MEF2C silencing attenuates load-induced left ventricular hypertrophy by modulating mTOR/S6K pathway in mice

The activation of the members of the myocyte enhancer factor-2 family (MEF2A, B, C and D) of transcription factors promotes cardiac hypertrophy and failure. However, the role of its individual components in the pathogenesis of cardiac hypertrophy remains unclear. In this study, we investigated wheth...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one 2009-12, Vol.4 (12), p.e8472-e8472
Hauptverfasser: Pereira, Ana Helena M, Clemente, Carolina F M Z, Cardoso, Alisson C, Theizen, Thais H, Rocco, Silvana A, Judice, Carla C, Guido, Maria Carolina, Pascoal, Vinícius D B, Lopes-Cendes, Iscia, Souza, José Roberto M, Franchini, Kleber G
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page e8472
container_issue 12
container_start_page e8472
container_title PloS one
container_volume 4
creator Pereira, Ana Helena M
Clemente, Carolina F M Z
Cardoso, Alisson C
Theizen, Thais H
Rocco, Silvana A
Judice, Carla C
Guido, Maria Carolina
Pascoal, Vinícius D B
Lopes-Cendes, Iscia
Souza, José Roberto M
Franchini, Kleber G
description The activation of the members of the myocyte enhancer factor-2 family (MEF2A, B, C and D) of transcription factors promotes cardiac hypertrophy and failure. However, the role of its individual components in the pathogenesis of cardiac hypertrophy remains unclear. In this study, we investigated whether MEF2C plays a role in mediating the left ventricular hypertrophy by pressure overload in mice. The knockdown of myocardial MEF2C induced by specific small interfering RNA (siRNA) has been shown to attenuate hypertrophy, interstitial fibrosis and the rise of ANP levels in aortic banded mice. We detected that the depletion of MEF2C also results in lowered levels of both PGC-1alpha and mitochondrial DNA in the overloaded left ventricle, associated with enhanced AMP:ATP ratio. Additionally, MEF2C depletion was accompanied by defective activation of S6K in response to pressure overload. Treatment with the amino acid leucine stimulated S6K and suppressed the attenuation of left ventricular hypertrophy and fibrosis in the aforementioned aortic banded mice. These findings represent new evidences that MEF2C depletion attenuates the hypertrophic responses to mechanical stress and highlight the potential of MEF2C to be a target for new therapies to cardiac hypertrophy and failure.
doi_str_mv 10.1371/journal.pone.0008472
format Article
fullrecord <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1292309875</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A472751659</galeid><doaj_id>oai_doaj_org_article_3c8f0d18666843bb96e89875de924440</doaj_id><sourcerecordid>A472751659</sourcerecordid><originalsourceid>FETCH-LOGICAL-c729t-b93a6f1200f318bb0f6a36dfaa3e7b2f1a0dd121ce428c66c147bdb749ab06153</originalsourceid><addsrcrecordid>eNqNkl9v0zAUxSMEYmPwDRBYQgLx0M5_Eid5QZqqDSqGJm2DV8uxncbFsYPtDPrtcWg3tYgHlAdH9u8eX597suwlgnNESnS6dqO33MwHZ9UcQljlJX6UHaOa4BnFkDze-z_KnoWwhrAgFaVPsyMMYY5QgY-z71_OL_ACBG2UFdquAI9R2ZFHFYBxXM60laNQEhjVRnCnbPRajIZ70G0G5aN3Q7cBzQb0TqbtOEn0t1fXpzf0Mxh47H7yDdAW9Fqo59mTlpugXuzWk-zrxfnt4tPs8urjcnF2ORMlruOsqQmnLUo9tgRVTQNbygmVLedElQ1uEYdSIoyEynElKBUoLxvZlHnNG0hRQU6y11vdwbjAdj4FhnCNCayrciKWW0I6vmaD1z33G-a4Zn82nF8x7qMWRjEiqhZKlHyjVU6apqaqmjSkqnGe5zBpfdjdNja9kmKyiJsD0cMTqzu2cncMl3WeBpIE3u0EvPsxqhBZr4NQxnCr3BhYSdK4CS2mtt_8Rf77cfMtteKpf21bl64V6ZMqTSGlpU3DZmcpLmWBaFGngvcHBYmJ6ldc8TEEtry5_n_26tsh-3aP7RQ3sQvOjFE7Gw7BfAsK70Lwqn1wD0E2hf3-nWwKO9uFPZW92nf-oeg-3eQ3DCD6sQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1292309875</pqid></control><display><type>article</type><title>MEF2C silencing attenuates load-induced left ventricular hypertrophy by modulating mTOR/S6K pathway in mice</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Pereira, Ana Helena M ; Clemente, Carolina F M Z ; Cardoso, Alisson C ; Theizen, Thais H ; Rocco, Silvana A ; Judice, Carla C ; Guido, Maria Carolina ; Pascoal, Vinícius D B ; Lopes-Cendes, Iscia ; Souza, José Roberto M ; Franchini, Kleber G</creator><contributor>Schwartz, Arnold</contributor><creatorcontrib>Pereira, Ana Helena M ; Clemente, Carolina F M Z ; Cardoso, Alisson C ; Theizen, Thais H ; Rocco, Silvana A ; Judice, Carla C ; Guido, Maria Carolina ; Pascoal, Vinícius D B ; Lopes-Cendes, Iscia ; Souza, José Roberto M ; Franchini, Kleber G ; Schwartz, Arnold</creatorcontrib><description>The activation of the members of the myocyte enhancer factor-2 family (MEF2A, B, C and D) of transcription factors promotes cardiac hypertrophy and failure. However, the role of its individual components in the pathogenesis of cardiac hypertrophy remains unclear. In this study, we investigated whether MEF2C plays a role in mediating the left ventricular hypertrophy by pressure overload in mice. The knockdown of myocardial MEF2C induced by specific small interfering RNA (siRNA) has been shown to attenuate hypertrophy, interstitial fibrosis and the rise of ANP levels in aortic banded mice. We detected that the depletion of MEF2C also results in lowered levels of both PGC-1alpha and mitochondrial DNA in the overloaded left ventricle, associated with enhanced AMP:ATP ratio. Additionally, MEF2C depletion was accompanied by defective activation of S6K in response to pressure overload. Treatment with the amino acid leucine stimulated S6K and suppressed the attenuation of left ventricular hypertrophy and fibrosis in the aforementioned aortic banded mice. These findings represent new evidences that MEF2C depletion attenuates the hypertrophic responses to mechanical stress and highlight the potential of MEF2C to be a target for new therapies to cardiac hypertrophy and failure.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0008472</identifier><identifier>PMID: 20041152</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Amino acids ; AMP ; Animals ; Aorta ; Atherosclerosis ; Attenuation ; Biochemistry/Cell Signaling and Trafficking Structures ; Biochemistry/Transcription and Translation ; Biosynthesis ; Cardiomyocytes ; Cardiomyopathy ; Cardiovascular Disorders/Heart Failure ; Cell Biology/Cell Growth and Division ; Cell growth ; Cells, Cultured ; Deoxyribonucleic acid ; Depletion ; DNA ; DNA binding proteins ; DNA, Mitochondrial - genetics ; Fibrosis ; Gene Silencing ; Heart ; Heart diseases ; Heart failure ; Heart hypertrophy ; Hemodynamics ; Hypertrophy ; Hypertrophy, Left Ventricular - enzymology ; Hypertrophy, Left Ventricular - physiopathology ; Internal medicine ; Intracellular Signaling Peptides and Proteins - metabolism ; Kinases ; Leucine ; Medicine ; MEF2 Transcription Factors ; Mice ; Mitochondrial DNA ; Myocardium - enzymology ; Myocardium - pathology ; Myocytes, Cardiac - metabolism ; Myocytes, Cardiac - pathology ; Myogenic Regulatory Factors - genetics ; Myogenic Regulatory Factors - metabolism ; Pathogenesis ; Pressure ; Protein expression ; Protein synthesis ; Protein-Serine-Threonine Kinases - metabolism ; Proteins ; Rats ; Ribonucleic acid ; Ribosomal Protein S6 Kinases, 90-kDa - metabolism ; RNA ; RNA, Small Interfering - metabolism ; Rodents ; Signal Transduction ; siRNA ; Stem cells ; TOR protein ; TOR Serine-Threonine Kinases ; Transcription factors ; Ventricle ; Ventricular Pressure - physiology</subject><ispartof>PloS one, 2009-12, Vol.4 (12), p.e8472-e8472</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>2009 Pereira et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Pereira et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c729t-b93a6f1200f318bb0f6a36dfaa3e7b2f1a0dd121ce428c66c147bdb749ab06153</citedby><cites>FETCH-LOGICAL-c729t-b93a6f1200f318bb0f6a36dfaa3e7b2f1a0dd121ce428c66c147bdb749ab06153</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794538/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794538/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20041152$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Schwartz, Arnold</contributor><creatorcontrib>Pereira, Ana Helena M</creatorcontrib><creatorcontrib>Clemente, Carolina F M Z</creatorcontrib><creatorcontrib>Cardoso, Alisson C</creatorcontrib><creatorcontrib>Theizen, Thais H</creatorcontrib><creatorcontrib>Rocco, Silvana A</creatorcontrib><creatorcontrib>Judice, Carla C</creatorcontrib><creatorcontrib>Guido, Maria Carolina</creatorcontrib><creatorcontrib>Pascoal, Vinícius D B</creatorcontrib><creatorcontrib>Lopes-Cendes, Iscia</creatorcontrib><creatorcontrib>Souza, José Roberto M</creatorcontrib><creatorcontrib>Franchini, Kleber G</creatorcontrib><title>MEF2C silencing attenuates load-induced left ventricular hypertrophy by modulating mTOR/S6K pathway in mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The activation of the members of the myocyte enhancer factor-2 family (MEF2A, B, C and D) of transcription factors promotes cardiac hypertrophy and failure. However, the role of its individual components in the pathogenesis of cardiac hypertrophy remains unclear. In this study, we investigated whether MEF2C plays a role in mediating the left ventricular hypertrophy by pressure overload in mice. The knockdown of myocardial MEF2C induced by specific small interfering RNA (siRNA) has been shown to attenuate hypertrophy, interstitial fibrosis and the rise of ANP levels in aortic banded mice. We detected that the depletion of MEF2C also results in lowered levels of both PGC-1alpha and mitochondrial DNA in the overloaded left ventricle, associated with enhanced AMP:ATP ratio. Additionally, MEF2C depletion was accompanied by defective activation of S6K in response to pressure overload. Treatment with the amino acid leucine stimulated S6K and suppressed the attenuation of left ventricular hypertrophy and fibrosis in the aforementioned aortic banded mice. These findings represent new evidences that MEF2C depletion attenuates the hypertrophic responses to mechanical stress and highlight the potential of MEF2C to be a target for new therapies to cardiac hypertrophy and failure.</description><subject>Activation</subject><subject>Amino acids</subject><subject>AMP</subject><subject>Animals</subject><subject>Aorta</subject><subject>Atherosclerosis</subject><subject>Attenuation</subject><subject>Biochemistry/Cell Signaling and Trafficking Structures</subject><subject>Biochemistry/Transcription and Translation</subject><subject>Biosynthesis</subject><subject>Cardiomyocytes</subject><subject>Cardiomyopathy</subject><subject>Cardiovascular Disorders/Heart Failure</subject><subject>Cell Biology/Cell Growth and Division</subject><subject>Cell growth</subject><subject>Cells, Cultured</subject><subject>Deoxyribonucleic acid</subject><subject>Depletion</subject><subject>DNA</subject><subject>DNA binding proteins</subject><subject>DNA, Mitochondrial - genetics</subject><subject>Fibrosis</subject><subject>Gene Silencing</subject><subject>Heart</subject><subject>Heart diseases</subject><subject>Heart failure</subject><subject>Heart hypertrophy</subject><subject>Hemodynamics</subject><subject>Hypertrophy</subject><subject>Hypertrophy, Left Ventricular - enzymology</subject><subject>Hypertrophy, Left Ventricular - physiopathology</subject><subject>Internal medicine</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Kinases</subject><subject>Leucine</subject><subject>Medicine</subject><subject>MEF2 Transcription Factors</subject><subject>Mice</subject><subject>Mitochondrial DNA</subject><subject>Myocardium - enzymology</subject><subject>Myocardium - pathology</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Myocytes, Cardiac - pathology</subject><subject>Myogenic Regulatory Factors - genetics</subject><subject>Myogenic Regulatory Factors - metabolism</subject><subject>Pathogenesis</subject><subject>Pressure</subject><subject>Protein expression</subject><subject>Protein synthesis</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proteins</subject><subject>Rats</subject><subject>Ribonucleic acid</subject><subject>Ribosomal Protein S6 Kinases, 90-kDa - metabolism</subject><subject>RNA</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>siRNA</subject><subject>Stem cells</subject><subject>TOR protein</subject><subject>TOR Serine-Threonine Kinases</subject><subject>Transcription factors</subject><subject>Ventricle</subject><subject>Ventricular Pressure - physiology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl9v0zAUxSMEYmPwDRBYQgLx0M5_Eid5QZqqDSqGJm2DV8uxncbFsYPtDPrtcWg3tYgHlAdH9u8eX597suwlgnNESnS6dqO33MwHZ9UcQljlJX6UHaOa4BnFkDze-z_KnoWwhrAgFaVPsyMMYY5QgY-z71_OL_ACBG2UFdquAI9R2ZFHFYBxXM60laNQEhjVRnCnbPRajIZ70G0G5aN3Q7cBzQb0TqbtOEn0t1fXpzf0Mxh47H7yDdAW9Fqo59mTlpugXuzWk-zrxfnt4tPs8urjcnF2ORMlruOsqQmnLUo9tgRVTQNbygmVLedElQ1uEYdSIoyEynElKBUoLxvZlHnNG0hRQU6y11vdwbjAdj4FhnCNCayrciKWW0I6vmaD1z33G-a4Zn82nF8x7qMWRjEiqhZKlHyjVU6apqaqmjSkqnGe5zBpfdjdNja9kmKyiJsD0cMTqzu2cncMl3WeBpIE3u0EvPsxqhBZr4NQxnCr3BhYSdK4CS2mtt_8Rf77cfMtteKpf21bl64V6ZMqTSGlpU3DZmcpLmWBaFGngvcHBYmJ6ldc8TEEtry5_n_26tsh-3aP7RQ3sQvOjFE7Gw7BfAsK70Lwqn1wD0E2hf3-nWwKO9uFPZW92nf-oeg-3eQ3DCD6sQ</recordid><startdate>20091229</startdate><enddate>20091229</enddate><creator>Pereira, Ana Helena M</creator><creator>Clemente, Carolina F M Z</creator><creator>Cardoso, Alisson C</creator><creator>Theizen, Thais H</creator><creator>Rocco, Silvana A</creator><creator>Judice, Carla C</creator><creator>Guido, Maria Carolina</creator><creator>Pascoal, Vinícius D B</creator><creator>Lopes-Cendes, Iscia</creator><creator>Souza, José Roberto M</creator><creator>Franchini, Kleber G</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20091229</creationdate><title>MEF2C silencing attenuates load-induced left ventricular hypertrophy by modulating mTOR/S6K pathway in mice</title><author>Pereira, Ana Helena M ; Clemente, Carolina F M Z ; Cardoso, Alisson C ; Theizen, Thais H ; Rocco, Silvana A ; Judice, Carla C ; Guido, Maria Carolina ; Pascoal, Vinícius D B ; Lopes-Cendes, Iscia ; Souza, José Roberto M ; Franchini, Kleber G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c729t-b93a6f1200f318bb0f6a36dfaa3e7b2f1a0dd121ce428c66c147bdb749ab06153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Activation</topic><topic>Amino acids</topic><topic>AMP</topic><topic>Animals</topic><topic>Aorta</topic><topic>Atherosclerosis</topic><topic>Attenuation</topic><topic>Biochemistry/Cell Signaling and Trafficking Structures</topic><topic>Biochemistry/Transcription and Translation</topic><topic>Biosynthesis</topic><topic>Cardiomyocytes</topic><topic>Cardiomyopathy</topic><topic>Cardiovascular Disorders/Heart Failure</topic><topic>Cell Biology/Cell Growth and Division</topic><topic>Cell growth</topic><topic>Cells, Cultured</topic><topic>Deoxyribonucleic acid</topic><topic>Depletion</topic><topic>DNA</topic><topic>DNA binding proteins</topic><topic>DNA, Mitochondrial - genetics</topic><topic>Fibrosis</topic><topic>Gene Silencing</topic><topic>Heart</topic><topic>Heart diseases</topic><topic>Heart failure</topic><topic>Heart hypertrophy</topic><topic>Hemodynamics</topic><topic>Hypertrophy</topic><topic>Hypertrophy, Left Ventricular - enzymology</topic><topic>Hypertrophy, Left Ventricular - physiopathology</topic><topic>Internal medicine</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Kinases</topic><topic>Leucine</topic><topic>Medicine</topic><topic>MEF2 Transcription Factors</topic><topic>Mice</topic><topic>Mitochondrial DNA</topic><topic>Myocardium - enzymology</topic><topic>Myocardium - pathology</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Myocytes, Cardiac - pathology</topic><topic>Myogenic Regulatory Factors - genetics</topic><topic>Myogenic Regulatory Factors - metabolism</topic><topic>Pathogenesis</topic><topic>Pressure</topic><topic>Protein expression</topic><topic>Protein synthesis</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Proteins</topic><topic>Rats</topic><topic>Ribonucleic acid</topic><topic>Ribosomal Protein S6 Kinases, 90-kDa - metabolism</topic><topic>RNA</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Rodents</topic><topic>Signal Transduction</topic><topic>siRNA</topic><topic>Stem cells</topic><topic>TOR protein</topic><topic>TOR Serine-Threonine Kinases</topic><topic>Transcription factors</topic><topic>Ventricle</topic><topic>Ventricular Pressure - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pereira, Ana Helena M</creatorcontrib><creatorcontrib>Clemente, Carolina F M Z</creatorcontrib><creatorcontrib>Cardoso, Alisson C</creatorcontrib><creatorcontrib>Theizen, Thais H</creatorcontrib><creatorcontrib>Rocco, Silvana A</creatorcontrib><creatorcontrib>Judice, Carla C</creatorcontrib><creatorcontrib>Guido, Maria Carolina</creatorcontrib><creatorcontrib>Pascoal, Vinícius D B</creatorcontrib><creatorcontrib>Lopes-Cendes, Iscia</creatorcontrib><creatorcontrib>Souza, José Roberto M</creatorcontrib><creatorcontrib>Franchini, Kleber G</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints in Context (Gale)</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing &amp; Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</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>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pereira, Ana Helena M</au><au>Clemente, Carolina F M Z</au><au>Cardoso, Alisson C</au><au>Theizen, Thais H</au><au>Rocco, Silvana A</au><au>Judice, Carla C</au><au>Guido, Maria Carolina</au><au>Pascoal, Vinícius D B</au><au>Lopes-Cendes, Iscia</au><au>Souza, José Roberto M</au><au>Franchini, Kleber G</au><au>Schwartz, Arnold</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MEF2C silencing attenuates load-induced left ventricular hypertrophy by modulating mTOR/S6K pathway in mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2009-12-29</date><risdate>2009</risdate><volume>4</volume><issue>12</issue><spage>e8472</spage><epage>e8472</epage><pages>e8472-e8472</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The activation of the members of the myocyte enhancer factor-2 family (MEF2A, B, C and D) of transcription factors promotes cardiac hypertrophy and failure. However, the role of its individual components in the pathogenesis of cardiac hypertrophy remains unclear. In this study, we investigated whether MEF2C plays a role in mediating the left ventricular hypertrophy by pressure overload in mice. The knockdown of myocardial MEF2C induced by specific small interfering RNA (siRNA) has been shown to attenuate hypertrophy, interstitial fibrosis and the rise of ANP levels in aortic banded mice. We detected that the depletion of MEF2C also results in lowered levels of both PGC-1alpha and mitochondrial DNA in the overloaded left ventricle, associated with enhanced AMP:ATP ratio. Additionally, MEF2C depletion was accompanied by defective activation of S6K in response to pressure overload. Treatment with the amino acid leucine stimulated S6K and suppressed the attenuation of left ventricular hypertrophy and fibrosis in the aforementioned aortic banded mice. These findings represent new evidences that MEF2C depletion attenuates the hypertrophic responses to mechanical stress and highlight the potential of MEF2C to be a target for new therapies to cardiac hypertrophy and failure.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20041152</pmid><doi>10.1371/journal.pone.0008472</doi><tpages>e8472</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2009-12, Vol.4 (12), p.e8472-e8472
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1292309875
source MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS)
subjects Activation
Amino acids
AMP
Animals
Aorta
Atherosclerosis
Attenuation
Biochemistry/Cell Signaling and Trafficking Structures
Biochemistry/Transcription and Translation
Biosynthesis
Cardiomyocytes
Cardiomyopathy
Cardiovascular Disorders/Heart Failure
Cell Biology/Cell Growth and Division
Cell growth
Cells, Cultured
Deoxyribonucleic acid
Depletion
DNA
DNA binding proteins
DNA, Mitochondrial - genetics
Fibrosis
Gene Silencing
Heart
Heart diseases
Heart failure
Heart hypertrophy
Hemodynamics
Hypertrophy
Hypertrophy, Left Ventricular - enzymology
Hypertrophy, Left Ventricular - physiopathology
Internal medicine
Intracellular Signaling Peptides and Proteins - metabolism
Kinases
Leucine
Medicine
MEF2 Transcription Factors
Mice
Mitochondrial DNA
Myocardium - enzymology
Myocardium - pathology
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
Myogenic Regulatory Factors - genetics
Myogenic Regulatory Factors - metabolism
Pathogenesis
Pressure
Protein expression
Protein synthesis
Protein-Serine-Threonine Kinases - metabolism
Proteins
Rats
Ribonucleic acid
Ribosomal Protein S6 Kinases, 90-kDa - metabolism
RNA
RNA, Small Interfering - metabolism
Rodents
Signal Transduction
siRNA
Stem cells
TOR protein
TOR Serine-Threonine Kinases
Transcription factors
Ventricle
Ventricular Pressure - physiology
title MEF2C silencing attenuates load-induced left ventricular hypertrophy by modulating mTOR/S6K pathway in mice
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T00%3A52%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=MEF2C%20silencing%20attenuates%20load-induced%20left%20ventricular%20hypertrophy%20by%20modulating%20mTOR/S6K%20pathway%20in%20mice&rft.jtitle=PloS%20one&rft.au=Pereira,%20Ana%20Helena%20M&rft.date=2009-12-29&rft.volume=4&rft.issue=12&rft.spage=e8472&rft.epage=e8472&rft.pages=e8472-e8472&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0008472&rft_dat=%3Cgale_plos_%3EA472751659%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1292309875&rft_id=info:pmid/20041152&rft_galeid=A472751659&rft_doaj_id=oai_doaj_org_article_3c8f0d18666843bb96e89875de924440&rfr_iscdi=true