Research Paper Volume 10, Issue 9 pp 2459—2479

MiR-665 aggravates heart failure via suppressing CD34-mediated coronary microvessel angiogenesis

Jiahui Fan 1, 2, , Huaping Li 1, 2, , Xiang Nie 1, 2, , Zhongwei Yin 1, 2, , Yanru Zhao 1, 2, , Xudong Zhang 1, 2, , Shuai Yuan 1, 2, , Yuying Li 1, 2, , Chen Chen 1, 2, , Dao Wen Wang 1, 2, ,

  • 1 Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
  • 2 Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China

received: August 7, 2018 ; accepted: September 13, 2018 ; published: September 21, 2018 ;

https://doi.org/10.18632/aging.101562
How to Cite

Copyright: Fan et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Heart failure (HF) is a major public health problem worldwide. The development of HF was related to coronary microvessel dysfunction. Whether miRNAs participate in HF by regulating coronary microvessel function remain unclear.

Methods: The potential targets of miR-665 were predicted by rnahybrid software, then verified through anti-Ago2 co-immunoprecipitation, Western blotting and luciferase reporter assays. rAAV9 system was used to manipulate the expression of miR-665 in vivo.

Results: Significant increase of miR-665 was observed in endothelial cells of human heart with heart failure. In vitro over-expression of miR-665 in endothelial cells resulted in decreased proliferation but enhanced apoptosis. rAAV-mediated delivery of miR-665 reduced coronary microvessel angiogenesis and cardiac microvessel density, then further impaired cardiac function in vivo. Furthermore, CD34 was confirmed as one of the miR-665 targets. Consistently, re-expression of CD34 attenuated miR-665-mediated damage effects in vitro and in vivo. We also found that Sp1 regulated miR-665 expression in endothelial cells.

Conclusion: Our findings demonstrated that miR-665 played an important role in heart failure via damaging coronary microvessel angiogenesis, and suggested that miRNA-based therapeutics may protect against coronary microvessel dysfunction and heart failure.

Abbreviations

HF: heart failure; CHF: chronic heart failure; miRNA: microRNAs; HSCs: hematopoietic stem cells; CD34: CD34 molecule; IGF1: insulin like growth factor 1; VEGFA: vascular endothelial growth factor A; AKT3: AKT serine/threonine kinase 3.