Vericiguat improves cardiac remodelling and function in rats with doxorubicin‐induced cardiomyopathy
Abstract Purpose Vericiguat, a soluble guanylate cyclase (sGC) stimulator, has been demonstrated effective in improving prognosis of patients with heart failure with reduced ejection fraction. However, there are limited data concerning the effect of vericiguat in patients with doxorubicin (DOX)‐indu...
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| Language: | English |
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Wiley
2025-06-01
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| Series: | ESC Heart Failure |
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| Online Access: | https://doi.org/10.1002/ehf2.15186 |
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| author | Wen Chen Ying Wu Wei Li Meiyan Song Kaizu Xu Meifang Wu Liming Lin |
| author_facet | Wen Chen Ying Wu Wei Li Meiyan Song Kaizu Xu Meifang Wu Liming Lin |
| author_sort | Wen Chen |
| collection | DOAJ |
| description | Abstract Purpose Vericiguat, a soluble guanylate cyclase (sGC) stimulator, has been demonstrated effective in improving prognosis of patients with heart failure with reduced ejection fraction. However, there are limited data concerning the effect of vericiguat in patients with doxorubicin (DOX)‐induced cardiomyopathy (DIC). In this study, we investigated the effects of vericiguat on cardiac structure and function in rats with DIC as well as their potential mechanisms of action. Methods DIC rats were established by intraperitoneal injection of DOX (1 mg/kg) twice a week for 6 weeks, followed by intragastric administration of vericiguat 1 mg/kg/day or an equal volume of normal saline for 8 weeks. Cardiac histology and function, circulating levels of amino‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), nitric oxide (NO), and oxidative indices, as well as myocardial cyclic guanosine monophosphate (cGMP)‐protein kinase G (PKG) signalling, oxidative and apoptosis‐associated protein were measured. Results Compared with the control group, rats treated with DOX exhibited significantly increased heart size, reduced systolic function and elevated plasma levels of NT‐proBNP. Histological findings revealed myocardial cell atrophy, fibrosis and apoptosis. Vericiguat treatment effectively reversed DOX‐induced cardiac remodelling and improved systolic function. Mechanistically, Vericiguat attenuated the inhibitory effects of DOX on the myocardial cGMP‐PKG axis and nuclear factor erythroid 2‐related factor 2 (Nrf2) protein, thereby alleviating oxidative stress and apoptosis. Conclusions Vericiguat improved cardiac remodelling and contractile function in rats with DIC through upregulation of cGMP‐PKG signalling and inhibition of oxidative stress and myocardial apoptosis. |
| format | Article |
| id | doaj-art-ccf0e5faa31846b9af78fc1701e0407b |
| institution | Kabale University |
| issn | 2055-5822 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj-art-ccf0e5faa31846b9af78fc1701e0407b2025-08-20T03:53:16ZengWileyESC Heart Failure2055-58222025-06-011231807181710.1002/ehf2.15186Vericiguat improves cardiac remodelling and function in rats with doxorubicin‐induced cardiomyopathyWen Chen0Ying Wu1Wei Li2Meiyan Song3Kaizu Xu4Meifang Wu5Liming Lin6School of Clinical Medicine, Fujian Medical University, Department of Cardiology Affiliated Hospital of Putian University Putian ChinaSchool of Clinical Medicine, Fujian Medical University, Department of Cardiology Affiliated Hospital of Putian University Putian ChinaSchool of Clinical Medicine, Fujian Medical University, Department of Cardiology Affiliated Hospital of Putian University Putian ChinaSchool of Clinical Medicine, Fujian Medical University, Department of Cardiology Affiliated Hospital of Putian University Putian ChinaSchool of Clinical Medicine, Fujian Medical University, Department of Cardiology Affiliated Hospital of Putian University Putian ChinaSchool of Clinical Medicine, Fujian Medical University, Department of Cardiology Affiliated Hospital of Putian University Putian ChinaSchool of Clinical Medicine, Fujian Medical University, Department of Cardiology Affiliated Hospital of Putian University Putian ChinaAbstract Purpose Vericiguat, a soluble guanylate cyclase (sGC) stimulator, has been demonstrated effective in improving prognosis of patients with heart failure with reduced ejection fraction. However, there are limited data concerning the effect of vericiguat in patients with doxorubicin (DOX)‐induced cardiomyopathy (DIC). In this study, we investigated the effects of vericiguat on cardiac structure and function in rats with DIC as well as their potential mechanisms of action. Methods DIC rats were established by intraperitoneal injection of DOX (1 mg/kg) twice a week for 6 weeks, followed by intragastric administration of vericiguat 1 mg/kg/day or an equal volume of normal saline for 8 weeks. Cardiac histology and function, circulating levels of amino‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), nitric oxide (NO), and oxidative indices, as well as myocardial cyclic guanosine monophosphate (cGMP)‐protein kinase G (PKG) signalling, oxidative and apoptosis‐associated protein were measured. Results Compared with the control group, rats treated with DOX exhibited significantly increased heart size, reduced systolic function and elevated plasma levels of NT‐proBNP. Histological findings revealed myocardial cell atrophy, fibrosis and apoptosis. Vericiguat treatment effectively reversed DOX‐induced cardiac remodelling and improved systolic function. Mechanistically, Vericiguat attenuated the inhibitory effects of DOX on the myocardial cGMP‐PKG axis and nuclear factor erythroid 2‐related factor 2 (Nrf2) protein, thereby alleviating oxidative stress and apoptosis. Conclusions Vericiguat improved cardiac remodelling and contractile function in rats with DIC through upregulation of cGMP‐PKG signalling and inhibition of oxidative stress and myocardial apoptosis.https://doi.org/10.1002/ehf2.15186apoptosisdoxorubicin‐induced cardiomyopathyoxidative stresssoluble guanylate cyclasevericiguat |
| spellingShingle | Wen Chen Ying Wu Wei Li Meiyan Song Kaizu Xu Meifang Wu Liming Lin Vericiguat improves cardiac remodelling and function in rats with doxorubicin‐induced cardiomyopathy ESC Heart Failure apoptosis doxorubicin‐induced cardiomyopathy oxidative stress soluble guanylate cyclase vericiguat |
| title | Vericiguat improves cardiac remodelling and function in rats with doxorubicin‐induced cardiomyopathy |
| title_full | Vericiguat improves cardiac remodelling and function in rats with doxorubicin‐induced cardiomyopathy |
| title_fullStr | Vericiguat improves cardiac remodelling and function in rats with doxorubicin‐induced cardiomyopathy |
| title_full_unstemmed | Vericiguat improves cardiac remodelling and function in rats with doxorubicin‐induced cardiomyopathy |
| title_short | Vericiguat improves cardiac remodelling and function in rats with doxorubicin‐induced cardiomyopathy |
| title_sort | vericiguat improves cardiac remodelling and function in rats with doxorubicin induced cardiomyopathy |
| topic | apoptosis doxorubicin‐induced cardiomyopathy oxidative stress soluble guanylate cyclase vericiguat |
| url | https://doi.org/10.1002/ehf2.15186 |
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