Androgens contribute to sex differences in myocardial remodeling under pressure overload by a mechanism involving TGF-β

In clinical studies, myocardial remodeling in aortic valve stenosis appears to be more favorable in women than in men, even after menopause. In the present study, we assessed whether circulating androgens contribute to a less favorable myocardial remodeling under pressure overload in males. We exami...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one 2012, Vol.7 (4), p.e35635
Hauptverfasser: Montalvo, Cecilia, Villar, Ana V, Merino, David, García, Raquel, Ares, Miguel, Llano, Miguel, Cobo, Manuel, Hurlé, María A, Nistal, J Francisco
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
container_issue 4
container_start_page e35635
container_title PloS one
container_volume 7
creator Montalvo, Cecilia
Villar, Ana V
Merino, David
García, Raquel
Ares, Miguel
Llano, Miguel
Cobo, Manuel
Hurlé, María A
Nistal, J Francisco
description In clinical studies, myocardial remodeling in aortic valve stenosis appears to be more favorable in women than in men, even after menopause. In the present study, we assessed whether circulating androgens contribute to a less favorable myocardial remodeling under pressure overload in males. We examined sex-related differences in one-year-old male and female mice. Whereas male mice at this age exhibited circulating androgen levels within the normal range for young adults, the circulating estrogens in females were reduced. The contribution of gonadal androgens to cardiac remodeling was analyzed in a group of same-age castrated mice. Animals were subjected to transverse aortic constriction (TAC). Echocardiography was performed 2 weeks after TAC and myocardial mRNA levels of TGF-βs, Smads 2 and 3, collagens, fibronectin, β-myosin heavy chain and α-myosin heavy chain were determined by q-PCR. Protein detection of p-SMAD2/3 was performed by Western Blot. Histological staining of fibrosis was performed with picrosirius red and Masson's trichrome. Compared with females, males developed more severe tissue fibrosis, LV dilation and hemodynamic dysfunction. TAC-males showed higher myocardial expression levels of TGF-βs and the treatment with a neutralizing antibody to TGF-β prevented myocardial fibrosis development. Orchiectomy diminished TAC-induced up-regulation of TGF-βs and TGF-β target genes, and it also reduced fibrosis and hemodynamic dysfunction. The capability of androgens to induce TGF-β expression was confirmed in NIH-3T3 fibroblasts and H9C2 cardiomyocytes exposed to dihydrotestosterone. Our results indicate that circulating androgens are responsible for the detrimental effects in the myocardium of older male mice subjected to pressure overload through a mechanism involving TGF-βs.
doi_str_mv 10.1371/journal.pone.0035635
format Article
fullrecord <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_1324590325</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_c0ae32a71e434f96838c3c000749c75f</doaj_id><sourcerecordid>2939322001</sourcerecordid><originalsourceid>FETCH-LOGICAL-c526t-9f19be25725ac767058ec2235dd8cc82f97d9d5bb134226fbc1929b0fe2516db3</originalsourceid><addsrcrecordid>eNp1ksFu1DAQhiMEoqXwBggscc5ie-IkviBVFS2VKnEpZ8uxx1uvEnuxk1X3tfogPBNZNq3aAydbnv_7Zzz6i-IjoysGDfu6iVMKul9tY8AVpSBqEK-KUyaBlzWn8PrZ_aR4l_OGUgFtXb8tTjgXomVtdVrcnweb4hpDJiaGMfluGpGMkWS8J9Y7hwmDwUx8IMM-Gp2s1z1JOESLvQ9rMgWLiWwT5jwlJHGHqY_akm5PNBnQ3Ong8zDzu9jvDsDt1WX55-F98cbpPuOH5Twrfl1-v734Ud78vLq-OL8pjeD1WErHZIdcNFxo09QNFS0azkFY2xrTcicbK63oOgYV57XrDJNcdtTNDKttB2fF56Pvto9ZLUvLigGvhKTAxay4Pips1Bu1TX7Qaa-i9urfQ0xrpdPoTY_KUI3AdcOwgsrJuoXWgKGUNpU0jXCz17el29QNaA3OK9X9C9OXleDv1DruFAC08wdmgy-LQYq_J8zjf0aujiqTYs4J3VMHRtUhHY-UOqRDLemYsU_Pp3uCHuMAfwEjH7tP</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1324590325</pqid></control><display><type>article</type><title>Androgens contribute to sex differences in myocardial remodeling under pressure overload by a mechanism involving TGF-β</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Montalvo, Cecilia ; Villar, Ana V ; Merino, David ; García, Raquel ; Ares, Miguel ; Llano, Miguel ; Cobo, Manuel ; Hurlé, María A ; Nistal, J Francisco</creator><contributor>Abbate, Antonio</contributor><creatorcontrib>Montalvo, Cecilia ; Villar, Ana V ; Merino, David ; García, Raquel ; Ares, Miguel ; Llano, Miguel ; Cobo, Manuel ; Hurlé, María A ; Nistal, J Francisco ; Abbate, Antonio</creatorcontrib><description>In clinical studies, myocardial remodeling in aortic valve stenosis appears to be more favorable in women than in men, even after menopause. In the present study, we assessed whether circulating androgens contribute to a less favorable myocardial remodeling under pressure overload in males. We examined sex-related differences in one-year-old male and female mice. Whereas male mice at this age exhibited circulating androgen levels within the normal range for young adults, the circulating estrogens in females were reduced. The contribution of gonadal androgens to cardiac remodeling was analyzed in a group of same-age castrated mice. Animals were subjected to transverse aortic constriction (TAC). Echocardiography was performed 2 weeks after TAC and myocardial mRNA levels of TGF-βs, Smads 2 and 3, collagens, fibronectin, β-myosin heavy chain and α-myosin heavy chain were determined by q-PCR. Protein detection of p-SMAD2/3 was performed by Western Blot. Histological staining of fibrosis was performed with picrosirius red and Masson's trichrome. Compared with females, males developed more severe tissue fibrosis, LV dilation and hemodynamic dysfunction. TAC-males showed higher myocardial expression levels of TGF-βs and the treatment with a neutralizing antibody to TGF-β prevented myocardial fibrosis development. Orchiectomy diminished TAC-induced up-regulation of TGF-βs and TGF-β target genes, and it also reduced fibrosis and hemodynamic dysfunction. The capability of androgens to induce TGF-β expression was confirmed in NIH-3T3 fibroblasts and H9C2 cardiomyocytes exposed to dihydrotestosterone. Our results indicate that circulating androgens are responsible for the detrimental effects in the myocardium of older male mice subjected to pressure overload through a mechanism involving TGF-βs.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0035635</identifier><identifier>PMID: 22558184</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Adults ; Androgens ; Androgens - blood ; Androgens - pharmacology ; Animals ; Antibodies - administration &amp; dosage ; Aorta ; Aorta - metabolism ; Aorta - pathology ; Aortic valve ; Atherosclerosis ; Biology ; Blood Pressure - drug effects ; Cardiac Myosins - genetics ; Cardiac Myosins - metabolism ; Cardiomyocytes ; Cell growth ; Cells, Cultured ; Chains ; Collagen ; Collagen - genetics ; Collagen - metabolism ; Constriction ; Coronary vessels ; Dihydrotestosterone ; Echocardiography ; Estrogens ; Extracellular matrix ; Female ; Females ; Fibroblasts ; Fibronectin ; Fibronectins - genetics ; Fibronectins - metabolism ; Fibrosis ; Fibrosis - metabolism ; Fibrosis - pathology ; Gender aspects ; Gene expression ; Gene Expression - drug effects ; Heart diseases ; Heart failure ; Humans ; Hypertension ; Immunoassay ; Laboratory animals ; Male ; Males ; Medicine ; Menopause ; Mens health ; Metabolism ; Mice ; mRNA ; Myocardium ; Myocardium - metabolism ; Myocardium - pathology ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - pathology ; Myosin ; Orchiectomy ; Pressure ; Rheumatic heart disease ; Rodents ; Sex ; Sex Characteristics ; Sex differences ; Smad Proteins - genetics ; Smad Proteins - metabolism ; Smad2 protein ; Stenosis ; Testosterone ; Transforming Growth Factor beta - antagonists &amp; inhibitors ; Transforming Growth Factor beta - genetics ; Transforming Growth Factor beta - metabolism ; Ventricular Remodeling - drug effects ; Young adults</subject><ispartof>PloS one, 2012, Vol.7 (4), p.e35635</ispartof><rights>2012 Montalvo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (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>Montalvo et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-9f19be25725ac767058ec2235dd8cc82f97d9d5bb134226fbc1929b0fe2516db3</citedby><cites>FETCH-LOGICAL-c526t-9f19be25725ac767058ec2235dd8cc82f97d9d5bb134226fbc1929b0fe2516db3</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/PMC3338422/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338422/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,4024,23866,27923,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22558184$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Abbate, Antonio</contributor><creatorcontrib>Montalvo, Cecilia</creatorcontrib><creatorcontrib>Villar, Ana V</creatorcontrib><creatorcontrib>Merino, David</creatorcontrib><creatorcontrib>García, Raquel</creatorcontrib><creatorcontrib>Ares, Miguel</creatorcontrib><creatorcontrib>Llano, Miguel</creatorcontrib><creatorcontrib>Cobo, Manuel</creatorcontrib><creatorcontrib>Hurlé, María A</creatorcontrib><creatorcontrib>Nistal, J Francisco</creatorcontrib><title>Androgens contribute to sex differences in myocardial remodeling under pressure overload by a mechanism involving TGF-β</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In clinical studies, myocardial remodeling in aortic valve stenosis appears to be more favorable in women than in men, even after menopause. In the present study, we assessed whether circulating androgens contribute to a less favorable myocardial remodeling under pressure overload in males. We examined sex-related differences in one-year-old male and female mice. Whereas male mice at this age exhibited circulating androgen levels within the normal range for young adults, the circulating estrogens in females were reduced. The contribution of gonadal androgens to cardiac remodeling was analyzed in a group of same-age castrated mice. Animals were subjected to transverse aortic constriction (TAC). Echocardiography was performed 2 weeks after TAC and myocardial mRNA levels of TGF-βs, Smads 2 and 3, collagens, fibronectin, β-myosin heavy chain and α-myosin heavy chain were determined by q-PCR. Protein detection of p-SMAD2/3 was performed by Western Blot. Histological staining of fibrosis was performed with picrosirius red and Masson's trichrome. Compared with females, males developed more severe tissue fibrosis, LV dilation and hemodynamic dysfunction. TAC-males showed higher myocardial expression levels of TGF-βs and the treatment with a neutralizing antibody to TGF-β prevented myocardial fibrosis development. Orchiectomy diminished TAC-induced up-regulation of TGF-βs and TGF-β target genes, and it also reduced fibrosis and hemodynamic dysfunction. The capability of androgens to induce TGF-β expression was confirmed in NIH-3T3 fibroblasts and H9C2 cardiomyocytes exposed to dihydrotestosterone. Our results indicate that circulating androgens are responsible for the detrimental effects in the myocardium of older male mice subjected to pressure overload through a mechanism involving TGF-βs.</description><subject>Adult</subject><subject>Adults</subject><subject>Androgens</subject><subject>Androgens - blood</subject><subject>Androgens - pharmacology</subject><subject>Animals</subject><subject>Antibodies - administration &amp; dosage</subject><subject>Aorta</subject><subject>Aorta - metabolism</subject><subject>Aorta - pathology</subject><subject>Aortic valve</subject><subject>Atherosclerosis</subject><subject>Biology</subject><subject>Blood Pressure - drug effects</subject><subject>Cardiac Myosins - genetics</subject><subject>Cardiac Myosins - metabolism</subject><subject>Cardiomyocytes</subject><subject>Cell growth</subject><subject>Cells, Cultured</subject><subject>Chains</subject><subject>Collagen</subject><subject>Collagen - genetics</subject><subject>Collagen - metabolism</subject><subject>Constriction</subject><subject>Coronary vessels</subject><subject>Dihydrotestosterone</subject><subject>Echocardiography</subject><subject>Estrogens</subject><subject>Extracellular matrix</subject><subject>Female</subject><subject>Females</subject><subject>Fibroblasts</subject><subject>Fibronectin</subject><subject>Fibronectins - genetics</subject><subject>Fibronectins - metabolism</subject><subject>Fibrosis</subject><subject>Fibrosis - metabolism</subject><subject>Fibrosis - pathology</subject><subject>Gender aspects</subject><subject>Gene expression</subject><subject>Gene Expression - drug effects</subject><subject>Heart diseases</subject><subject>Heart failure</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Immunoassay</subject><subject>Laboratory animals</subject><subject>Male</subject><subject>Males</subject><subject>Medicine</subject><subject>Menopause</subject><subject>Mens health</subject><subject>Metabolism</subject><subject>Mice</subject><subject>mRNA</subject><subject>Myocardium</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - pathology</subject><subject>Myosin</subject><subject>Orchiectomy</subject><subject>Pressure</subject><subject>Rheumatic heart disease</subject><subject>Rodents</subject><subject>Sex</subject><subject>Sex Characteristics</subject><subject>Sex differences</subject><subject>Smad Proteins - genetics</subject><subject>Smad Proteins - metabolism</subject><subject>Smad2 protein</subject><subject>Stenosis</subject><subject>Testosterone</subject><subject>Transforming Growth Factor beta - antagonists &amp; inhibitors</subject><subject>Transforming Growth Factor beta - genetics</subject><subject>Transforming Growth Factor beta - metabolism</subject><subject>Ventricular Remodeling - drug effects</subject><subject>Young adults</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNp1ksFu1DAQhiMEoqXwBggscc5ie-IkviBVFS2VKnEpZ8uxx1uvEnuxk1X3tfogPBNZNq3aAydbnv_7Zzz6i-IjoysGDfu6iVMKul9tY8AVpSBqEK-KUyaBlzWn8PrZ_aR4l_OGUgFtXb8tTjgXomVtdVrcnweb4hpDJiaGMfluGpGMkWS8J9Y7hwmDwUx8IMM-Gp2s1z1JOESLvQ9rMgWLiWwT5jwlJHGHqY_akm5PNBnQ3Ong8zDzu9jvDsDt1WX55-F98cbpPuOH5Twrfl1-v734Ud78vLq-OL8pjeD1WErHZIdcNFxo09QNFS0azkFY2xrTcicbK63oOgYV57XrDJNcdtTNDKttB2fF56Pvto9ZLUvLigGvhKTAxay4Pips1Bu1TX7Qaa-i9urfQ0xrpdPoTY_KUI3AdcOwgsrJuoXWgKGUNpU0jXCz17el29QNaA3OK9X9C9OXleDv1DruFAC08wdmgy-LQYq_J8zjf0aujiqTYs4J3VMHRtUhHY-UOqRDLemYsU_Pp3uCHuMAfwEjH7tP</recordid><startdate>2012</startdate><enddate>2012</enddate><creator>Montalvo, Cecilia</creator><creator>Villar, Ana V</creator><creator>Merino, David</creator><creator>García, Raquel</creator><creator>Ares, Miguel</creator><creator>Llano, Miguel</creator><creator>Cobo, Manuel</creator><creator>Hurlé, María A</creator><creator>Nistal, J Francisco</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>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>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>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>2012</creationdate><title>Androgens contribute to sex differences in myocardial remodeling under pressure overload by a mechanism involving TGF-β</title><author>Montalvo, Cecilia ; Villar, Ana V ; Merino, David ; García, Raquel ; Ares, Miguel ; Llano, Miguel ; Cobo, Manuel ; Hurlé, María A ; Nistal, J Francisco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-9f19be25725ac767058ec2235dd8cc82f97d9d5bb134226fbc1929b0fe2516db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Adults</topic><topic>Androgens</topic><topic>Androgens - blood</topic><topic>Androgens - pharmacology</topic><topic>Animals</topic><topic>Antibodies - administration &amp; dosage</topic><topic>Aorta</topic><topic>Aorta - metabolism</topic><topic>Aorta - pathology</topic><topic>Aortic valve</topic><topic>Atherosclerosis</topic><topic>Biology</topic><topic>Blood Pressure - drug effects</topic><topic>Cardiac Myosins - genetics</topic><topic>Cardiac Myosins - metabolism</topic><topic>Cardiomyocytes</topic><topic>Cell growth</topic><topic>Cells, Cultured</topic><topic>Chains</topic><topic>Collagen</topic><topic>Collagen - genetics</topic><topic>Collagen - metabolism</topic><topic>Constriction</topic><topic>Coronary vessels</topic><topic>Dihydrotestosterone</topic><topic>Echocardiography</topic><topic>Estrogens</topic><topic>Extracellular matrix</topic><topic>Female</topic><topic>Females</topic><topic>Fibroblasts</topic><topic>Fibronectin</topic><topic>Fibronectins - genetics</topic><topic>Fibronectins - metabolism</topic><topic>Fibrosis</topic><topic>Fibrosis - metabolism</topic><topic>Fibrosis - pathology</topic><topic>Gender aspects</topic><topic>Gene expression</topic><topic>Gene Expression - drug effects</topic><topic>Heart diseases</topic><topic>Heart failure</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Immunoassay</topic><topic>Laboratory animals</topic><topic>Male</topic><topic>Males</topic><topic>Medicine</topic><topic>Menopause</topic><topic>Mens health</topic><topic>Metabolism</topic><topic>Mice</topic><topic>mRNA</topic><topic>Myocardium</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - pathology</topic><topic>Myosin</topic><topic>Orchiectomy</topic><topic>Pressure</topic><topic>Rheumatic heart disease</topic><topic>Rodents</topic><topic>Sex</topic><topic>Sex Characteristics</topic><topic>Sex differences</topic><topic>Smad Proteins - genetics</topic><topic>Smad Proteins - metabolism</topic><topic>Smad2 protein</topic><topic>Stenosis</topic><topic>Testosterone</topic><topic>Transforming Growth Factor beta - antagonists &amp; inhibitors</topic><topic>Transforming Growth Factor beta - genetics</topic><topic>Transforming Growth Factor beta - metabolism</topic><topic>Ventricular Remodeling - drug effects</topic><topic>Young adults</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Montalvo, Cecilia</creatorcontrib><creatorcontrib>Villar, Ana V</creatorcontrib><creatorcontrib>Merino, David</creatorcontrib><creatorcontrib>García, Raquel</creatorcontrib><creatorcontrib>Ares, Miguel</creatorcontrib><creatorcontrib>Llano, Miguel</creatorcontrib><creatorcontrib>Cobo, Manuel</creatorcontrib><creatorcontrib>Hurlé, María A</creatorcontrib><creatorcontrib>Nistal, J Francisco</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; Allied Health Database</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 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>Access via ProQuest (Open Access)</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 China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</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>Montalvo, Cecilia</au><au>Villar, Ana V</au><au>Merino, David</au><au>García, Raquel</au><au>Ares, Miguel</au><au>Llano, Miguel</au><au>Cobo, Manuel</au><au>Hurlé, María A</au><au>Nistal, J Francisco</au><au>Abbate, Antonio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Androgens contribute to sex differences in myocardial remodeling under pressure overload by a mechanism involving TGF-β</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012</date><risdate>2012</risdate><volume>7</volume><issue>4</issue><spage>e35635</spage><pages>e35635-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>In clinical studies, myocardial remodeling in aortic valve stenosis appears to be more favorable in women than in men, even after menopause. In the present study, we assessed whether circulating androgens contribute to a less favorable myocardial remodeling under pressure overload in males. We examined sex-related differences in one-year-old male and female mice. Whereas male mice at this age exhibited circulating androgen levels within the normal range for young adults, the circulating estrogens in females were reduced. The contribution of gonadal androgens to cardiac remodeling was analyzed in a group of same-age castrated mice. Animals were subjected to transverse aortic constriction (TAC). Echocardiography was performed 2 weeks after TAC and myocardial mRNA levels of TGF-βs, Smads 2 and 3, collagens, fibronectin, β-myosin heavy chain and α-myosin heavy chain were determined by q-PCR. Protein detection of p-SMAD2/3 was performed by Western Blot. Histological staining of fibrosis was performed with picrosirius red and Masson's trichrome. Compared with females, males developed more severe tissue fibrosis, LV dilation and hemodynamic dysfunction. TAC-males showed higher myocardial expression levels of TGF-βs and the treatment with a neutralizing antibody to TGF-β prevented myocardial fibrosis development. Orchiectomy diminished TAC-induced up-regulation of TGF-βs and TGF-β target genes, and it also reduced fibrosis and hemodynamic dysfunction. The capability of androgens to induce TGF-β expression was confirmed in NIH-3T3 fibroblasts and H9C2 cardiomyocytes exposed to dihydrotestosterone. Our results indicate that circulating androgens are responsible for the detrimental effects in the myocardium of older male mice subjected to pressure overload through a mechanism involving TGF-βs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22558184</pmid><doi>10.1371/journal.pone.0035635</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2012, Vol.7 (4), p.e35635
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1324590325
source MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry
subjects Adult
Adults
Androgens
Androgens - blood
Androgens - pharmacology
Animals
Antibodies - administration & dosage
Aorta
Aorta - metabolism
Aorta - pathology
Aortic valve
Atherosclerosis
Biology
Blood Pressure - drug effects
Cardiac Myosins - genetics
Cardiac Myosins - metabolism
Cardiomyocytes
Cell growth
Cells, Cultured
Chains
Collagen
Collagen - genetics
Collagen - metabolism
Constriction
Coronary vessels
Dihydrotestosterone
Echocardiography
Estrogens
Extracellular matrix
Female
Females
Fibroblasts
Fibronectin
Fibronectins - genetics
Fibronectins - metabolism
Fibrosis
Fibrosis - metabolism
Fibrosis - pathology
Gender aspects
Gene expression
Gene Expression - drug effects
Heart diseases
Heart failure
Humans
Hypertension
Immunoassay
Laboratory animals
Male
Males
Medicine
Menopause
Mens health
Metabolism
Mice
mRNA
Myocardium
Myocardium - metabolism
Myocardium - pathology
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - pathology
Myosin
Orchiectomy
Pressure
Rheumatic heart disease
Rodents
Sex
Sex Characteristics
Sex differences
Smad Proteins - genetics
Smad Proteins - metabolism
Smad2 protein
Stenosis
Testosterone
Transforming Growth Factor beta - antagonists & inhibitors
Transforming Growth Factor beta - genetics
Transforming Growth Factor beta - metabolism
Ventricular Remodeling - drug effects
Young adults
title Androgens contribute to sex differences in myocardial remodeling under pressure overload by a mechanism involving TGF-β
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T18%3A54%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Androgens%20contribute%20to%20sex%20differences%20in%20myocardial%20remodeling%20under%20pressure%20overload%20by%20a%20mechanism%20involving%20TGF-%CE%B2&rft.jtitle=PloS%20one&rft.au=Montalvo,%20Cecilia&rft.date=2012&rft.volume=7&rft.issue=4&rft.spage=e35635&rft.pages=e35635-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0035635&rft_dat=%3Cproquest_plos_%3E2939322001%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1324590325&rft_id=info:pmid/22558184&rft_doaj_id=oai_doaj_org_article_c0ae32a71e434f96838c3c000749c75f&rfr_iscdi=true