Molecular mechanisms of anthracycline induced cardiotoxicity: Zebrafish come into play
Anthracyclines are among the most potent chemotherapeutics; however, cardiotoxicity significantly restricts their use. Indeed, anthracycline-induced cardiotoxicity (AIC) fares among the worst types of cardiomyopathy, and may only slowly and partially respond to standard heart failure therapies inclu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1080299/full |
| _version_ | 1811155453361520640 |
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| author | Maryam Moossavi Maryam Moossavi Xiaoguang Lu Xiaoguang Lu Xiaoguang Lu Joerg Herrmann Xiaolei Xu Xiaolei Xu |
| author_facet | Maryam Moossavi Maryam Moossavi Xiaoguang Lu Xiaoguang Lu Xiaoguang Lu Joerg Herrmann Xiaolei Xu Xiaolei Xu |
| author_sort | Maryam Moossavi |
| collection | DOAJ |
| description | Anthracyclines are among the most potent chemotherapeutics; however, cardiotoxicity significantly restricts their use. Indeed, anthracycline-induced cardiotoxicity (AIC) fares among the worst types of cardiomyopathy, and may only slowly and partially respond to standard heart failure therapies including β-blockers and ACE inhibitors. No therapy specifically designed to treat anthracycline cardiomyopathy at present, and neither is it known if any such strategy could be developed. To address this gap and to elucidate the molecular basis of AIC with a therapeutic goal in mind, zebrafish has been introduced as an in vivo vertebrate model about a decade ago. Here, we first review our current understanding of the basic molecular and biochemical mechanisms of AIC, and then the contribution of zebrafish to the AIC field. We summarize the generation of embryonic zebrafish AIC models (eAIC) and their use for chemical screening and assessment of genetic modifiers, and then the generation of adult zebrafish AIC models (aAIC) and their use for discovering genetic modifiers via forward mutagenesis screening, deciphering spatial-temporal-specific mechanisms of modifier genes, and prioritizing therapeutic compounds via chemical genetic tools. Several therapeutic target genes and related therapies have emerged, including a retinoic acid (RA)-based therapy for the early phase of AIC and an autophagy-based therapy that, for the first time, is able to reverse cardiac dysfunction in the late phase of AIC. We conclude that zebrafish is becoming an important in vivo model that would accelerate both mechanistic studies and therapeutic development of AIC. |
| first_indexed | 2024-04-10T04:34:14Z |
| format | Article |
| id | doaj.art-c8bae8d158844bed84882abd7bab43ab |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-10T04:34:14Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-c8bae8d158844bed84882abd7bab43ab2023-03-10T05:02:03ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-03-011010.3389/fcvm.2023.10802991080299Molecular mechanisms of anthracycline induced cardiotoxicity: Zebrafish come into playMaryam Moossavi0Maryam Moossavi1Xiaoguang Lu2Xiaoguang Lu3Xiaoguang Lu4Joerg Herrmann5Xiaolei Xu6Xiaolei Xu7Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United StatesDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United StatesSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United StatesDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United StatesAnthracyclines are among the most potent chemotherapeutics; however, cardiotoxicity significantly restricts their use. Indeed, anthracycline-induced cardiotoxicity (AIC) fares among the worst types of cardiomyopathy, and may only slowly and partially respond to standard heart failure therapies including β-blockers and ACE inhibitors. No therapy specifically designed to treat anthracycline cardiomyopathy at present, and neither is it known if any such strategy could be developed. To address this gap and to elucidate the molecular basis of AIC with a therapeutic goal in mind, zebrafish has been introduced as an in vivo vertebrate model about a decade ago. Here, we first review our current understanding of the basic molecular and biochemical mechanisms of AIC, and then the contribution of zebrafish to the AIC field. We summarize the generation of embryonic zebrafish AIC models (eAIC) and their use for chemical screening and assessment of genetic modifiers, and then the generation of adult zebrafish AIC models (aAIC) and their use for discovering genetic modifiers via forward mutagenesis screening, deciphering spatial-temporal-specific mechanisms of modifier genes, and prioritizing therapeutic compounds via chemical genetic tools. Several therapeutic target genes and related therapies have emerged, including a retinoic acid (RA)-based therapy for the early phase of AIC and an autophagy-based therapy that, for the first time, is able to reverse cardiac dysfunction in the late phase of AIC. We conclude that zebrafish is becoming an important in vivo model that would accelerate both mechanistic studies and therapeutic development of AIC.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1080299/fullzebrafishanthracyclinescardiotoxicitymitochondriaapoptosis |
| spellingShingle | Maryam Moossavi Maryam Moossavi Xiaoguang Lu Xiaoguang Lu Xiaoguang Lu Joerg Herrmann Xiaolei Xu Xiaolei Xu Molecular mechanisms of anthracycline induced cardiotoxicity: Zebrafish come into play Frontiers in Cardiovascular Medicine zebrafish anthracyclines cardiotoxicity mitochondria apoptosis |
| title | Molecular mechanisms of anthracycline induced cardiotoxicity: Zebrafish come into play |
| title_full | Molecular mechanisms of anthracycline induced cardiotoxicity: Zebrafish come into play |
| title_fullStr | Molecular mechanisms of anthracycline induced cardiotoxicity: Zebrafish come into play |
| title_full_unstemmed | Molecular mechanisms of anthracycline induced cardiotoxicity: Zebrafish come into play |
| title_short | Molecular mechanisms of anthracycline induced cardiotoxicity: Zebrafish come into play |
| title_sort | molecular mechanisms of anthracycline induced cardiotoxicity zebrafish come into play |
| topic | zebrafish anthracyclines cardiotoxicity mitochondria apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1080299/full |
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