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长链非编码 RNA Sirt1-AS 通过上调 Sirt1 来减轻与衰老相关的深静脉血栓形成。

LncRNA Sirt1-AS upregulates Sirt1 to attenuate aging related deep venous thrombosis.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.

Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi, China.

出版信息

Aging (Albany NY). 2021 Feb 26;13(5):6918-6935. doi: 10.18632/aging.202550.

Abstract

Aging is associated with the increased incidence of deep venous thrombosis (DVT), resulting in significant morbidity and mortality in the elderly, but the underlying mechanism is elusive. Silent information regulator 1 (Sirt1) is linked to the senescence, inflammation, oxidative stress and platelet adhesion of endothelial cells. Here we showed that DVT was associated with the senescence of endothelium and lower expression of Sirt1. Furthermore, Sirt1 could inhibit endothelial senescence and reduce the occurrence of DVT. Interestingly, we found antisense long non-coding RNA (lncRNA Sirt1-AS) upregulated Sirt1, decreased the expression of senescence and DVT associated biomarkers in human vascular endothelial cells (HUVECs). In addition, lncRNA Sirt1-AS overexpression alleviated DVT through upregulating Sirt1 and thereby inducing Foxo3a degradation. In conclusion, our findings demonstrate that lncRNA Sirt1-AS may be a potential new biomarker for DVT.

摘要

衰老与深静脉血栓形成(DVT)的发生率增加有关,导致老年人发病率和死亡率显著增加,但潜在机制尚不清楚。沉默信息调节因子 1(Sirt1)与内皮细胞衰老、炎症、氧化应激和血小板黏附有关。本研究表明,DVT 与内皮细胞衰老和 Sirt1 表达降低有关。此外,Sirt1 可抑制内皮细胞衰老,减少 DVT 的发生。有趣的是,我们发现反义长链非编码 RNA(lncRNA Sirt1-AS)可上调 Sirt1,降低人血管内皮细胞(HUVECs)中与衰老和 DVT 相关的生物标志物的表达。此外,lncRNA Sirt1-AS 的过表达通过上调 Sirt1 从而诱导 Foxo3a 降解来减轻 DVT。总之,我们的研究结果表明,lncRNA Sirt1-AS 可能是 DVT 的一个潜在的新生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d19/7993686/92c1692a7313/aging-13-202550-g001.jpg

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