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miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1: miR-205-5p inhibits pulmonary microvascular endothelial dysfunction

Homocysteine (Hcy) is a risk factor for multiple chronic diseases, and vascular endothelial cell injury has been regarded as the initiating step for this process. miRNAs are involved in Hcy-induced endothelial dysfunction, while the underlying mechanism and roles of miRNAs in pulmonary endothelial d...

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Detalles Bibliográficos
Autores principales: Huang, Xiaobo, Li, Zhen, Zhang, Ling, Yang, Yali, Wang, Yanjia, Li, Sirui, Li, Guizhong, Feng, Huiping, Yang, Xiaoling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520487/
https://www.ncbi.nlm.nih.gov/pubmed/37491880
http://dx.doi.org/10.3724/abbs.2023127
Descripción
Sumario:Homocysteine (Hcy) is a risk factor for multiple chronic diseases, and vascular endothelial cell injury has been regarded as the initiating step for this process. miRNAs are involved in Hcy-induced endothelial dysfunction, while the underlying mechanism and roles of miRNAs in pulmonary endothelial dysfunction induced by homocysteine are unknown. Here, we find that miR-205-5p alleviates pulmonary endothelial dysfunction by targeting FOXO1 in CBS (+/‒) mice to protect against Hcy-induced pulmonary endothelial dysfunction. Mechanistically, we show that Hcy can lead to DNA hypermethylation of the miR-205-5p promoter due to the increased binding of DNMT1 to its promoter, which contributes to reduction of miR-205-5p expression. In summary, miR-205-5p promoter hypermethylation causes downregulation of miR-205-5p expression, resulting in a reduction in miR-205-5p binding to FOXO1 during homocysteine-induced pulmonary endothelial dysfunction. Our data indicate that miR-205-5p may be a potential therapeutic target against Hcy-induced pulmonary injury.