Oncotarget

Research Papers:

MiR-124 aggravates failing hearts by suppressing CD151-facilitated angiogenesis in heart

Yanru Zhao _, Mengwen Yan, Chen Chen, Wei Gong, Zhongwei Yin, Huaping Li, Jiahui Fan, Xin A. Zhang, Dao Wen Wang and Houjuan Zuo

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Oncotarget. 2018; 9:14382-14396. https://doi.org/10.18632/oncotarget.24205

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Abstract

Yanru Zhao1,*, Mengwen Yan1,2,*, Chen Chen1,*, Wei Gong1,3, Zhongwei Yin1, Huaping Li1, Jiahui Fan1, Xin A. Zhang4, Dao Wen Wang1 and Houjuan Zuo1

1Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China

2Department of Cardiology, China-Japan Friendship Hospital, Beijing, China

3Emergency and Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

4Stephenson Cancer Center and Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma, OK, USA

*These authors contributed equally to this work

Correspondence to:

Houjuan Zuo, email: zuohoujuan@126.com

Keywords: miRNA; angiogenesis; hypertrophy; heart failure; CD151

Received: October 26, 2017     Accepted: December 05, 2017     Epub: January 12, 2018     Published: March 06, 2018

ABSTRACT

Heart failure (HF) is the final common pathway of various cardiovascular diseases. Although it is well documented that reduction of cardiac angiogenesis contributes to the progression from adaptive cardiac hypertrophy to HF, the molecular mechanisms remain unknown. In the present study, we found that cardiac expression of miR-124 was increased in patients and mice with HF. Recombinant adeno-associated virus (rAAV)-mediated miR-124 over-expression aggravated angiotensin II (Ang II) infusion-induced cardiac dysfunction and abnormal cardiac angiogenesis in mice. In vitro, transfection of miR-124 mimics significantly promoted apoptosis and reduced viability, migration, tube formation, and nitric oxide release in endothelial cells. In addition, CD151 was identified as a direct target of miR-124. Endothelial cell injury caused by CD151 silencing was mimicked by miR-124 over-expression. Re-expression of CD151 attenuated miR-124-mediated suppression of cardiac angiogenesis and cardiac dysfunction in Ang II-treated mice. Our observations suggest that miR-124 is an important negative regulator of cardiac angiogenesis and cardiac function, likely by suppressing the expression of CD151 in heart cells. Modulation of miR-124 levels may provide new strategies and targets for HF therapy.


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