Cardiac function and architecture are maintained in a model of cardiorestricted overexpression of the prorenin-renin receptor
The (pro)renin-renin receptor, (P)RR has been claimed to be a novel element of the renin-angiotensin system (RAS). The function of (P)RR has been widely studied in renal and vascular pathology but the cardio-specific function of (P)RR has not been studied in detail. We therefore generated a transgen...
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| creator | Mahmud, Hasan Candido, Wellington Mardoqueu van Genne, Linda Vreeswijk-Baudoin, Inge Yu, Hongjuan van de Sluis, Bart van Deursen, Jan van Gilst, Wiek H Silljé, Herman H W de Boer, Rudolf A |
| description | The (pro)renin-renin receptor, (P)RR has been claimed to be a novel element of the renin-angiotensin system (RAS). The function of (P)RR has been widely studied in renal and vascular pathology but the cardio-specific function of (P)RR has not been studied in detail. We therefore generated a transgenic mouse (Tg) with cardio-restricted (P)RR overexpression driven by the alpha-MHC promotor. The mRNA expression of (P)RR was ∼ 170-fold higher (P |
| doi_str_mv | 10.1371/journal.pone.0089929 |
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The function of (P)RR has been widely studied in renal and vascular pathology but the cardio-specific function of (P)RR has not been studied in detail. We therefore generated a transgenic mouse (Tg) with cardio-restricted (P)RR overexpression driven by the alpha-MHC promotor. The mRNA expression of (P)RR was ∼ 170-fold higher (P<0.001) and protein expression ∼ 5-fold higher (P<0.001) in hearts of Tg mice as compared to non-transgenic (wild type, Wt) littermates. This level of overexpression was not associated with spontaneous cardiac morphological or functional abnormalities in Tg mice. To assess whether (P)RR could play a role in cardiac hypertrophy, we infused ISO for 28 days, but this caused an equal degree of cardiac hypertrophy and fibrosis in Wt and Tg mice. In addition, ischemia-reperfusion injury was performed in Langendorff perfused isolated mouse hearts. We did not observe differences in parameters of cardiac function or damage between Wt and Tg mouse hearts under these conditions. Finally, we explored whether the hypoxia sensing response would be modulated by (P)RR using HeLa cells with and without (P)RR overexpression. We did not establish any effect of (P)RR on expression of genes associated with the hypoxic response. These results demonstrate that cardio-specific overexpression of (P)RR does not provoke phenotypical differences in the heart, and does not affect the hearts' response to stress and injury. It is concluded that increased myocardial (P)RR expression is unlikely to have a major role in pathological cardiac remodeling.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0089929</identifier><identifier>PMID: 24587131</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abnormalities ; Acidification ; Angiotensin ; Angiotensins ; Animals ; Biology ; Blood Pressure ; Blotting, Western ; Cardiology ; Cardiomegaly - genetics ; Cardiomegaly - metabolism ; Cloning ; Creatine Kinase - metabolism ; Diabetes ; Echocardiography ; Experiments ; Fibrosis ; Gene expression ; Gene Expression Regulation - genetics ; Genetic engineering ; Heart ; Heart - physiology ; Heart diseases ; Heart failure ; HeLa Cells ; Humans ; Hypertension ; Hypertrophy ; Hypoxia ; Hypoxia - metabolism ; Ischemia ; Isoproterenol ; Kidneys ; Kinases ; L-Lactate Dehydrogenase - metabolism ; Laboratory animals ; Major histocompatibility complex ; Male ; Medicine ; Mice ; Mice, Transgenic ; Myocardium - metabolism ; Protein folding ; Real-Time Polymerase Chain Reaction ; Receptors, Cell Surface - metabolism ; Renin ; Reperfusion ; Reperfusion Injury - metabolism ; RNA ; Rodents ; Smooth muscle ; Transgenic animals ; Transgenic mice</subject><ispartof>PloS one, 2014-02, Vol.9 (2), p.e89929-e89929</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Mahmud et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://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>2014 Mahmud et al 2014 Mahmud et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-71a7e81f9f561f8af2706c171e64564974332ba1c59dcff50ac7bc5a94d183473</citedby><cites>FETCH-LOGICAL-c692t-71a7e81f9f561f8af2706c171e64564974332ba1c59dcff50ac7bc5a94d183473</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/PMC3934958/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934958/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24587131$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bader, Michael</contributor><creatorcontrib>Mahmud, Hasan</creatorcontrib><creatorcontrib>Candido, Wellington Mardoqueu</creatorcontrib><creatorcontrib>van Genne, Linda</creatorcontrib><creatorcontrib>Vreeswijk-Baudoin, Inge</creatorcontrib><creatorcontrib>Yu, Hongjuan</creatorcontrib><creatorcontrib>van de Sluis, Bart</creatorcontrib><creatorcontrib>van Deursen, Jan</creatorcontrib><creatorcontrib>van Gilst, Wiek H</creatorcontrib><creatorcontrib>Silljé, Herman H W</creatorcontrib><creatorcontrib>de Boer, Rudolf A</creatorcontrib><title>Cardiac function and architecture are maintained in a model of cardiorestricted overexpression of the prorenin-renin receptor</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The (pro)renin-renin receptor, (P)RR has been claimed to be a novel element of the renin-angiotensin system (RAS). The function of (P)RR has been widely studied in renal and vascular pathology but the cardio-specific function of (P)RR has not been studied in detail. We therefore generated a transgenic mouse (Tg) with cardio-restricted (P)RR overexpression driven by the alpha-MHC promotor. The mRNA expression of (P)RR was ∼ 170-fold higher (P<0.001) and protein expression ∼ 5-fold higher (P<0.001) in hearts of Tg mice as compared to non-transgenic (wild type, Wt) littermates. This level of overexpression was not associated with spontaneous cardiac morphological or functional abnormalities in Tg mice. To assess whether (P)RR could play a role in cardiac hypertrophy, we infused ISO for 28 days, but this caused an equal degree of cardiac hypertrophy and fibrosis in Wt and Tg mice. In addition, ischemia-reperfusion injury was performed in Langendorff perfused isolated mouse hearts. We did not observe differences in parameters of cardiac function or damage between Wt and Tg mouse hearts under these conditions. Finally, we explored whether the hypoxia sensing response would be modulated by (P)RR using HeLa cells with and without (P)RR overexpression. We did not establish any effect of (P)RR on expression of genes associated with the hypoxic response. These results demonstrate that cardio-specific overexpression of (P)RR does not provoke phenotypical differences in the heart, and does not affect the hearts' response to stress and injury. It is concluded that increased myocardial (P)RR expression is unlikely to have a major role in pathological cardiac remodeling.</description><subject>Abnormalities</subject><subject>Acidification</subject><subject>Angiotensin</subject><subject>Angiotensins</subject><subject>Animals</subject><subject>Biology</subject><subject>Blood Pressure</subject><subject>Blotting, Western</subject><subject>Cardiology</subject><subject>Cardiomegaly - genetics</subject><subject>Cardiomegaly - metabolism</subject><subject>Cloning</subject><subject>Creatine Kinase - metabolism</subject><subject>Diabetes</subject><subject>Echocardiography</subject><subject>Experiments</subject><subject>Fibrosis</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - genetics</subject><subject>Genetic engineering</subject><subject>Heart</subject><subject>Heart - physiology</subject><subject>Heart diseases</subject><subject>Heart failure</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypertrophy</subject><subject>Hypoxia</subject><subject>Hypoxia - metabolism</subject><subject>Ischemia</subject><subject>Isoproterenol</subject><subject>Kidneys</subject><subject>Kinases</subject><subject>L-Lactate Dehydrogenase - metabolism</subject><subject>Laboratory animals</subject><subject>Major histocompatibility complex</subject><subject>Male</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Myocardium - metabolism</subject><subject>Protein folding</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Renin</subject><subject>Reperfusion</subject><subject>Reperfusion Injury - metabolism</subject><subject>RNA</subject><subject>Rodents</subject><subject>Smooth muscle</subject><subject>Transgenic animals</subject><subject>Transgenic mice</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</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>eNqNk9tq3DAQhk1padK0b1BaQ6G0F7uVLMmybgph6WEhEOjpVmjl0a4W23IkOaQXfffKWSesSy6K8Wn0_b9GI02WvcRoiQnHH_Zu8J1qlr3rYIlQJUQhHmWnWJBiURaIPD76PsmehbBHiJGqLJ9mJwVlFccEn2Z_VsrXVuncDJ2O1nW56upceb2zEXQcPKQfyFtlu5huqHObkLx1NTS5M7ke5c5DiN7qmIbdNXi46VMkjG4JiTvIe5-YznaL22fuQUMfnX-ePTGqCfBiep9lPz9_-rH6uri4_LJenV8sdCmKuOBYcaiwEYaV2FTKFByVGnMMJWUlFZwSUmwU1kzU2hiGlOYbzZSgNa4I5eQse33w7RsX5FS5ILHgnDGBS5GI9YGondrL3ttW-d_SKStvA85vpfLR6gakpkwIYEQxhinDYlMhVgmGNwVnRlOcvD5Osw2bFmoNXfSqmZnORzq7k1t3LYkgVLAqGbybDLy7GlJtZWuDhqZRHbgh5c0QxSVidMz7zT_ow6ubqK1KC7CdcWlePZrKc8orLgqOx7yXD1DpqqG1Oh0zY1N8Jng_EyQmwk3cqiEEuf7-7f_Zy19z9u0RuwPVxF1wzTCezzAH6QHU3oXgwdwXGSM5dsldNeTYJXLqkiR7dbxB96K7tiB_AR1YDcw</recordid><startdate>20140225</startdate><enddate>20140225</enddate><creator>Mahmud, Hasan</creator><creator>Candido, Wellington Mardoqueu</creator><creator>van Genne, Linda</creator><creator>Vreeswijk-Baudoin, Inge</creator><creator>Yu, Hongjuan</creator><creator>van de Sluis, Bart</creator><creator>van Deursen, Jan</creator><creator>van Gilst, Wiek H</creator><creator>Silljé, Herman H W</creator><creator>de Boer, Rudolf A</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>20140225</creationdate><title>Cardiac function and architecture are maintained in a model of cardiorestricted overexpression of the prorenin-renin receptor</title><author>Mahmud, Hasan ; Candido, Wellington Mardoqueu ; van Genne, Linda ; Vreeswijk-Baudoin, Inge ; Yu, Hongjuan ; van de Sluis, Bart ; van Deursen, Jan ; van Gilst, Wiek H ; Silljé, Herman H W ; de Boer, Rudolf A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-71a7e81f9f561f8af2706c171e64564974332ba1c59dcff50ac7bc5a94d183473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Abnormalities</topic><topic>Acidification</topic><topic>Angiotensin</topic><topic>Angiotensins</topic><topic>Animals</topic><topic>Biology</topic><topic>Blood Pressure</topic><topic>Blotting, Western</topic><topic>Cardiology</topic><topic>Cardiomegaly - genetics</topic><topic>Cardiomegaly - metabolism</topic><topic>Cloning</topic><topic>Creatine Kinase - metabolism</topic><topic>Diabetes</topic><topic>Echocardiography</topic><topic>Experiments</topic><topic>Fibrosis</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - genetics</topic><topic>Genetic engineering</topic><topic>Heart</topic><topic>Heart - physiology</topic><topic>Heart diseases</topic><topic>Heart failure</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypertrophy</topic><topic>Hypoxia</topic><topic>Hypoxia - metabolism</topic><topic>Ischemia</topic><topic>Isoproterenol</topic><topic>Kidneys</topic><topic>Kinases</topic><topic>L-Lactate Dehydrogenase - metabolism</topic><topic>Laboratory animals</topic><topic>Major histocompatibility complex</topic><topic>Male</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Myocardium - metabolism</topic><topic>Protein folding</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptors, Cell Surface - 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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>Mahmud, Hasan</au><au>Candido, Wellington Mardoqueu</au><au>van Genne, Linda</au><au>Vreeswijk-Baudoin, Inge</au><au>Yu, Hongjuan</au><au>van de Sluis, Bart</au><au>van Deursen, Jan</au><au>van Gilst, Wiek H</au><au>Silljé, Herman H W</au><au>de Boer, Rudolf A</au><au>Bader, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cardiac function and architecture are maintained in a model of cardiorestricted overexpression of the prorenin-renin receptor</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-02-25</date><risdate>2014</risdate><volume>9</volume><issue>2</issue><spage>e89929</spage><epage>e89929</epage><pages>e89929-e89929</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The (pro)renin-renin receptor, (P)RR has been claimed to be a novel element of the renin-angiotensin system (RAS). The function of (P)RR has been widely studied in renal and vascular pathology but the cardio-specific function of (P)RR has not been studied in detail. We therefore generated a transgenic mouse (Tg) with cardio-restricted (P)RR overexpression driven by the alpha-MHC promotor. The mRNA expression of (P)RR was ∼ 170-fold higher (P<0.001) and protein expression ∼ 5-fold higher (P<0.001) in hearts of Tg mice as compared to non-transgenic (wild type, Wt) littermates. This level of overexpression was not associated with spontaneous cardiac morphological or functional abnormalities in Tg mice. To assess whether (P)RR could play a role in cardiac hypertrophy, we infused ISO for 28 days, but this caused an equal degree of cardiac hypertrophy and fibrosis in Wt and Tg mice. In addition, ischemia-reperfusion injury was performed in Langendorff perfused isolated mouse hearts. We did not observe differences in parameters of cardiac function or damage between Wt and Tg mouse hearts under these conditions. Finally, we explored whether the hypoxia sensing response would be modulated by (P)RR using HeLa cells with and without (P)RR overexpression. We did not establish any effect of (P)RR on expression of genes associated with the hypoxic response. These results demonstrate that cardio-specific overexpression of (P)RR does not provoke phenotypical differences in the heart, and does not affect the hearts' response to stress and injury. It is concluded that increased myocardial (P)RR expression is unlikely to have a major role in pathological cardiac remodeling.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24587131</pmid><doi>10.1371/journal.pone.0089929</doi><tpages>e89929</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-02, Vol.9 (2), p.e89929-e89929 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1977559169 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Abnormalities Acidification Angiotensin Angiotensins Animals Biology Blood Pressure Blotting, Western Cardiology Cardiomegaly - genetics Cardiomegaly - metabolism Cloning Creatine Kinase - metabolism Diabetes Echocardiography Experiments Fibrosis Gene expression Gene Expression Regulation - genetics Genetic engineering Heart Heart - physiology Heart diseases Heart failure HeLa Cells Humans Hypertension Hypertrophy Hypoxia Hypoxia - metabolism Ischemia Isoproterenol Kidneys Kinases L-Lactate Dehydrogenase - metabolism Laboratory animals Major histocompatibility complex Male Medicine Mice Mice, Transgenic Myocardium - metabolism Protein folding Real-Time Polymerase Chain Reaction Receptors, Cell Surface - metabolism Renin Reperfusion Reperfusion Injury - metabolism RNA Rodents Smooth muscle Transgenic animals Transgenic mice |
| title | Cardiac function and architecture are maintained in a model of cardiorestricted overexpression of the prorenin-renin receptor |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T19%3A34%3A28IST&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=Cardiac%20function%20and%20architecture%20are%20maintained%20in%20a%20model%20of%20cardiorestricted%20overexpression%20of%20the%20prorenin-renin%20receptor&rft.jtitle=PloS%20one&rft.au=Mahmud,%20Hasan&rft.date=2014-02-25&rft.volume=9&rft.issue=2&rft.spage=e89929&rft.epage=e89929&rft.pages=e89929-e89929&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0089929&rft_dat=%3Cgale_plos_%3EA478792711%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=1977559169&rft_id=info:pmid/24587131&rft_galeid=A478792711&rft_doaj_id=oai_doaj_org_article_c4599e53a5514519b8058951b275fc41&rfr_iscdi=true |