Research Paper Volume 10, Issue 9 pp 2459—2479
MiR-665 aggravates heart failure via suppressing CD34-mediated coronary microvessel angiogenesis
- 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.101562How to Cite
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.