Dihydromyricetin Attenuates TNF-α-Induced Endothelial Dysfunction through miR-21-Mediated DDAH1/ADMA/NO Signal Pathway.
Dihydromyricetin Attenuates TNF-α-Induced Endothelial Dysfunction through miR-21-Mediated DDAH1/ADMA/NO Signal Pathway.
复制标题
二氢杨梅素通过 miR-21 介导的 DDAH1/ADMA/NO 信号通路减轻 TNF-α 诱导的内皮功能障碍
DOI：
10.1155/2018/1047810
复制
发表时间：
2018
影响因子：
--
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Yang D;Tan S;Yang Z;Jiang P;Qin C;Yuan Q;Dang R;Yao X;Qu J;Lu Q;Xu P;Zhang B;Xiang D;Chen L
大量研究表明，二氢杨梅素(DMY)是一种从中草药显齿蛇葡萄中提取的化合物，可通过改善内皮功能障碍来延缓动脉粥样硬化的进程。然而，其潜在的机制仍然知之甚少。因此，本研究的目的是探讨DMY减轻肿瘤坏死因子-α-α诱导的内皮功能障碍的可能机制。作为对肿瘤坏死因子-α的响应，人脐静脉内皮细胞微RNA-21(miR-21)的表达显著增加，这与内皮功能障碍一致，表现为血管形成和迁移减少，内皮型一氧化氮合酶(ENOS)磷酸化，二甲基精氨酸二甲氨基水解酶1(DDAH1)的表达和代谢活性，一氧化氮(NO)浓度和不对称二甲基精氨酸水平增加。相反，DMY或阻断miR-21的表达可通过下调miR-21的表达来改善肿瘤坏死因子-α处理的HUVEC的内皮功能障碍，而这些作用被miR-21的过度表达所消除。此外，使用非特异性一氧化氮合酶抑制剂L-NAME，也取消了DMY对内皮细胞功能障碍的减轻作用。综上所述，这些结果表明miR-21介导的DDAH1/ADMA/NO信号通路在肿瘤坏死因子-α诱导的内皮功能障碍中起重要作用，DMY以miR-21依赖的方式减轻肿瘤坏死因子-α诱导的内皮功能障碍。
Accumulating studies demonstrate that dihydromyricetin (DMY), a compound extracted from Chinese traditional herb, Ampelopsis grossedentata, attenuates atherosclerotic process by improvement of endothelial dysfunction. However, the underlying mechanism remains poorly understood. Thus, the aim of this study is to investigate the potential mechanism behind the attenuating effects of DMY on tumor necrosis factor alpha- (TNF-α-) induced endothelial dysfunction. In response to TNF-α, microRNA-21 (miR-21) expression was significantly increased in human umbilical vein endothelial cells (HUVECs), in line with impaired endothelial dysfunction as evidenced by decreased tube formation and migration, endothelial nitric oxide synthase (eNOS) (ser1177) phosphorylation, dimethylarginine dimethylaminohydrolases 1 (DDAH1) expression and metabolic activity, and nitric oxide (NO) concentration as well as increased asymmetric dimethylarginine (ADMA) levels. In contrast, DMY or blockade of miR-21 expression ameliorated endothelial dysfunction in HUVECs treated with TNF-α through downregulation of miR-21 expression, whereas these effects were abolished by overexpression of miR-21. In addition, using a nonspecific NOS inhibitor, L-NAME, also abrogated the attenuating effects of DMY on endothelial dysfunction. Taken together, these data demonstrated that miR-21-mediated DDAH1/ADMA/NO signal pathway plays an important role in TNF-α-induced endothelial dysfunction, and DMY attenuated endothelial dysfunction induced by TNF-α in a miR-21-dependent manner.
登录
查看更多内容
影响因子：
5.8
作者：
Sun X;Belkin N;Feinberg MW
通讯作者：
Feinberg MW
三七皂苷 R1 减轻 ApoE 缺陷小鼠模型中的动脉粥样硬化病变
影响因子：
3.7
作者：
Jia C;Xiong M;Wang P;Cui J;Du X;Yang Q;Wang W;Chen Y;Zhang T
通讯作者：
Zhang T
影响因子：
8.2
作者：
Liu, Ya-rong;Chen, Jun-jun;Dai, Min
通讯作者：
Dai, Min
影响因子：
20.1
作者：
Wang, Dan;Gill, Pritmohinder S.;Wilcox, Christopher S.
通讯作者：
Wilcox, Christopher S.
4-HNE 增加培养的 HUVEC 细胞内 ADMA 水平：miR-21 依赖性机制的证据
影响因子：
3.7
作者：
Chen L;Zhou JP;Kuang DB;Tang J;Li YJ;Chen XP
通讯作者：
Chen XP