Anthracycline-Induced Atrial Structural and Electrical Remodeling Characterizes Early Cardiotoxicity and Contributes to Atrial Conductive Instability and Dysfunction
Cancer patients treated with anthracyclines are susceptible to atrial fibrillation (AF), while the mechanisms remain unclear. Due to sudden and unpredictable features, prediction of anthracycline-induced AF at early phase is difficult. Clinically, we tested whether anthracycline-induced early atrial...
Gespeichert in:
| Veröffentlicht in: | Antioxidants & redox signaling 2022-07, Vol.37 (1-3), p.19-39 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 39 |
|---|---|
| container_issue | 1-3 |
| container_start_page | 19 |
| container_title | Antioxidants & redox signaling |
| container_volume | 37 |
| creator | Tan, Ruopeng Cong, Tao Xu, Guiwen Hao, Zhujing Liao, Jiawei Xie, Yunpeng Lin, Yajuan Yang, Xiaolei Li, Qingsong Liu, Yang Xia, Yun-Long |
| description | Cancer patients treated with anthracyclines are susceptible to atrial fibrillation (AF), while the mechanisms remain unclear. Due to sudden and unpredictable features, prediction of anthracycline-induced AF at early phase is difficult. Clinically, we tested whether anthracycline-induced early atrial remodeling in patients could be detected by echocardiography. Experimentally, we investigated the mechanisms of doxorubicin-induced atrial remodeling and AF in mice, and the protective effects of dexrazoxane and antioxidants.
Postsurgery breast cancer patients with an anthracycline-containing or anthracycline exclusion regimen were recruited for echocardiography before chemotherapy, and 3 and 6 months after chemotherapy. Mice were injected with doxorubicin or vehicle (5 mg/kg/week, 4 weeks), and left atrial diameter, electrical transmission, and AF inducibility were measured. Meanwhile, the level of reactive oxygen species (ROS), activity of antioxidant enzymes, cardiomyocyte size, vacuolization, inflammation, and fibrosis were also measured in mouse atria. The therapeutic effects of dexrazoxane and antioxidants on doxorubicin-induced changes in the aforementioned parameters were also determined. While ventricular parameters and functions were unchanged in cancer patients receiving anthracyclines before and after chemotherapy, left atrial reservoir and conduit function were decreased at 3 months postchemotherapy
prechemotherapy. Doxorubicin-induced susceptibility to AF occurred in mice before onset of ventricular dysfunction. Doxorubicin-induced AF was
inducing structural remodeling (cardiomyocyte death, hypotrophy, and vacuolization) and electrical remodeling (reduction and redistribution of connexin 43) in atria, which was effectively prevented by dexrazoxane or antioxidants through inhibiting ROS generation or enhancing ROS elimination.
AF inducibility was induced after doxorubicin injection, which can be inhibited by repressing the ROS level. The Clinical Trial Registration number is PJ-KS-KY-2019-73. |
| doi_str_mv | 10.1089/ars.2021.0002 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2623323461</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2623323461</sourcerecordid><originalsourceid>FETCH-LOGICAL-c321t-496a854838d6bb9cffe8cd1b00923217aaf93bae2169f07444a1a00b6e4ac05e3</originalsourceid><addsrcrecordid>eNpdkUtv1TAQhS1ERUthyRZFYsMmt37FSZZX4VKuVKkSj3U0cSbUVa5d_KgI_4f_WYf2suhqZjzfOWPpEPKO0Q2jTXsBPmw45WxDKeUvyBmrqrqsa6Zerj0XJW2UPCWvQ7hdCcboK3IqKtqwWvIz8ndr440HvejZWCz3dkwax2IbvYG5-BZ90jH53IIdi92MOi90Hr_iwY2YNT-L7gayQURv_mAoduDnpejAj8ZF99toE5d_4s7ZrB1SzFB0xwv5NV-M5h6LvQ0RBjMfBZ-WMCWbd86-IScTzAHfPtVz8uPz7nv3pby6vtx326tSC85iKVsFTSUb0YxqGFo9TdjokQ2UtjwDNcDUigGQM9VOtJZSAgNKB4USNK1QnJOPj7533v1KGGJ_MEHjPINFl0LPFReCC6lYRj88Q29d8jb_LlON4lVL2ypT5SOlvQvB49TfeXMAv_SM9mt-fc6vX_Pr13Qy__7JNQ0HHP_Tx8DEA0gBmbw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2686259095</pqid></control><display><type>article</type><title>Anthracycline-Induced Atrial Structural and Electrical Remodeling Characterizes Early Cardiotoxicity and Contributes to Atrial Conductive Instability and Dysfunction</title><source>Alma/SFX Local Collection</source><creator>Tan, Ruopeng ; Cong, Tao ; Xu, Guiwen ; Hao, Zhujing ; Liao, Jiawei ; Xie, Yunpeng ; Lin, Yajuan ; Yang, Xiaolei ; Li, Qingsong ; Liu, Yang ; Xia, Yun-Long</creator><creatorcontrib>Tan, Ruopeng ; Cong, Tao ; Xu, Guiwen ; Hao, Zhujing ; Liao, Jiawei ; Xie, Yunpeng ; Lin, Yajuan ; Yang, Xiaolei ; Li, Qingsong ; Liu, Yang ; Xia, Yun-Long</creatorcontrib><description>Cancer patients treated with anthracyclines are susceptible to atrial fibrillation (AF), while the mechanisms remain unclear. Due to sudden and unpredictable features, prediction of anthracycline-induced AF at early phase is difficult. Clinically, we tested whether anthracycline-induced early atrial remodeling in patients could be detected by echocardiography. Experimentally, we investigated the mechanisms of doxorubicin-induced atrial remodeling and AF in mice, and the protective effects of dexrazoxane and antioxidants.
Postsurgery breast cancer patients with an anthracycline-containing or anthracycline exclusion regimen were recruited for echocardiography before chemotherapy, and 3 and 6 months after chemotherapy. Mice were injected with doxorubicin or vehicle (5 mg/kg/week, 4 weeks), and left atrial diameter, electrical transmission, and AF inducibility were measured. Meanwhile, the level of reactive oxygen species (ROS), activity of antioxidant enzymes, cardiomyocyte size, vacuolization, inflammation, and fibrosis were also measured in mouse atria. The therapeutic effects of dexrazoxane and antioxidants on doxorubicin-induced changes in the aforementioned parameters were also determined. While ventricular parameters and functions were unchanged in cancer patients receiving anthracyclines before and after chemotherapy, left atrial reservoir and conduit function were decreased at 3 months postchemotherapy
prechemotherapy. Doxorubicin-induced susceptibility to AF occurred in mice before onset of ventricular dysfunction. Doxorubicin-induced AF was
inducing structural remodeling (cardiomyocyte death, hypotrophy, and vacuolization) and electrical remodeling (reduction and redistribution of connexin 43) in atria, which was effectively prevented by dexrazoxane or antioxidants through inhibiting ROS generation or enhancing ROS elimination.
AF inducibility was induced after doxorubicin injection, which can be inhibited by repressing the ROS level. The Clinical Trial Registration number is PJ-KS-KY-2019-73.</description><identifier>ISSN: 1523-0864</identifier><identifier>EISSN: 1557-7716</identifier><identifier>DOI: 10.1089/ars.2021.0002</identifier><identifier>PMID: 35081742</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Anthracycline ; Antioxidants ; Atria ; Breast cancer ; Cancer ; Cardiomyocytes ; Cardiotoxicity ; Chemotherapy ; Connexin 43 ; Diameters ; Doxorubicin ; Echocardiography ; Electrical transmission ; Fibrillation ; Fibrosis ; Parameters ; Patients ; Razoxane ; Reactive oxygen species ; Ventricle</subject><ispartof>Antioxidants & redox signaling, 2022-07, Vol.37 (1-3), p.19-39</ispartof><rights>Copyright Mary Ann Liebert, Inc. Jul 1, 2022</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c321t-496a854838d6bb9cffe8cd1b00923217aaf93bae2169f07444a1a00b6e4ac05e3</citedby><cites>FETCH-LOGICAL-c321t-496a854838d6bb9cffe8cd1b00923217aaf93bae2169f07444a1a00b6e4ac05e3</cites><orcidid>0000-0001-9331-1083 ; 0000-0002-8972-1466</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35081742$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tan, Ruopeng</creatorcontrib><creatorcontrib>Cong, Tao</creatorcontrib><creatorcontrib>Xu, Guiwen</creatorcontrib><creatorcontrib>Hao, Zhujing</creatorcontrib><creatorcontrib>Liao, Jiawei</creatorcontrib><creatorcontrib>Xie, Yunpeng</creatorcontrib><creatorcontrib>Lin, Yajuan</creatorcontrib><creatorcontrib>Yang, Xiaolei</creatorcontrib><creatorcontrib>Li, Qingsong</creatorcontrib><creatorcontrib>Liu, Yang</creatorcontrib><creatorcontrib>Xia, Yun-Long</creatorcontrib><title>Anthracycline-Induced Atrial Structural and Electrical Remodeling Characterizes Early Cardiotoxicity and Contributes to Atrial Conductive Instability and Dysfunction</title><title>Antioxidants & redox signaling</title><addtitle>Antioxid Redox Signal</addtitle><description>Cancer patients treated with anthracyclines are susceptible to atrial fibrillation (AF), while the mechanisms remain unclear. Due to sudden and unpredictable features, prediction of anthracycline-induced AF at early phase is difficult. Clinically, we tested whether anthracycline-induced early atrial remodeling in patients could be detected by echocardiography. Experimentally, we investigated the mechanisms of doxorubicin-induced atrial remodeling and AF in mice, and the protective effects of dexrazoxane and antioxidants.
Postsurgery breast cancer patients with an anthracycline-containing or anthracycline exclusion regimen were recruited for echocardiography before chemotherapy, and 3 and 6 months after chemotherapy. Mice were injected with doxorubicin or vehicle (5 mg/kg/week, 4 weeks), and left atrial diameter, electrical transmission, and AF inducibility were measured. Meanwhile, the level of reactive oxygen species (ROS), activity of antioxidant enzymes, cardiomyocyte size, vacuolization, inflammation, and fibrosis were also measured in mouse atria. The therapeutic effects of dexrazoxane and antioxidants on doxorubicin-induced changes in the aforementioned parameters were also determined. While ventricular parameters and functions were unchanged in cancer patients receiving anthracyclines before and after chemotherapy, left atrial reservoir and conduit function were decreased at 3 months postchemotherapy
prechemotherapy. Doxorubicin-induced susceptibility to AF occurred in mice before onset of ventricular dysfunction. Doxorubicin-induced AF was
inducing structural remodeling (cardiomyocyte death, hypotrophy, and vacuolization) and electrical remodeling (reduction and redistribution of connexin 43) in atria, which was effectively prevented by dexrazoxane or antioxidants through inhibiting ROS generation or enhancing ROS elimination.
AF inducibility was induced after doxorubicin injection, which can be inhibited by repressing the ROS level. The Clinical Trial Registration number is PJ-KS-KY-2019-73.</description><subject>Anthracycline</subject><subject>Antioxidants</subject><subject>Atria</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cardiomyocytes</subject><subject>Cardiotoxicity</subject><subject>Chemotherapy</subject><subject>Connexin 43</subject><subject>Diameters</subject><subject>Doxorubicin</subject><subject>Echocardiography</subject><subject>Electrical transmission</subject><subject>Fibrillation</subject><subject>Fibrosis</subject><subject>Parameters</subject><subject>Patients</subject><subject>Razoxane</subject><subject>Reactive oxygen species</subject><subject>Ventricle</subject><issn>1523-0864</issn><issn>1557-7716</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNpdkUtv1TAQhS1ERUthyRZFYsMmt37FSZZX4VKuVKkSj3U0cSbUVa5d_KgI_4f_WYf2suhqZjzfOWPpEPKO0Q2jTXsBPmw45WxDKeUvyBmrqrqsa6Zerj0XJW2UPCWvQ7hdCcboK3IqKtqwWvIz8ndr440HvejZWCz3dkwax2IbvYG5-BZ90jH53IIdi92MOi90Hr_iwY2YNT-L7gayQURv_mAoduDnpejAj8ZF99toE5d_4s7ZrB1SzFB0xwv5NV-M5h6LvQ0RBjMfBZ-WMCWbd86-IScTzAHfPtVz8uPz7nv3pby6vtx326tSC85iKVsFTSUb0YxqGFo9TdjokQ2UtjwDNcDUigGQM9VOtJZSAgNKB4USNK1QnJOPj7533v1KGGJ_MEHjPINFl0LPFReCC6lYRj88Q29d8jb_LlON4lVL2ypT5SOlvQvB49TfeXMAv_SM9mt-fc6vX_Pr13Qy__7JNQ0HHP_Tx8DEA0gBmbw</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Tan, Ruopeng</creator><creator>Cong, Tao</creator><creator>Xu, Guiwen</creator><creator>Hao, Zhujing</creator><creator>Liao, Jiawei</creator><creator>Xie, Yunpeng</creator><creator>Lin, Yajuan</creator><creator>Yang, Xiaolei</creator><creator>Li, Qingsong</creator><creator>Liu, Yang</creator><creator>Xia, Yun-Long</creator><general>Mary Ann Liebert, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9331-1083</orcidid><orcidid>https://orcid.org/0000-0002-8972-1466</orcidid></search><sort><creationdate>20220701</creationdate><title>Anthracycline-Induced Atrial Structural and Electrical Remodeling Characterizes Early Cardiotoxicity and Contributes to Atrial Conductive Instability and Dysfunction</title><author>Tan, Ruopeng ; Cong, Tao ; Xu, Guiwen ; Hao, Zhujing ; Liao, Jiawei ; Xie, Yunpeng ; Lin, Yajuan ; Yang, Xiaolei ; Li, Qingsong ; Liu, Yang ; Xia, Yun-Long</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c321t-496a854838d6bb9cffe8cd1b00923217aaf93bae2169f07444a1a00b6e4ac05e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Anthracycline</topic><topic>Antioxidants</topic><topic>Atria</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cardiomyocytes</topic><topic>Cardiotoxicity</topic><topic>Chemotherapy</topic><topic>Connexin 43</topic><topic>Diameters</topic><topic>Doxorubicin</topic><topic>Echocardiography</topic><topic>Electrical transmission</topic><topic>Fibrillation</topic><topic>Fibrosis</topic><topic>Parameters</topic><topic>Patients</topic><topic>Razoxane</topic><topic>Reactive oxygen species</topic><topic>Ventricle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tan, Ruopeng</creatorcontrib><creatorcontrib>Cong, Tao</creatorcontrib><creatorcontrib>Xu, Guiwen</creatorcontrib><creatorcontrib>Hao, Zhujing</creatorcontrib><creatorcontrib>Liao, Jiawei</creatorcontrib><creatorcontrib>Xie, Yunpeng</creatorcontrib><creatorcontrib>Lin, Yajuan</creatorcontrib><creatorcontrib>Yang, Xiaolei</creatorcontrib><creatorcontrib>Li, Qingsong</creatorcontrib><creatorcontrib>Liu, Yang</creatorcontrib><creatorcontrib>Xia, Yun-Long</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Antioxidants & redox signaling</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tan, Ruopeng</au><au>Cong, Tao</au><au>Xu, Guiwen</au><au>Hao, Zhujing</au><au>Liao, Jiawei</au><au>Xie, Yunpeng</au><au>Lin, Yajuan</au><au>Yang, Xiaolei</au><au>Li, Qingsong</au><au>Liu, Yang</au><au>Xia, Yun-Long</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anthracycline-Induced Atrial Structural and Electrical Remodeling Characterizes Early Cardiotoxicity and Contributes to Atrial Conductive Instability and Dysfunction</atitle><jtitle>Antioxidants & redox signaling</jtitle><addtitle>Antioxid Redox Signal</addtitle><date>2022-07-01</date><risdate>2022</risdate><volume>37</volume><issue>1-3</issue><spage>19</spage><epage>39</epage><pages>19-39</pages><issn>1523-0864</issn><eissn>1557-7716</eissn><abstract>Cancer patients treated with anthracyclines are susceptible to atrial fibrillation (AF), while the mechanisms remain unclear. Due to sudden and unpredictable features, prediction of anthracycline-induced AF at early phase is difficult. Clinically, we tested whether anthracycline-induced early atrial remodeling in patients could be detected by echocardiography. Experimentally, we investigated the mechanisms of doxorubicin-induced atrial remodeling and AF in mice, and the protective effects of dexrazoxane and antioxidants.
Postsurgery breast cancer patients with an anthracycline-containing or anthracycline exclusion regimen were recruited for echocardiography before chemotherapy, and 3 and 6 months after chemotherapy. Mice were injected with doxorubicin or vehicle (5 mg/kg/week, 4 weeks), and left atrial diameter, electrical transmission, and AF inducibility were measured. Meanwhile, the level of reactive oxygen species (ROS), activity of antioxidant enzymes, cardiomyocyte size, vacuolization, inflammation, and fibrosis were also measured in mouse atria. The therapeutic effects of dexrazoxane and antioxidants on doxorubicin-induced changes in the aforementioned parameters were also determined. While ventricular parameters and functions were unchanged in cancer patients receiving anthracyclines before and after chemotherapy, left atrial reservoir and conduit function were decreased at 3 months postchemotherapy
prechemotherapy. Doxorubicin-induced susceptibility to AF occurred in mice before onset of ventricular dysfunction. Doxorubicin-induced AF was
inducing structural remodeling (cardiomyocyte death, hypotrophy, and vacuolization) and electrical remodeling (reduction and redistribution of connexin 43) in atria, which was effectively prevented by dexrazoxane or antioxidants through inhibiting ROS generation or enhancing ROS elimination.
AF inducibility was induced after doxorubicin injection, which can be inhibited by repressing the ROS level. The Clinical Trial Registration number is PJ-KS-KY-2019-73.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>35081742</pmid><doi>10.1089/ars.2021.0002</doi><tpages>21</tpages><orcidid>https://orcid.org/0000-0001-9331-1083</orcidid><orcidid>https://orcid.org/0000-0002-8972-1466</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1523-0864 |
| ispartof | Antioxidants & redox signaling, 2022-07, Vol.37 (1-3), p.19-39 |
| issn | 1523-0864 1557-7716 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2623323461 |
| source | Alma/SFX Local Collection |
| subjects | Anthracycline Antioxidants Atria Breast cancer Cancer Cardiomyocytes Cardiotoxicity Chemotherapy Connexin 43 Diameters Doxorubicin Echocardiography Electrical transmission Fibrillation Fibrosis Parameters Patients Razoxane Reactive oxygen species Ventricle |
| title | Anthracycline-Induced Atrial Structural and Electrical Remodeling Characterizes Early Cardiotoxicity and Contributes to Atrial Conductive Instability and Dysfunction |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T02%3A51%3A10IST&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=Anthracycline-Induced%20Atrial%20Structural%20and%20Electrical%20Remodeling%20Characterizes%20Early%20Cardiotoxicity%20and%20Contributes%20to%20Atrial%20Conductive%20Instability%20and%20Dysfunction&rft.jtitle=Antioxidants%20&%20redox%20signaling&rft.au=Tan,%20Ruopeng&rft.date=2022-07-01&rft.volume=37&rft.issue=1-3&rft.spage=19&rft.epage=39&rft.pages=19-39&rft.issn=1523-0864&rft.eissn=1557-7716&rft_id=info:doi/10.1089/ars.2021.0002&rft_dat=%3Cproquest_cross%3E2623323461%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=2686259095&rft_id=info:pmid/35081742&rfr_iscdi=true |