfONnzrR29-zFBiGrogoG-1xbcFJQkmGGOZYLv_oGPbvI2_UMRQjHmEm-yFVu01j2ozjYuem3WYMHr3llouhRe4IoywTAtk798xqexgqEzzx64ODiQTISnuNZTCOru4fP_2_tvh_b8L9uC7mMbXD9tOiAcwvdbaLwLwUPzp8AYqU3Dqd8Nl9zbXbmmeoDVXu06bH9jSFt2DX5fz8NMvwBsC9eC</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>223115711</pqid></control><display><type>article</type><title>Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>Nature Journals Online</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Launay, J.-M. ; Hervé, P. ; Peoc'h, K. ; Tournois, C. ; Callebert, J. ; Nebigil, C.G. ; Etienne, N. ; Drouet, L. ; Humbert, M. ; Simonneau, G. ; Maroteaux, L.</creator><creatorcontrib>Launay, J.-M. ; Hervé, P. ; Peoc'h, K. ; Tournois, C. ; Callebert, J. ; Nebigil, C.G. ; Etienne, N. ; Drouet, L. ; Humbert, M. ; Simonneau, G. ; Maroteaux, L.</creatorcontrib><description>Primary pulmonary hypertension is a progressive and often fatal disorder in humans that results from an increase in pulmonary blood pressure associated with abnormal vascular proliferation. Dexfenfluramine increases the risk of pulmonary hypertension in humans, and its active metabolite is a selective serotonin 5-hydroxytryptamine 2B (5-HT
2B
) receptor agonist. Thus, we investigated the contribution of the 5-HT
2B
receptor to the pathogenesis of pulmonary hypertension. Using the chronic-hypoxic-mouse model of pulmonary hypertension, we found that the hypoxia-dependent increase in pulmonary blood pressure and lung remodeling are associated with an increase in vascular proliferation, elastase activity and transforming growth factor-β levels, and that these parameters are potentiated by dexfenfluramine treatment. In contrast, hypoxic mice with genetically or pharmacologically inactive 5-HT
2B
receptors manifested no change in any of these parameters. In both humans and mice, pulmonary hypertension is associated with a substantial increase in 5-HT
2B
receptor expression in pulmonary arteries. These data show that activation of 5-HT
2B
receptors is a limiting step in the development of pulmonary hypertension.</description><identifier>ISSN: 1078-8956</identifier><identifier>EISSN: 1546-170X</identifier><identifier>EISSN: 1744-7933</identifier><identifier>DOI: 10.1038/nm764</identifier><identifier>PMID: 12244304</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Animals ; Biochemistry, Molecular Biology ; Biomedical and Life Sciences ; Biomedicine ; Blood Pressure ; Cancer Research ; Cell Division ; Dexfenfluramine ; Dexfenfluramine - metabolism ; Dexfenfluramine - pharmacology ; Disease Models, Animal ; DNA ; DNA - biosynthesis ; Female ; Human health and pathology ; Humans ; Hypertension ; Hypertension, Pulmonary ; Hypertension, Pulmonary - metabolism ; Hypertension, Pulmonary - pathology ; Hypoxia ; Hypoxia - physiopathology ; Infectious Diseases ; Kinases ; Life Sciences ; Ligands ; Lung ; Lung - blood supply ; Lung - metabolism ; Lung - pathology ; Male ; Metabolic Diseases ; Metabolites ; Mice ; Molecular Medicine ; Neurosciences ; Organ Culture Techniques ; Pulmonary arteries ; Pulmonary Artery ; Pulmonary Artery - metabolism ; Pulmonary Artery - pathology ; Pulmonary hypertension ; Pulmonology and respiratory tract ; Pyrimidines ; Pyrimidines - pharmacology ; Receptor, Serotonin, 5-HT2B ; Receptors, Serotonin ; Receptors, Serotonin - genetics ; Receptors, Serotonin - metabolism ; Serotonin ; Serotonin - metabolism ; Serotonin Antagonists ; Serotonin Antagonists - metabolism ; Serotonin Receptor Agonists ; Serotonin Receptor Agonists - pharmacology ; Vasoconstriction ; Veins & arteries</subject><ispartof>Nature Medicine, 2002-10, Vol.8 (10), p.1129-1135</ispartof><rights>Springer Nature America, Inc. 2002</rights><rights>COPYRIGHT 2002 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Oct 2002</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c638t-512302949b3b3c2c707556f7682b34342a446a7f484cba61daa416f80a36e7b33</citedby><cites>FETCH-LOGICAL-c638t-512302949b3b3c2c707556f7682b34342a446a7f484cba61daa416f80a36e7b33</cites><orcidid>0000-0002-9499-8603 ; 0000-0002-2035-5795</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nm764$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nm764$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12244304$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01985063$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Launay, J.-M.</creatorcontrib><creatorcontrib>Hervé, P.</creatorcontrib><creatorcontrib>Peoc'h, K.</creatorcontrib><creatorcontrib>Tournois, C.</creatorcontrib><creatorcontrib>Callebert, J.</creatorcontrib><creatorcontrib>Nebigil, C.G.</creatorcontrib><creatorcontrib>Etienne, N.</creatorcontrib><creatorcontrib>Drouet, L.</creatorcontrib><creatorcontrib>Humbert, M.</creatorcontrib><creatorcontrib>Simonneau, G.</creatorcontrib><creatorcontrib>Maroteaux, L.</creatorcontrib><title>Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension</title><title>Nature Medicine</title><addtitle>Nat Med</addtitle><addtitle>Nat Med</addtitle><description>Primary pulmonary hypertension is a progressive and often fatal disorder in humans that results from an increase in pulmonary blood pressure associated with abnormal vascular proliferation. Dexfenfluramine increases the risk of pulmonary hypertension in humans, and its active metabolite is a selective serotonin 5-hydroxytryptamine 2B (5-HT
2B
) receptor agonist. Thus, we investigated the contribution of the 5-HT
2B
receptor to the pathogenesis of pulmonary hypertension. Using the chronic-hypoxic-mouse model of pulmonary hypertension, we found that the hypoxia-dependent increase in pulmonary blood pressure and lung remodeling are associated with an increase in vascular proliferation, elastase activity and transforming growth factor-β levels, and that these parameters are potentiated by dexfenfluramine treatment. In contrast, hypoxic mice with genetically or pharmacologically inactive 5-HT
2B
receptors manifested no change in any of these parameters. In both humans and mice, pulmonary hypertension is associated with a substantial increase in 5-HT
2B
receptor expression in pulmonary arteries. These data show that activation of 5-HT
2B
receptors is a limiting step in the development of pulmonary hypertension.</description><subject>Animals</subject><subject>Biochemistry, Molecular Biology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood Pressure</subject><subject>Cancer Research</subject><subject>Cell Division</subject><subject>Dexfenfluramine</subject><subject>Dexfenfluramine - metabolism</subject><subject>Dexfenfluramine - pharmacology</subject><subject>Disease Models, Animal</subject><subject>DNA</subject><subject>DNA - biosynthesis</subject><subject>Female</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypertension, Pulmonary</subject><subject>Hypertension, Pulmonary - metabolism</subject><subject>Hypertension, Pulmonary - pathology</subject><subject>Hypoxia</subject><subject>Hypoxia - physiopathology</subject><subject>Infectious Diseases</subject><subject>Kinases</subject><subject>Life Sciences</subject><subject>Ligands</subject><subject>Lung</subject><subject>Lung - blood supply</subject><subject>Lung - metabolism</subject><subject>Lung - pathology</subject><subject>Male</subject><subject>Metabolic Diseases</subject><subject>Metabolites</subject><subject>Mice</subject><subject>Molecular Medicine</subject><subject>Neurosciences</subject><subject>Organ Culture Techniques</subject><subject>Pulmonary arteries</subject><subject>Pulmonary Artery</subject><subject>Pulmonary Artery - metabolism</subject><subject>Pulmonary Artery - pathology</subject><subject>Pulmonary hypertension</subject><subject>Pulmonology and respiratory tract</subject><subject>Pyrimidines</subject><subject>Pyrimidines - pharmacology</subject><subject>Receptor, Serotonin, 5-HT2B</subject><subject>Receptors, Serotonin</subject><subject>Receptors, Serotonin - genetics</subject><subject>Receptors, Serotonin - metabolism</subject><subject>Serotonin</subject><subject>Serotonin - metabolism</subject><subject>Serotonin Antagonists</subject><subject>Serotonin Antagonists - metabolism</subject><subject>Serotonin Receptor Agonists</subject><subject>Serotonin Receptor Agonists - pharmacology</subject><subject>Vasoconstriction</subject><subject>Veins & arteries</subject><issn>1078-8956</issn><issn>1546-170X</issn><issn>1744-7933</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN0luL1DAUAOAiintx_4IUwYV96Jp72sdxcS8wsOCq-BbSzOm0S5vUJJXtvzfjDI4j-yB5SDj5cpIcTpadYXSJES0_2EEK9iI7xpyJAkv0_WVaI1kWZcXFUXYSwiNCiCJevc6OMCGMUcSOs4fryZrYOZu7Jo8t5AG8i852NudFO6-8e5qjn8eoh85CTj7mHgyM0fk8kXHqB2e1n_N2HsFHsCGlepO9anQf4Gw3n2Zfrz99ubotlvc3d1eLZWEELWPBMaGIVKyqaU0NMRJJzkUjRUlqyigjmjGhZcNKZmot8EprhkVTIk0FyJrS0-xim7fVvRp9N6SHKKc7dbtYqk0M4arkSNCfONnzrR29-zFBiGrogoG-1xbcFJQkmGGOZYLv_oGPbvI2_UMRQjHmEm-yFVu01j2ozjYuem3WYMHr3llouhRe4IoywTAtk798xqexgqEzzx64ODiQTISnuNZTCOru4fP_2_tvh_b8L9uC7mMbXD9tOiAcwvdbaLwLwUPzp8AYqU3Dqd8Nl9zbXbmmeoDVXu06bH9jSFt2DX5fz8NMvwBsC9eC</recordid><startdate>20021001</startdate><enddate>20021001</enddate><creator>Launay, J.-M.</creator><creator>Hervé, P.</creator><creator>Peoc'h, K.</creator><creator>Tournois, C.</creator><creator>Callebert, J.</creator><creator>Nebigil, C.G.</creator><creator>Etienne, N.</creator><creator>Drouet, L.</creator><creator>Humbert, M.</creator><creator>Simonneau, G.</creator><creator>Maroteaux, L.</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0002-9499-8603</orcidid><orcidid>https://orcid.org/0000-0002-2035-5795</orcidid></search><sort><creationdate>20021001</creationdate><title>Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension</title><author>Launay, J.-M. ; Hervé, P. ; Peoc'h, K. ; Tournois, C. ; Callebert, J. ; Nebigil, C.G. ; Etienne, N. ; Drouet, L. ; Humbert, M. ; Simonneau, G. ; Maroteaux, L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c638t-512302949b3b3c2c707556f7682b34342a446a7f484cba61daa416f80a36e7b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Biochemistry, Molecular Biology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blood Pressure</topic><topic>Cancer Research</topic><topic>Cell Division</topic><topic>Dexfenfluramine</topic><topic>Dexfenfluramine - metabolism</topic><topic>Dexfenfluramine - pharmacology</topic><topic>Disease Models, Animal</topic><topic>DNA</topic><topic>DNA - biosynthesis</topic><topic>Female</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypertension, Pulmonary</topic><topic>Hypertension, Pulmonary - metabolism</topic><topic>Hypertension, Pulmonary - pathology</topic><topic>Hypoxia</topic><topic>Hypoxia - physiopathology</topic><topic>Infectious Diseases</topic><topic>Kinases</topic><topic>Life Sciences</topic><topic>Ligands</topic><topic>Lung</topic><topic>Lung - blood supply</topic><topic>Lung - metabolism</topic><topic>Lung - pathology</topic><topic>Male</topic><topic>Metabolic Diseases</topic><topic>Metabolites</topic><topic>Mice</topic><topic>Molecular Medicine</topic><topic>Neurosciences</topic><topic>Organ Culture Techniques</topic><topic>Pulmonary arteries</topic><topic>Pulmonary Artery</topic><topic>Pulmonary Artery - metabolism</topic><topic>Pulmonary Artery - pathology</topic><topic>Pulmonary hypertension</topic><topic>Pulmonology and respiratory tract</topic><topic>Pyrimidines</topic><topic>Pyrimidines - pharmacology</topic><topic>Receptor, Serotonin, 5-HT2B</topic><topic>Receptors, Serotonin</topic><topic>Receptors, Serotonin - genetics</topic><topic>Receptors, Serotonin - metabolism</topic><topic>Serotonin</topic><topic>Serotonin - metabolism</topic><topic>Serotonin Antagonists</topic><topic>Serotonin Antagonists - metabolism</topic><topic>Serotonin Receptor Agonists</topic><topic>Serotonin Receptor Agonists - pharmacology</topic><topic>Vasoconstriction</topic><topic>Veins & arteries</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Launay, J.-M.</creatorcontrib><creatorcontrib>Hervé, P.</creatorcontrib><creatorcontrib>Peoc'h, K.</creatorcontrib><creatorcontrib>Tournois, C.</creatorcontrib><creatorcontrib>Callebert, J.</creatorcontrib><creatorcontrib>Nebigil, C.G.</creatorcontrib><creatorcontrib>Etienne, N.</creatorcontrib><creatorcontrib>Drouet, L.</creatorcontrib><creatorcontrib>Humbert, M.</creatorcontrib><creatorcontrib>Simonneau, G.</creatorcontrib><creatorcontrib>Maroteaux, L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Nature Medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Launay, J.-M.</au><au>Hervé, P.</au><au>Peoc'h, K.</au><au>Tournois, C.</au><au>Callebert, J.</au><au>Nebigil, C.G.</au><au>Etienne, N.</au><au>Drouet, L.</au><au>Humbert, M.</au><au>Simonneau, G.</au><au>Maroteaux, L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension</atitle><jtitle>Nature Medicine</jtitle><stitle>Nat Med</stitle><addtitle>Nat Med</addtitle><date>2002-10-01</date><risdate>2002</risdate><volume>8</volume><issue>10</issue><spage>1129</spage><epage>1135</epage><pages>1129-1135</pages><issn>1078-8956</issn><eissn>1546-170X</eissn><eissn>1744-7933</eissn><abstract>Primary pulmonary hypertension is a progressive and often fatal disorder in humans that results from an increase in pulmonary blood pressure associated with abnormal vascular proliferation. Dexfenfluramine increases the risk of pulmonary hypertension in humans, and its active metabolite is a selective serotonin 5-hydroxytryptamine 2B (5-HT
2B
) receptor agonist. Thus, we investigated the contribution of the 5-HT
2B
receptor to the pathogenesis of pulmonary hypertension. Using the chronic-hypoxic-mouse model of pulmonary hypertension, we found that the hypoxia-dependent increase in pulmonary blood pressure and lung remodeling are associated with an increase in vascular proliferation, elastase activity and transforming growth factor-β levels, and that these parameters are potentiated by dexfenfluramine treatment. In contrast, hypoxic mice with genetically or pharmacologically inactive 5-HT
2B
receptors manifested no change in any of these parameters. In both humans and mice, pulmonary hypertension is associated with a substantial increase in 5-HT
2B
receptor expression in pulmonary arteries. These data show that activation of 5-HT
2B
receptors is a limiting step in the development of pulmonary hypertension.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>12244304</pmid><doi>10.1038/nm764</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-9499-8603</orcidid><orcidid>https://orcid.org/0000-0002-2035-5795</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-8956 |
| ispartof | Nature Medicine, 2002-10, Vol.8 (10), p.1129-1135 |
| issn | 1078-8956 1546-170X 1744-7933 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_01985063v1 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Biochemistry, Molecular Biology Biomedical and Life Sciences Biomedicine Blood Pressure Cancer Research Cell Division Dexfenfluramine Dexfenfluramine - metabolism Dexfenfluramine - pharmacology Disease Models, Animal DNA DNA - biosynthesis Female Human health and pathology Humans Hypertension Hypertension, Pulmonary Hypertension, Pulmonary - metabolism Hypertension, Pulmonary - pathology Hypoxia Hypoxia - physiopathology Infectious Diseases Kinases Life Sciences Ligands Lung Lung - blood supply Lung - metabolism Lung - pathology Male Metabolic Diseases Metabolites Mice Molecular Medicine Neurosciences Organ Culture Techniques Pulmonary arteries Pulmonary Artery Pulmonary Artery - metabolism Pulmonary Artery - pathology Pulmonary hypertension Pulmonology and respiratory tract Pyrimidines Pyrimidines - pharmacology Receptor, Serotonin, 5-HT2B Receptors, Serotonin Receptors, Serotonin - genetics Receptors, Serotonin - metabolism Serotonin Serotonin - metabolism Serotonin Antagonists Serotonin Antagonists - metabolism Serotonin Receptor Agonists Serotonin Receptor Agonists - pharmacology Vasoconstriction Veins & arteries |
| title | Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T11%3A52%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Function%20of%20the%20serotonin%205-hydroxytryptamine%202B%20receptor%20in%20pulmonary%20hypertension&rft.jtitle=Nature%20Medicine&rft.au=Launay,%20J.-M.&rft.date=2002-10-01&rft.volume=8&rft.issue=10&rft.spage=1129&rft.epage=1135&rft.pages=1129-1135&rft.issn=1078-8956&rft.eissn=1546-170X&rft_id=info:doi/10.1038/nm764&rft_dat=%3Cgale_hal_p%3EA193464138%3C/gale_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=223115711&rft_id=info:pmid/12244304&rft_galeid=A193464138&rfr_iscdi=true |