Regulation of cAMP homeostasis by the efflux protein MRP4 in cardiac myocytes
Recent studies indicate that members of the multidrug‐resistance protein (MRP) family belonging to ATP binding cassette type C (ABCC) membrane proteins extrude cyclic nucleotides from various cell types. This study aimed to determine whether MRP proteins regulate cardiac cAMP homeostasis. Here, we d...
Gespeichert in:
| Veröffentlicht in: | The FASEB journal 2012-03, Vol.26 (3), p.1009-1017 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1017 |
|---|---|
| container_issue | 3 |
| container_start_page | 1009 |
| container_title | The FASEB journal |
| container_volume | 26 |
| creator | Sassi, Yassine Abi‐Gerges, Aniella Fauconnier, Jeremy Mougenot, Nathalie Reiken, Steven Haghighi, Kobra Kranias, Evangelia G. Marks, Andrew R. Lacampagne, Alain Engelhardt, Stefan Hatem, Stephane N. Lompre, Anne‐Marie Hulot, Jean‐Sébastien |
| description | Recent studies indicate that members of the multidrug‐resistance protein (MRP) family belonging to ATP binding cassette type C (ABCC) membrane proteins extrude cyclic nucleotides from various cell types. This study aimed to determine whether MRP proteins regulate cardiac cAMP homeostasis. Here, we demonstrate that MRP4 is the predominant isoform present at the plasma membrane of cardiacmyocytes and that it mediates the efflux of cAMP in these cells. MRP4‐deficient mice displayed enhanced cardiac myocyte cAMP formation, contractility, and cardiac hypertrophy at 9 mo of age, an effect that was compensated transiently by increased phosphodiesterase expression at young age. These findings suggest that cAMP extrusion via MRP4 acts together with phosphodiesterases to control cAMP levels in cardiac myocytes.—Sassi, Y., Abi‐Gerges, A., Fauconnier, J., Mougenot, N., Reiken, S., Haghighi, K., Kranias, E. G., Marks, A. R., Lacampagne, A., Engelhardt, S., Hatem, S. N., Lompre, A.‐M., Hulot, J. S. Regulation of cAMP homeostasis by the efflux protein MRP4 in cardiac myocytes. FASEB J. 26, 1009‐1017 (2012). www.fasebj.org |
| doi_str_mv | 10.1096/fj.11-194027 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3289499</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>926154108</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4977-92f98ca1fc4a7d7c74bec4a27d5b8f69e3f12b5773b2d9a05bffb2135fc888aa3</originalsourceid><addsrcrecordid>eNp9kU1v1DAQhq0K1C6FW8_INy5NmbETf1yQ2ooCUldUBc6W49hdr5J4GydA_j1B21b0wmlGmkfPjOYl5AThDEGL92F7hligLoHJA7LCikMhlIAXZAVKs0IIro7Iq5y3AICA4pAcMQYaOIoVWd_6u6m1Y0w9TYG68_UN3aTOpzzaHDOtZzpuPPUhtNNvuhvS6GNP17c3JV2qs0MTraPdnNw8-vyavAy2zf7NQz0mP64-fr_8XFx__fTl8vy6cKWWstAsaOUsBlda2Ugny9ovLZNNVasgtOcBWV1JyWvWaAtVHULNkFfBKaWs5cfkw967m-rON87342BbsxtiZ4fZJBvN80kfN-Yu_TScKV1qvQjePQiGdD_5PJouZufb1vY-TdloJrAqEdRCnu5JN6ScBx-etiCYvwGYsDWIZh_Agr_997In-PHjCyD3wK_Y-vm_MnP17YIBEwAcQPI_9Z2Smg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>926154108</pqid></control><display><type>article</type><title>Regulation of cAMP homeostasis by the efflux protein MRP4 in cardiac myocytes</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Alma/SFX Local Collection</source><creator>Sassi, Yassine ; Abi‐Gerges, Aniella ; Fauconnier, Jeremy ; Mougenot, Nathalie ; Reiken, Steven ; Haghighi, Kobra ; Kranias, Evangelia G. ; Marks, Andrew R. ; Lacampagne, Alain ; Engelhardt, Stefan ; Hatem, Stephane N. ; Lompre, Anne‐Marie ; Hulot, Jean‐Sébastien</creator><creatorcontrib>Sassi, Yassine ; Abi‐Gerges, Aniella ; Fauconnier, Jeremy ; Mougenot, Nathalie ; Reiken, Steven ; Haghighi, Kobra ; Kranias, Evangelia G. ; Marks, Andrew R. ; Lacampagne, Alain ; Engelhardt, Stefan ; Hatem, Stephane N. ; Lompre, Anne‐Marie ; Hulot, Jean‐Sébastien</creatorcontrib><description>Recent studies indicate that members of the multidrug‐resistance protein (MRP) family belonging to ATP binding cassette type C (ABCC) membrane proteins extrude cyclic nucleotides from various cell types. This study aimed to determine whether MRP proteins regulate cardiac cAMP homeostasis. Here, we demonstrate that MRP4 is the predominant isoform present at the plasma membrane of cardiacmyocytes and that it mediates the efflux of cAMP in these cells. MRP4‐deficient mice displayed enhanced cardiac myocyte cAMP formation, contractility, and cardiac hypertrophy at 9 mo of age, an effect that was compensated transiently by increased phosphodiesterase expression at young age. These findings suggest that cAMP extrusion via MRP4 acts together with phosphodiesterases to control cAMP levels in cardiac myocytes.—Sassi, Y., Abi‐Gerges, A., Fauconnier, J., Mougenot, N., Reiken, S., Haghighi, K., Kranias, E. G., Marks, A. R., Lacampagne, A., Engelhardt, S., Hatem, S. N., Lompre, A.‐M., Hulot, J. S. Regulation of cAMP homeostasis by the efflux protein MRP4 in cardiac myocytes. FASEB J. 26, 1009‐1017 (2012). www.fasebj.org</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.11-194027</identifier><identifier>PMID: 22090316</identifier><language>eng</language><publisher>Bethesda, MD, USA: Federation of American Societies for Experimental Biology</publisher><subject>1-Methyl-3-isobutylxanthine - pharmacology ; Animals ; Blotting, Western ; Cardiomegaly - diagnostic imaging ; Cardiomegaly - genetics ; Cardiomegaly - metabolism ; Cell Membrane - metabolism ; Cells, Cultured ; Cyclic AMP - metabolism ; cyclic nucleotides ; Echocardiography ; Female ; Gene Expression Regulation, Enzymologic ; Homeostasis ; Isoenzymes - genetics ; Isoenzymes - metabolism ; Male ; Mice ; Mice, Knockout ; Microscopy, Confocal ; MRP proteins ; Multidrug Resistance-Associated Proteins - genetics ; Multidrug Resistance-Associated Proteins - metabolism ; Myocardial Contraction - genetics ; Myocardial Contraction - physiology ; Myocytes, Cardiac - cytology ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - metabolism ; Phosphodiesterase Inhibitors - pharmacology ; phosphodiesterases ; Phosphoric Diester Hydrolases - genetics ; Phosphoric Diester Hydrolases - metabolism ; Rats ; Research Communications ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors</subject><ispartof>The FASEB journal, 2012-03, Vol.26 (3), p.1009-1017</ispartof><rights>FASEB</rights><rights>FASEB 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4977-92f98ca1fc4a7d7c74bec4a27d5b8f69e3f12b5773b2d9a05bffb2135fc888aa3</citedby><cites>FETCH-LOGICAL-c4977-92f98ca1fc4a7d7c74bec4a27d5b8f69e3f12b5773b2d9a05bffb2135fc888aa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.11-194027$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.11-194027$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22090316$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sassi, Yassine</creatorcontrib><creatorcontrib>Abi‐Gerges, Aniella</creatorcontrib><creatorcontrib>Fauconnier, Jeremy</creatorcontrib><creatorcontrib>Mougenot, Nathalie</creatorcontrib><creatorcontrib>Reiken, Steven</creatorcontrib><creatorcontrib>Haghighi, Kobra</creatorcontrib><creatorcontrib>Kranias, Evangelia G.</creatorcontrib><creatorcontrib>Marks, Andrew R.</creatorcontrib><creatorcontrib>Lacampagne, Alain</creatorcontrib><creatorcontrib>Engelhardt, Stefan</creatorcontrib><creatorcontrib>Hatem, Stephane N.</creatorcontrib><creatorcontrib>Lompre, Anne‐Marie</creatorcontrib><creatorcontrib>Hulot, Jean‐Sébastien</creatorcontrib><title>Regulation of cAMP homeostasis by the efflux protein MRP4 in cardiac myocytes</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>Recent studies indicate that members of the multidrug‐resistance protein (MRP) family belonging to ATP binding cassette type C (ABCC) membrane proteins extrude cyclic nucleotides from various cell types. This study aimed to determine whether MRP proteins regulate cardiac cAMP homeostasis. Here, we demonstrate that MRP4 is the predominant isoform present at the plasma membrane of cardiacmyocytes and that it mediates the efflux of cAMP in these cells. MRP4‐deficient mice displayed enhanced cardiac myocyte cAMP formation, contractility, and cardiac hypertrophy at 9 mo of age, an effect that was compensated transiently by increased phosphodiesterase expression at young age. These findings suggest that cAMP extrusion via MRP4 acts together with phosphodiesterases to control cAMP levels in cardiac myocytes.—Sassi, Y., Abi‐Gerges, A., Fauconnier, J., Mougenot, N., Reiken, S., Haghighi, K., Kranias, E. G., Marks, A. R., Lacampagne, A., Engelhardt, S., Hatem, S. N., Lompre, A.‐M., Hulot, J. S. Regulation of cAMP homeostasis by the efflux protein MRP4 in cardiac myocytes. FASEB J. 26, 1009‐1017 (2012). www.fasebj.org</description><subject>1-Methyl-3-isobutylxanthine - pharmacology</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cardiomegaly - diagnostic imaging</subject><subject>Cardiomegaly - genetics</subject><subject>Cardiomegaly - metabolism</subject><subject>Cell Membrane - metabolism</subject><subject>Cells, Cultured</subject><subject>Cyclic AMP - metabolism</subject><subject>cyclic nucleotides</subject><subject>Echocardiography</subject><subject>Female</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Homeostasis</subject><subject>Isoenzymes - genetics</subject><subject>Isoenzymes - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Microscopy, Confocal</subject><subject>MRP proteins</subject><subject>Multidrug Resistance-Associated Proteins - genetics</subject><subject>Multidrug Resistance-Associated Proteins - metabolism</subject><subject>Myocardial Contraction - genetics</subject><subject>Myocardial Contraction - physiology</subject><subject>Myocytes, Cardiac - cytology</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Phosphodiesterase Inhibitors - pharmacology</subject><subject>phosphodiesterases</subject><subject>Phosphoric Diester Hydrolases - genetics</subject><subject>Phosphoric Diester Hydrolases - metabolism</subject><subject>Rats</subject><subject>Research Communications</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Time Factors</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhq0K1C6FW8_INy5NmbETf1yQ2ooCUldUBc6W49hdr5J4GydA_j1B21b0wmlGmkfPjOYl5AThDEGL92F7hligLoHJA7LCikMhlIAXZAVKs0IIro7Iq5y3AICA4pAcMQYaOIoVWd_6u6m1Y0w9TYG68_UN3aTOpzzaHDOtZzpuPPUhtNNvuhvS6GNP17c3JV2qs0MTraPdnNw8-vyavAy2zf7NQz0mP64-fr_8XFx__fTl8vy6cKWWstAsaOUsBlda2Ugny9ovLZNNVasgtOcBWV1JyWvWaAtVHULNkFfBKaWs5cfkw967m-rON87342BbsxtiZ4fZJBvN80kfN-Yu_TScKV1qvQjePQiGdD_5PJouZufb1vY-TdloJrAqEdRCnu5JN6ScBx-etiCYvwGYsDWIZh_Agr_997In-PHjCyD3wK_Y-vm_MnP17YIBEwAcQPI_9Z2Smg</recordid><startdate>201203</startdate><enddate>201203</enddate><creator>Sassi, Yassine</creator><creator>Abi‐Gerges, Aniella</creator><creator>Fauconnier, Jeremy</creator><creator>Mougenot, Nathalie</creator><creator>Reiken, Steven</creator><creator>Haghighi, Kobra</creator><creator>Kranias, Evangelia G.</creator><creator>Marks, Andrew R.</creator><creator>Lacampagne, Alain</creator><creator>Engelhardt, Stefan</creator><creator>Hatem, Stephane N.</creator><creator>Lompre, Anne‐Marie</creator><creator>Hulot, Jean‐Sébastien</creator><general>Federation of American Societies for Experimental Biology</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><scope>5PM</scope></search><sort><creationdate>201203</creationdate><title>Regulation of cAMP homeostasis by the efflux protein MRP4 in cardiac myocytes</title><author>Sassi, Yassine ; Abi‐Gerges, Aniella ; Fauconnier, Jeremy ; Mougenot, Nathalie ; Reiken, Steven ; Haghighi, Kobra ; Kranias, Evangelia G. ; Marks, Andrew R. ; Lacampagne, Alain ; Engelhardt, Stefan ; Hatem, Stephane N. ; Lompre, Anne‐Marie ; Hulot, Jean‐Sébastien</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4977-92f98ca1fc4a7d7c74bec4a27d5b8f69e3f12b5773b2d9a05bffb2135fc888aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>1-Methyl-3-isobutylxanthine - pharmacology</topic><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cardiomegaly - diagnostic imaging</topic><topic>Cardiomegaly - genetics</topic><topic>Cardiomegaly - metabolism</topic><topic>Cell Membrane - metabolism</topic><topic>Cells, Cultured</topic><topic>Cyclic AMP - metabolism</topic><topic>cyclic nucleotides</topic><topic>Echocardiography</topic><topic>Female</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Homeostasis</topic><topic>Isoenzymes - genetics</topic><topic>Isoenzymes - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Microscopy, Confocal</topic><topic>MRP proteins</topic><topic>Multidrug Resistance-Associated Proteins - genetics</topic><topic>Multidrug Resistance-Associated Proteins - metabolism</topic><topic>Myocardial Contraction - genetics</topic><topic>Myocardial Contraction - physiology</topic><topic>Myocytes, Cardiac - cytology</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Phosphodiesterase Inhibitors - pharmacology</topic><topic>phosphodiesterases</topic><topic>Phosphoric Diester Hydrolases - genetics</topic><topic>Phosphoric Diester Hydrolases - metabolism</topic><topic>Rats</topic><topic>Research Communications</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sassi, Yassine</creatorcontrib><creatorcontrib>Abi‐Gerges, Aniella</creatorcontrib><creatorcontrib>Fauconnier, Jeremy</creatorcontrib><creatorcontrib>Mougenot, Nathalie</creatorcontrib><creatorcontrib>Reiken, Steven</creatorcontrib><creatorcontrib>Haghighi, Kobra</creatorcontrib><creatorcontrib>Kranias, Evangelia G.</creatorcontrib><creatorcontrib>Marks, Andrew R.</creatorcontrib><creatorcontrib>Lacampagne, Alain</creatorcontrib><creatorcontrib>Engelhardt, Stefan</creatorcontrib><creatorcontrib>Hatem, Stephane N.</creatorcontrib><creatorcontrib>Lompre, Anne‐Marie</creatorcontrib><creatorcontrib>Hulot, Jean‐Sébastien</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sassi, Yassine</au><au>Abi‐Gerges, Aniella</au><au>Fauconnier, Jeremy</au><au>Mougenot, Nathalie</au><au>Reiken, Steven</au><au>Haghighi, Kobra</au><au>Kranias, Evangelia G.</au><au>Marks, Andrew R.</au><au>Lacampagne, Alain</au><au>Engelhardt, Stefan</au><au>Hatem, Stephane N.</au><au>Lompre, Anne‐Marie</au><au>Hulot, Jean‐Sébastien</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of cAMP homeostasis by the efflux protein MRP4 in cardiac myocytes</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2012-03</date><risdate>2012</risdate><volume>26</volume><issue>3</issue><spage>1009</spage><epage>1017</epage><pages>1009-1017</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>Recent studies indicate that members of the multidrug‐resistance protein (MRP) family belonging to ATP binding cassette type C (ABCC) membrane proteins extrude cyclic nucleotides from various cell types. This study aimed to determine whether MRP proteins regulate cardiac cAMP homeostasis. Here, we demonstrate that MRP4 is the predominant isoform present at the plasma membrane of cardiacmyocytes and that it mediates the efflux of cAMP in these cells. MRP4‐deficient mice displayed enhanced cardiac myocyte cAMP formation, contractility, and cardiac hypertrophy at 9 mo of age, an effect that was compensated transiently by increased phosphodiesterase expression at young age. These findings suggest that cAMP extrusion via MRP4 acts together with phosphodiesterases to control cAMP levels in cardiac myocytes.—Sassi, Y., Abi‐Gerges, A., Fauconnier, J., Mougenot, N., Reiken, S., Haghighi, K., Kranias, E. G., Marks, A. R., Lacampagne, A., Engelhardt, S., Hatem, S. N., Lompre, A.‐M., Hulot, J. S. Regulation of cAMP homeostasis by the efflux protein MRP4 in cardiac myocytes. FASEB J. 26, 1009‐1017 (2012). www.fasebj.org</abstract><cop>Bethesda, MD, USA</cop><pub>Federation of American Societies for Experimental Biology</pub><pmid>22090316</pmid><doi>10.1096/fj.11-194027</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0892-6638 |
| ispartof | The FASEB journal, 2012-03, Vol.26 (3), p.1009-1017 |
| issn | 0892-6638 1530-6860 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3289499 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection |
| subjects | 1-Methyl-3-isobutylxanthine - pharmacology Animals Blotting, Western Cardiomegaly - diagnostic imaging Cardiomegaly - genetics Cardiomegaly - metabolism Cell Membrane - metabolism Cells, Cultured Cyclic AMP - metabolism cyclic nucleotides Echocardiography Female Gene Expression Regulation, Enzymologic Homeostasis Isoenzymes - genetics Isoenzymes - metabolism Male Mice Mice, Knockout Microscopy, Confocal MRP proteins Multidrug Resistance-Associated Proteins - genetics Multidrug Resistance-Associated Proteins - metabolism Myocardial Contraction - genetics Myocardial Contraction - physiology Myocytes, Cardiac - cytology Myocytes, Cardiac - drug effects Myocytes, Cardiac - metabolism Phosphodiesterase Inhibitors - pharmacology phosphodiesterases Phosphoric Diester Hydrolases - genetics Phosphoric Diester Hydrolases - metabolism Rats Research Communications Reverse Transcriptase Polymerase Chain Reaction Time Factors |
| title | Regulation of cAMP homeostasis by the efflux protein MRP4 in cardiac myocytes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T14%3A39%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Regulation%20of%20cAMP%20homeostasis%20by%20the%20efflux%20protein%20MRP4%20in%20cardiac%20myocytes&rft.jtitle=The%20FASEB%20journal&rft.au=Sassi,%20Yassine&rft.date=2012-03&rft.volume=26&rft.issue=3&rft.spage=1009&rft.epage=1017&rft.pages=1009-1017&rft.issn=0892-6638&rft.eissn=1530-6860&rft_id=info:doi/10.1096/fj.11-194027&rft_dat=%3Cproquest_pubme%3E926154108%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=926154108&rft_id=info:pmid/22090316&rfr_iscdi=true |