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

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 r...

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Detalles Bibliográficos
Autores principales: Fan, Jiahui, Li, Huaping, Nie, Xiang, Yin, Zhongwei, Zhao, Yanru, Zhang, Xudong, Yuan, Shuai, Li, Yuying, Chen, Chen, Wang, Dao Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188485/
https://www.ncbi.nlm.nih.gov/pubmed/30243022
http://dx.doi.org/10.18632/aging.101562
Descripción
Sumario: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.