Myeloid differentiation 2 deficiency attenuates AngII-induced arterial vascular oxidative stress, inflammation, and remodeling.
Myeloid differentiation 2 deficiency attenuates AngII-induced arterial vascular oxidative stress, inflammation, and remodeling.
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DOI：
10.18632/aging.202402
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发表时间：
2021-01-20
期刊：
影响因子：
--
通讯作者：
Wu G
中科院分区：
文献类型：
--
作者：
Huang S;You S;Qian J;Dai C;Shen S;Wang J;Huang W;Liang G;Wu G
血管重塑是心血管治疗的相关靶点。血管平滑肌细胞（VSMC）功能障碍在血管重构中起着关键作用。髓样分化2（MD2）是Toll样受体4（TLR4）的辅因子，通过激活慢性炎症参与动脉粥样硬化的进展和心脏重塑。在这项研究中，我们探讨了MD2在血管重塑中的作用，使用血管紧张素II诱导的小鼠模型和培养的人主动脉VSMCs。MD2缺陷抑制Ang II诱导的血管纤维化和VSMCs的表型转换，而不影响小鼠的血压。在机制上，MD2缺陷阻止了小鼠和培养的VSMCs中Ang II诱导的炎性细胞因子和氧化应激的表达。此外，MD2缺陷逆转了Ang II激活的MAPK信号传导和Ang II下调SIRT1表达。总之，MD2在Ang II诱导的血管氧化应激、炎症和重塑中起重要作用，表明MD2是治疗血管重塑相关心血管疾病的潜在治疗靶点。
Vascular remodeling is a pertinent target for cardiovascular therapy. Vascular smooth muscle cell (VSMC) dysfunction plays a key role in vascular remodeling. Myeloid differentiation 2 (MD2), a cofactor of toll-like receptor 4 (TLR4), is involved in atherosclerotic progress and cardiac remodeling via activation of chronic inflammation. In this study, we explored the role of MD2 in vascular remodeling using an Ang II-induced mouse model and cultured human aortic VSMCs. MD2 deficiency suppressed Ang II-induced vascular fibrosis and phenotypic switching of VSMCs without affecting blood pressure in mice. Mechanistically, MD2 deficiency prevented Ang II-induced expression of inflammatory cytokines and oxidative stress in mice and cultured VSMCs. Furthermore, MD2 deficiency reversed Ang II-activated MAPK signaling and Ang II-downregulated SIRT1 expression. Taken together, MD2 plays a significant role in Ang II-induced vascular oxidative stress, inflammation, and remodeling, indicating that MD2 is a potential therapeutic target for the treatment of vascular remodeling-related cardiovascular diseases.
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DOI：
10.1161/hypertensionaha.115.05344
发表时间：
2015-06
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Takayanagi T;Kawai T;Forrester SJ;Obama T;Tsuji T;Fukuda Y;Elliott KJ;Tilley DG;Davisson RL;Park JY;Eguchi S
通讯作者：
Eguchi S
影响因子：
8
作者：
Becatti, Matteo;Taddei, Niccolo;Fiorillo, Claudia
通讯作者：
Fiorillo, Claudia
影响因子：
20.3
作者：
Shi, Guanfang;Field, David J.;Morrell, Craig N.
通讯作者：
Morrell, Craig N.
DOI：
10.1161/hypertensionaha.116.08278
发表时间：
2017-01
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Forrester SJ;Elliott KJ;Kawai T;Obama T;Boyer MJ;Preston KJ;Yan Z;Eguchi S;Rizzo V
通讯作者：
Rizzo V
抑制 Toll 样受体 2 通过减轻巨噬细胞介导的炎症来减少心脏纤维化
影响因子：
10.8
作者：
Wang, Lei;Li, Yu-Lin;Li, Hui-Hua
通讯作者：
Li, Hui-Hua