Toll-like receptor 2 signaling deficiency in cardiac cells ameliorates Ang II-induced cardiac inflammation and remodeling.
Toll-like receptor 2 signaling deficiency in cardiac cells ameliorates Ang II-induced cardiac inflammation and remodeling.
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DOI：
10.1016/j.trsl.2021.02.011
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发表时间：
2021-02
期刊：
影响因子：
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通讯作者：
S. Ye;Ke Lin;Gaojun Wu;Ming-jiang Xu;P. Shan;Weijian Huang;Yi Wang;G. Liang
中科院分区：
文献类型：
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作者：
S. Ye;Ke Lin;Gaojun Wu;Ming-jiang Xu;P. Shan;Weijian Huang;Yi Wang;G. Liang
先天免疫系统的激活是血管紧张素II（Ang II）诱导的心脏重塑过程中炎症的重要步骤。本研究旨在探讨Toll样受体2（TLR 2）在血管紧张素II（Ang II）诱导的心脏重构中的作用。我们利用TLR 2基因敲除小鼠、骨髓移植模型和H9 C2细胞研究了TLR 2缺陷对Ang II诱导的心脏重构的影响。尽管TLR 2缺乏对体重变化、心脏Ang II含量和血压没有影响，但它显著改善了心脏肥大、纤维化和炎症，并改善了心功能。进一步的骨髓移植研究表明，心肌细胞中TLR 2的缺乏而不是骨髓来源的细胞阻止了Ang II诱导的心脏重塑和心脏功能障碍。其潜在机制可能涉及增加TLR 2-MyD 88相互作用。在Ang II处理的H9 C2细胞中的进一步体外研究显示，通过siRNA敲低TLR 2显著降低Ang II诱导的细胞肥大、纤维化和炎症。此外，Ang II以TLR 4非依赖性方式显著增加H9 C2细胞中TLR 2-MyD 88的相互作用。心肌细胞中TLR 2缺陷通过减少TLR 2-MyD 88复合物的形成来防止Ang II诱导的心脏重塑、炎症和功能障碍。抑制TLR 2通路可能是高血压性心力衰竭的治疗策略之一。
Activation of the innate immune system represents a vital step in inflammation during cardiac remodeling induced by the angiotensin II (Ang II). This study aimed to explore the role of Toll-like receptors 2 (TLR2) in Ang II-induced cardiac remodeling. We investigated the effect of TLR2 deficiency on Ang II-induced cardiac remodeling by utilizing TLR2 knockout mice, bone marrow transplantation models, and H9C2 cells. Though TLR2 deficiency had no effect on body weight change, cardiac Ang II content and blood pressure, it significantly ameliorated cardiac hypertrophy, fibrosis and inflammation, as well as improved heart function. Further bone marrow transplantation studies showed that TLR2-deficiency in cardiac cells but not bone marrow-derived cells prevented Ang II-induced cardiac remodeling and cardiac dysfunction. The underlying mechanism may involve increased TLR2-MyD88 interaction. Further in vitro studies in Ang II-treated H9C2 cells showed that TLR2 knockdown by siRNA significantly decreased Ang II-induced cell hypertrophy, fibrosis and inflammation. Moreover, Ang II significantly increased TLR2-MyD88 interaction in H9C2 cells in a TLR4-independent manner. TLR2 deficiency in cardiac cells prevents Ang II-induced cardiac remodeling, inflammation and dysfunction through reducing the formation of TLR2-MyD88 complexes. Inhibition of TLR2 pathway may be a therapeutic strategy of hypertensive heart failure.