Angiotensin II Type 2 Receptor Antagonizes Angiotensin II Type 1 Receptor–Mediated Cardiomyocyte Autophagy
Autophagy has emerged as an important process in the pathogenesis of cardiovascular diseases, but the proximal triggers for autophagy are unknown. Angiotensin II plays a central role in the pathogenesis of cardiac hypertrophy and heart failure. In this study, we used angiotensin II type 1 (AT1) and...
Gespeichert in:
| Veröffentlicht in: | Hypertension (Dallas, Tex. 1979) Tex. 1979), 2009-06, Vol.53 (6), p.1032-1040 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1040 |
|---|---|
| container_issue | 6 |
| container_start_page | 1032 |
| container_title | Hypertension (Dallas, Tex. 1979) |
| container_volume | 53 |
| creator | Porrello, Enzo R DʼAmore, Angelo Curl, Claire L Allen, Andrew M Harrap, Stephen B Thomas, Walter G Delbridge, Lea M.D |
| description | Autophagy has emerged as an important process in the pathogenesis of cardiovascular diseases, but the proximal triggers for autophagy are unknown. Angiotensin II plays a central role in the pathogenesis of cardiac hypertrophy and heart failure. In this study, we used angiotensin II type 1 (AT1) and type 2 (AT2) receptor–expressing adenoviruses in cultured neonatal cardiomyocytes to provide the first demonstration that neonatal cardiomyocyte autophagic activity is differentially modulated by AT1 and AT2 receptor subtypes. Angiotensin II stimulation (48 hours) of neonatal cardiomyocytes expressing the AT1 receptor alone (Ad-AT1; 10 multiplicities of infection) induced a significant increase in the number of HcRed-LC3 autophagosomes per cell (17.3±1.6 versus 33.3±4.1 autophagosomes per cell; P |
| doi_str_mv | 10.1161/HYPERTENSIONAHA.108.128488 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67281225</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>67281225</sourcerecordid><originalsourceid>FETCH-LOGICAL-c6096-f060a7284d17d74d57ee03a422c5965f2fb675ac1d069aaf8d05b2eeea7434f73</originalsourceid><addsrcrecordid>eNptkN2K1DAYhoMo7uzqLUgR9KxjkuavnpVhdAbWXVlH0KOQab7OVDtNTVKW7pH34B16JWaZYQUxEAIvz_eTB6GXBM8JEeTN6uvH5c1mefVpfX1Vrao5wWpOqGJKPUIzwinLGRfFYzTDpGR5SciXM3QewjeMCWNMPkVnKS8KqcgMdVW_a12EPrR9tl5nm2mAjGY3UMMQnc-qPpqd69s7CNn_UPKA_v756wPY1kSw2cJ427rD5OopQlaN0Q17s5ueoSeN6QI8P70X6PO75Waxyi-v368X1WVeC1yKvMECG5k-ZIm0klkuAXBhGKU1LwVvaLMVkpuaWCxKYxplMd9SADCSFayRxQV6few7ePdjhBD1oQ01dJ3pwY1Bi9ScUMoT-PYI1t6F4KHRg28Pxk-aYH3vWv_jOuVKH12n4henKeP2APZv6UluAl6dABNq0zXe9HUbHjhKeFEqdb8FO3K3rovgw_duvAWv92C6uNc4HUaFyinGZTKDcZ4uFcUfPTyaxA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67281225</pqid></control><display><type>article</type><title>Angiotensin II Type 2 Receptor Antagonizes Angiotensin II Type 1 Receptor–Mediated Cardiomyocyte Autophagy</title><source>MEDLINE</source><source>American Heart Association Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Journals@Ovid Complete</source><creator>Porrello, Enzo R ; DʼAmore, Angelo ; Curl, Claire L ; Allen, Andrew M ; Harrap, Stephen B ; Thomas, Walter G ; Delbridge, Lea M.D</creator><creatorcontrib>Porrello, Enzo R ; DʼAmore, Angelo ; Curl, Claire L ; Allen, Andrew M ; Harrap, Stephen B ; Thomas, Walter G ; Delbridge, Lea M.D</creatorcontrib><description>Autophagy has emerged as an important process in the pathogenesis of cardiovascular diseases, but the proximal triggers for autophagy are unknown. Angiotensin II plays a central role in the pathogenesis of cardiac hypertrophy and heart failure. In this study, we used angiotensin II type 1 (AT1) and type 2 (AT2) receptor–expressing adenoviruses in cultured neonatal cardiomyocytes to provide the first demonstration that neonatal cardiomyocyte autophagic activity is differentially modulated by AT1 and AT2 receptor subtypes. Angiotensin II stimulation (48 hours) of neonatal cardiomyocytes expressing the AT1 receptor alone (Ad-AT1; 10 multiplicities of infection) induced a significant increase in the number of HcRed-LC3 autophagosomes per cell (17.3±1.6 versus 33.3±4.1 autophagosomes per cell; P<0.05). Coexpression of a high ratio of AT2:AT1 (Ad-AT2:Ad-AT1 multiplicity of infection ratio20:5) receptors completely abrogated the AT1-mediated increase in autophagy (9.3±1.4 versus 33.3±4.1 autophagosomes per cell; P<0.05). Treatment with the AT2 receptor antagonist PD123319 did not reverse the AT2-mediated antiautophagic effect. AT1- and AT2-mediated autophagic responses were also assessed in cardiomyocytes from a genetic model that exhibits neonatal myocardial growth suppression. In these neonate myocyte cultures, AT1 receptor activation induced a marked increase in the number of myocytes containing cytoplasmic vacuoles compared with the control (22.7±4.1% versus 1.1±0.6%; P<0.001) and was characterized by a nonapoptotic autophagic phenotype. The incidence of cardiomyocyte autophagic vacuolization in this myocyte population decreased dramatically to only 0.4±0.2% in myocytes infected with a high ratio of Ad-AT2:Ad-AT1. This study provides the first description of reciprocal regulation of cardiomyocyte autophagic induction by the AT1 and AT2 receptor subtypes.</description><identifier>ISSN: 0194-911X</identifier><identifier>EISSN: 1524-4563</identifier><identifier>DOI: 10.1161/HYPERTENSIONAHA.108.128488</identifier><identifier>PMID: 19433781</identifier><identifier>CODEN: HPRTDN</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Adenoviridae - genetics ; Animals ; Animals, Newborn ; Arterial hypertension. Arterial hypotension ; Autophagy - genetics ; Autophagy - physiology ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cardiomegaly - metabolism ; Cardiomegaly - pathology ; Cells, Cultured ; Clinical manifestations. Epidemiology. Investigative techniques. Etiology ; Disease Models, Animal ; Female ; Gene Transfer Techniques ; Medical sciences ; Mitogen-Activated Protein Kinases - metabolism ; Myocytes, Cardiac - metabolism ; Myocytes, Cardiac - pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1 - genetics ; Receptor, Angiotensin, Type 1 - metabolism ; Receptor, Angiotensin, Type 2 - genetics ; Receptor, Angiotensin, Type 2 - metabolism ; Reference Values ; RNA, Messenger - analysis ; Sensitivity and Specificity</subject><ispartof>Hypertension (Dallas, Tex. 1979), 2009-06, Vol.53 (6), p.1032-1040</ispartof><rights>2009 American Heart Association, Inc.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6096-f060a7284d17d74d57ee03a422c5965f2fb675ac1d069aaf8d05b2eeea7434f73</citedby><cites>FETCH-LOGICAL-c6096-f060a7284d17d74d57ee03a422c5965f2fb675ac1d069aaf8d05b2eeea7434f73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,3691,27933,27934</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21539885$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19433781$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Porrello, Enzo R</creatorcontrib><creatorcontrib>DʼAmore, Angelo</creatorcontrib><creatorcontrib>Curl, Claire L</creatorcontrib><creatorcontrib>Allen, Andrew M</creatorcontrib><creatorcontrib>Harrap, Stephen B</creatorcontrib><creatorcontrib>Thomas, Walter G</creatorcontrib><creatorcontrib>Delbridge, Lea M.D</creatorcontrib><title>Angiotensin II Type 2 Receptor Antagonizes Angiotensin II Type 1 Receptor–Mediated Cardiomyocyte Autophagy</title><title>Hypertension (Dallas, Tex. 1979)</title><addtitle>Hypertension</addtitle><description>Autophagy has emerged as an important process in the pathogenesis of cardiovascular diseases, but the proximal triggers for autophagy are unknown. Angiotensin II plays a central role in the pathogenesis of cardiac hypertrophy and heart failure. In this study, we used angiotensin II type 1 (AT1) and type 2 (AT2) receptor–expressing adenoviruses in cultured neonatal cardiomyocytes to provide the first demonstration that neonatal cardiomyocyte autophagic activity is differentially modulated by AT1 and AT2 receptor subtypes. Angiotensin II stimulation (48 hours) of neonatal cardiomyocytes expressing the AT1 receptor alone (Ad-AT1; 10 multiplicities of infection) induced a significant increase in the number of HcRed-LC3 autophagosomes per cell (17.3±1.6 versus 33.3±4.1 autophagosomes per cell; P<0.05). Coexpression of a high ratio of AT2:AT1 (Ad-AT2:Ad-AT1 multiplicity of infection ratio20:5) receptors completely abrogated the AT1-mediated increase in autophagy (9.3±1.4 versus 33.3±4.1 autophagosomes per cell; P<0.05). Treatment with the AT2 receptor antagonist PD123319 did not reverse the AT2-mediated antiautophagic effect. AT1- and AT2-mediated autophagic responses were also assessed in cardiomyocytes from a genetic model that exhibits neonatal myocardial growth suppression. In these neonate myocyte cultures, AT1 receptor activation induced a marked increase in the number of myocytes containing cytoplasmic vacuoles compared with the control (22.7±4.1% versus 1.1±0.6%; P<0.001) and was characterized by a nonapoptotic autophagic phenotype. The incidence of cardiomyocyte autophagic vacuolization in this myocyte population decreased dramatically to only 0.4±0.2% in myocytes infected with a high ratio of Ad-AT2:Ad-AT1. This study provides the first description of reciprocal regulation of cardiomyocyte autophagic induction by the AT1 and AT2 receptor subtypes.</description><subject>Adenoviridae - genetics</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Arterial hypertension. Arterial hypotension</subject><subject>Autophagy - genetics</subject><subject>Autophagy - physiology</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cardiomegaly - metabolism</subject><subject>Cardiomegaly - pathology</subject><subject>Cells, Cultured</subject><subject>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Gene Transfer Techniques</subject><subject>Medical sciences</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Myocytes, Cardiac - pathology</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, Angiotensin, Type 1 - genetics</subject><subject>Receptor, Angiotensin, Type 1 - metabolism</subject><subject>Receptor, Angiotensin, Type 2 - genetics</subject><subject>Receptor, Angiotensin, Type 2 - metabolism</subject><subject>Reference Values</subject><subject>RNA, Messenger - analysis</subject><subject>Sensitivity and Specificity</subject><issn>0194-911X</issn><issn>1524-4563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkN2K1DAYhoMo7uzqLUgR9KxjkuavnpVhdAbWXVlH0KOQab7OVDtNTVKW7pH34B16JWaZYQUxEAIvz_eTB6GXBM8JEeTN6uvH5c1mefVpfX1Vrao5wWpOqGJKPUIzwinLGRfFYzTDpGR5SciXM3QewjeMCWNMPkVnKS8KqcgMdVW_a12EPrR9tl5nm2mAjGY3UMMQnc-qPpqd69s7CNn_UPKA_v756wPY1kSw2cJ427rD5OopQlaN0Q17s5ueoSeN6QI8P70X6PO75Waxyi-v368X1WVeC1yKvMECG5k-ZIm0klkuAXBhGKU1LwVvaLMVkpuaWCxKYxplMd9SADCSFayRxQV6few7ePdjhBD1oQ01dJ3pwY1Bi9ScUMoT-PYI1t6F4KHRg28Pxk-aYH3vWv_jOuVKH12n4henKeP2APZv6UluAl6dABNq0zXe9HUbHjhKeFEqdb8FO3K3rovgw_duvAWv92C6uNc4HUaFyinGZTKDcZ4uFcUfPTyaxA</recordid><startdate>200906</startdate><enddate>200906</enddate><creator>Porrello, Enzo R</creator><creator>DʼAmore, Angelo</creator><creator>Curl, Claire L</creator><creator>Allen, Andrew M</creator><creator>Harrap, Stephen B</creator><creator>Thomas, Walter G</creator><creator>Delbridge, Lea M.D</creator><general>American Heart Association, Inc</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><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></search><sort><creationdate>200906</creationdate><title>Angiotensin II Type 2 Receptor Antagonizes Angiotensin II Type 1 Receptor–Mediated Cardiomyocyte Autophagy</title><author>Porrello, Enzo R ; DʼAmore, Angelo ; Curl, Claire L ; Allen, Andrew M ; Harrap, Stephen B ; Thomas, Walter G ; Delbridge, Lea M.D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6096-f060a7284d17d74d57ee03a422c5965f2fb675ac1d069aaf8d05b2eeea7434f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adenoviridae - genetics</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Arterial hypertension. Arterial hypotension</topic><topic>Autophagy - genetics</topic><topic>Autophagy - physiology</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cardiomegaly - metabolism</topic><topic>Cardiomegaly - pathology</topic><topic>Cells, Cultured</topic><topic>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Gene Transfer Techniques</topic><topic>Medical sciences</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Myocytes, Cardiac - pathology</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, Angiotensin, Type 1 - genetics</topic><topic>Receptor, Angiotensin, Type 1 - metabolism</topic><topic>Receptor, Angiotensin, Type 2 - genetics</topic><topic>Receptor, Angiotensin, Type 2 - metabolism</topic><topic>Reference Values</topic><topic>RNA, Messenger - analysis</topic><topic>Sensitivity and Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Porrello, Enzo R</creatorcontrib><creatorcontrib>DʼAmore, Angelo</creatorcontrib><creatorcontrib>Curl, Claire L</creatorcontrib><creatorcontrib>Allen, Andrew M</creatorcontrib><creatorcontrib>Harrap, Stephen B</creatorcontrib><creatorcontrib>Thomas, Walter G</creatorcontrib><creatorcontrib>Delbridge, Lea M.D</creatorcontrib><collection>Pascal-Francis</collection><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><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Porrello, Enzo R</au><au>DʼAmore, Angelo</au><au>Curl, Claire L</au><au>Allen, Andrew M</au><au>Harrap, Stephen B</au><au>Thomas, Walter G</au><au>Delbridge, Lea M.D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Angiotensin II Type 2 Receptor Antagonizes Angiotensin II Type 1 Receptor–Mediated Cardiomyocyte Autophagy</atitle><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle><addtitle>Hypertension</addtitle><date>2009-06</date><risdate>2009</risdate><volume>53</volume><issue>6</issue><spage>1032</spage><epage>1040</epage><pages>1032-1040</pages><issn>0194-911X</issn><eissn>1524-4563</eissn><coden>HPRTDN</coden><abstract>Autophagy has emerged as an important process in the pathogenesis of cardiovascular diseases, but the proximal triggers for autophagy are unknown. Angiotensin II plays a central role in the pathogenesis of cardiac hypertrophy and heart failure. In this study, we used angiotensin II type 1 (AT1) and type 2 (AT2) receptor–expressing adenoviruses in cultured neonatal cardiomyocytes to provide the first demonstration that neonatal cardiomyocyte autophagic activity is differentially modulated by AT1 and AT2 receptor subtypes. Angiotensin II stimulation (48 hours) of neonatal cardiomyocytes expressing the AT1 receptor alone (Ad-AT1; 10 multiplicities of infection) induced a significant increase in the number of HcRed-LC3 autophagosomes per cell (17.3±1.6 versus 33.3±4.1 autophagosomes per cell; P<0.05). Coexpression of a high ratio of AT2:AT1 (Ad-AT2:Ad-AT1 multiplicity of infection ratio20:5) receptors completely abrogated the AT1-mediated increase in autophagy (9.3±1.4 versus 33.3±4.1 autophagosomes per cell; P<0.05). Treatment with the AT2 receptor antagonist PD123319 did not reverse the AT2-mediated antiautophagic effect. AT1- and AT2-mediated autophagic responses were also assessed in cardiomyocytes from a genetic model that exhibits neonatal myocardial growth suppression. In these neonate myocyte cultures, AT1 receptor activation induced a marked increase in the number of myocytes containing cytoplasmic vacuoles compared with the control (22.7±4.1% versus 1.1±0.6%; P<0.001) and was characterized by a nonapoptotic autophagic phenotype. The incidence of cardiomyocyte autophagic vacuolization in this myocyte population decreased dramatically to only 0.4±0.2% in myocytes infected with a high ratio of Ad-AT2:Ad-AT1. This study provides the first description of reciprocal regulation of cardiomyocyte autophagic induction by the AT1 and AT2 receptor subtypes.</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>19433781</pmid><doi>10.1161/HYPERTENSIONAHA.108.128488</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0194-911X |
| ispartof | Hypertension (Dallas, Tex. 1979), 2009-06, Vol.53 (6), p.1032-1040 |
| issn | 0194-911X 1524-4563 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67281225 |
| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Adenoviridae - genetics Animals Animals, Newborn Arterial hypertension. Arterial hypotension Autophagy - genetics Autophagy - physiology Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cardiomegaly - metabolism Cardiomegaly - pathology Cells, Cultured Clinical manifestations. Epidemiology. Investigative techniques. Etiology Disease Models, Animal Female Gene Transfer Techniques Medical sciences Mitogen-Activated Protein Kinases - metabolism Myocytes, Cardiac - metabolism Myocytes, Cardiac - pathology Random Allocation Rats Rats, Sprague-Dawley Receptor, Angiotensin, Type 1 - genetics Receptor, Angiotensin, Type 1 - metabolism Receptor, Angiotensin, Type 2 - genetics Receptor, Angiotensin, Type 2 - metabolism Reference Values RNA, Messenger - analysis Sensitivity and Specificity |
| title | Angiotensin II Type 2 Receptor Antagonizes Angiotensin II Type 1 Receptor–Mediated Cardiomyocyte Autophagy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-02T09%3A55%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Angiotensin%20II%20Type%202%20Receptor%20Antagonizes%20Angiotensin%20II%20Type%201%20Receptor%E2%80%93Mediated%20Cardiomyocyte%20Autophagy&rft.jtitle=Hypertension%20(Dallas,%20Tex.%201979)&rft.au=Porrello,%20Enzo%20R&rft.date=2009-06&rft.volume=53&rft.issue=6&rft.spage=1032&rft.epage=1040&rft.pages=1032-1040&rft.issn=0194-911X&rft.eissn=1524-4563&rft.coden=HPRTDN&rft_id=info:doi/10.1161/HYPERTENSIONAHA.108.128488&rft_dat=%3Cproquest_cross%3E67281225%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=67281225&rft_id=info:pmid/19433781&rfr_iscdi=true |