Infiltrating macrophages amplify doxorubicin-induced cardiac damage : role of catecholamines
© 2023. The Author(s)..
BACKGROUND: The functional contribution of non-myocyte cardiac cells, such as inflammatory cells, in the setup of heart failure in response to doxorubicin (Dox) is recently becoming of growing interest.
OBJECTIVES: The study aims to evaluate the role of macrophages in cardiac damage elicited by Dox treatment.
METHODS: C57BL/6 mice were treated with one intraperitoneal injection of Dox (20 mg/kg) and followed up for 5 days by cardiac ultrasounds (CUS), histological, and flow cytometry evaluations. We also tested the impact of Dox in macrophage-depleted mice. Rat cardiomyoblasts were directly treated with Dox (D-Dox) or with a conditioned medium from cultured murine macrophages treated with Dox (M-Dox).
RESULTS: In response to Dox, macrophage infiltration preceded cardiac damage. Macrophage depletion prevents Dox-induced damage, suggesting a key role of these cells in promoting cardiotoxicity. To evaluate the crosstalk between macrophages and cardiac cells in response to DOX, we compared the effects of D-Dox and M-Dox in vitro. Cell vitality was lower in cardiomyoblasts and apoptosis was higher in response to M-Dox compared with D-Dox. These events were linked to p53-induced mitochondria morphology, function, and autophagy alterations. We identify a mechanistic role of catecholamines released by Dox-activated macrophages that lead to mitochondrial apoptosis of cardiac cells through β-AR stimulation.
CONCLUSIONS: Our data indicate that crosstalk between macrophages and cardiac cells participates in cardiac damage in response to Dox.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:80 |
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| Enthalten in: |
Cellular and molecular life sciences : CMLS - 80(2023), 11 vom: 11. Okt., Seite 323 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gambardella, Jessica [VerfasserIn] |
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| Links: |
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| Themen: |
β-AR |
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| Anmerkungen: |
Date Completed 13.10.2023 Date Revised 11.11.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00018-023-04922-5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363125396 |
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| 245 | 1 | 0 | |a Infiltrating macrophages amplify doxorubicin-induced cardiac damage |b role of catecholamines |
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| 500 | |a Date Revised 11.11.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a BACKGROUND: The functional contribution of non-myocyte cardiac cells, such as inflammatory cells, in the setup of heart failure in response to doxorubicin (Dox) is recently becoming of growing interest | ||
| 520 | |a OBJECTIVES: The study aims to evaluate the role of macrophages in cardiac damage elicited by Dox treatment | ||
| 520 | |a METHODS: C57BL/6 mice were treated with one intraperitoneal injection of Dox (20 mg/kg) and followed up for 5 days by cardiac ultrasounds (CUS), histological, and flow cytometry evaluations. We also tested the impact of Dox in macrophage-depleted mice. Rat cardiomyoblasts were directly treated with Dox (D-Dox) or with a conditioned medium from cultured murine macrophages treated with Dox (M-Dox) | ||
| 520 | |a RESULTS: In response to Dox, macrophage infiltration preceded cardiac damage. Macrophage depletion prevents Dox-induced damage, suggesting a key role of these cells in promoting cardiotoxicity. To evaluate the crosstalk between macrophages and cardiac cells in response to DOX, we compared the effects of D-Dox and M-Dox in vitro. Cell vitality was lower in cardiomyoblasts and apoptosis was higher in response to M-Dox compared with D-Dox. These events were linked to p53-induced mitochondria morphology, function, and autophagy alterations. We identify a mechanistic role of catecholamines released by Dox-activated macrophages that lead to mitochondrial apoptosis of cardiac cells through β-AR stimulation | ||
| 520 | |a CONCLUSIONS: Our data indicate that crosstalk between macrophages and cardiac cells participates in cardiac damage in response to Dox | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Catecholamines | |
| 650 | 4 | |a Doxorubicin | |
| 650 | 4 | |a Macrophages | |
| 650 | 4 | |a Mitochondria | |
| 650 | 4 | |a Mitophagy | |
| 650 | 4 | |a p53 | |
| 650 | 4 | |a β-AR | |
| 650 | 7 | |a Catecholamines |2 NLM | |
| 650 | 7 | |a Doxorubicin |2 NLM | |
| 650 | 7 | |a 80168379AG |2 NLM | |
| 700 | 1 | |a Santulli, Gaetano |e verfasserin |4 aut | |
| 700 | 1 | |a Fiordelisi, Antonella |e verfasserin |4 aut | |
| 700 | 1 | |a Cerasuolo, Federica Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xujun |e verfasserin |4 aut | |
| 700 | 1 | |a Prevete, Nella |e verfasserin |4 aut | |
| 700 | 1 | |a Sommella, Eduardo |e verfasserin |4 aut | |
| 700 | 1 | |a Avvisato, Roberta |e verfasserin |4 aut | |
| 700 | 1 | |a Buonaiuto, Antonietta |e verfasserin |4 aut | |
| 700 | 1 | |a Altobelli, Giovanna Giuseppina |e verfasserin |4 aut | |
| 700 | 1 | |a Rinaldi, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Chiuso, Francesco |e verfasserin |4 aut | |
| 700 | 1 | |a Feliciello, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Dal Piaz, Fabrizio |e verfasserin |4 aut | |
| 700 | 1 | |a Campiglia, Pietro |e verfasserin |4 aut | |
| 700 | 1 | |a Ciccarelli, Michele |e verfasserin |4 aut | |
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| 700 | 1 | |a Iaccarino, Guido |e verfasserin |4 aut | |
| 700 | 1 | |a Sorriento, Daniela |e verfasserin |4 aut | |
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