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Updated: Mar 26, 2026
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
miR-320a mediates doxorubicin-induced cardiotoxicity by targeting VEGF signal pathway
Zhongwei Yin1, Yanru Zhao1, Huaping Li1
1Division of Cardiology, Departments of Internal Medicine and The Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Background:
Vascular homeostasis abnormalities may involve in doxorubicin induced cardiotoxicity.
Methods:
Enhanced cardiac miR-320a expression, reduced cardiac microvessel density and impaired cardiac function were observed in mice treated by anthracycline doxorubicin. To further explore the role of miR-320a in doxorubicin induced cardiotoxicity, microRNA mimics/inhibitor in vitro and rAAV administration in vivo were employed in mice.
Results:
Knockdown of miR-320a not only resulted in enhanced proliferation and inhibited apoptosis in cultured endothelial cells, but also attenuated cardiac abnormalities induced by doxorubicin. On the contrary, overexpression of miR-320a enhanced apoptosis in vitro, and aggravated vessel abnormalities in heart and subsequent cardiac dysfunction in mice. Furthermore, Western blot assays showed that VEGF-A was a potential target of miR-320a, which was verified by anti-Ago2 co-immunoprecipitation. Moreover, as same as miR-320a, siRNA against VEGF-A reinforced doxorubicin induced endothelial cells injury. Finally, the negative effects of miR-320a on vascular homeostasis and cardiac function were alleviated by VEGF-A re-expression in doxorubicin treated mice.
Conclusion:
Our observations demonstrate that miR-320a play important roles in doxorubicin induced cardiotoxicity via vessel homeostasis in heart and thus, inhibition of miR-320a may be applied to the treatment of cardiac dysfunction induced by anthracycline.
Insights
Inhibiting miR-320a protects against doxorubicin cardiotoxicity by improving vascular homeostasis. This microRNA (miRNA) targets VEGF-A, offering a potential therapeutic strategy for anthracycline-induced heart dysfunction.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Drug-Induced Toxicity
Background:
- Doxorubicin, an anthracycline chemotherapy, can cause cardiotoxicity.
- Abnormalities in vascular homeostasis are implicated in doxorubicin-induced cardiotoxicity.
Purpose of the Study:
- To investigate the role of microRNA-320a (miR-320a) in doxorubicin-induced cardiotoxicity.
- To explore miR-320a's impact on vascular homeostasis and cardiac function.
Main Methods:
- Utilized microRNA mimics/inhibitors in vitro and adeno-associated virus (AAV) delivery in vivo in mice.
- Assessed endothelial cell proliferation and apoptosis, cardiac microvessel density, and cardiac function.
- Investigated the interaction between miR-320a and Vascular Endothelial Growth Factor-A (VEGF-A) using Western blot and co-immunoprecipitation.
Main Results:
- Doxorubicin treatment increased cardiac miR-320a expression, reduced microvessel density, and impaired cardiac function.
- Knockdown of miR-320a attenuated doxorubicin-induced cardiac abnormalities and promoted endothelial cell proliferation.
- Overexpression of miR-320a exacerbated cardiac dysfunction and vascular abnormalities, with VEGF-A identified as a direct target.
Conclusions:
- miR-320a plays a critical role in doxorubicin-induced cardiotoxicity through its regulation of vascular homeostasis.
- Inhibition of miR-320a presents a potential therapeutic approach for treating anthracycline-induced cardiac dysfunction.
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