MiR-320a Mediates Doxorubicin-induced Cardiotoxicity by Targeting VEGF Signal Pathway

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2016 Feb 4

PMID 26837315

Citations 48

Authors

Zhongwei Yin

Yanru Zhao

Huaping Li

Mengwen Yan

Ling Zhou

Chen Chen

Dao Wen Wang

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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