Sacubitril/Valsartan Alleviates Experimental Autoimmune Myocarditis by Inhibiting Th17 Cell Differentiation Independently of the NLRP3 Inflammasome Pathway.
Sacubitril/Valsartan Alleviates Experimental Autoimmune Myocarditis by Inhibiting Th17 Cell Differentiation Independently of the NLRP3 Inflammasome Pathway.
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Sacubitril/Valsartan 通过独立于 NLRP3 炎症小体途径抑制 Th17 细胞分化来减轻实验性自身免疫性心肌炎
DOI：
10.3389/fphar.2021.727838
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发表时间：
2021
影响因子：
5.6
通讯作者：
Yu M
中科院分区：
文献类型：
--
作者：
Liang W;Xie BK;Ding PW;Wang M;Yuan J;Cheng X;Liao YH;Yu M
沙库巴曲/缬沙坦（Sacubitril/valsartan，Sac/瓦尔）是最近批准的一种常用于治疗心力衰竭的药物。一些研究表明Sac/瓦尔还调节炎症因子的分泌。然而，这种药物调节炎症免疫反应的效果和机制尚不清楚。本研究通过注射α-肌球蛋白重链肽建立了实验性自身免疫性心肌炎（EAM）小鼠模型。通过心脏组织的组织学染色、心肌肌钙蛋白T和炎性标志物（IL-6和hsCRP）的测量来评价口服Sac/瓦尔对EAM的影响。还测定了Sac/瓦尔对NLRP 3炎性体活化和Th 1/Th 17细胞分化的影响。为进一步探讨其信号通路，检测心肌可溶性鸟苷酸环化酶（sGC）和NF-κB p65的表达。结果表明，Sac/瓦尔下调了炎症反应，减轻了EAM的严重程度，但不影响NLRP 3炎性小体的激活。Sac/瓦尔处理抑制Th 17细胞的分化，这可能与sGC/NF-κB p65信号通路有关。这些发现表明Sac/瓦尔用于治疗心肌炎的潜在用途。
Sacubitril/valsartan (Sac/Val) is a recently approved drug that is commonly used for treatment of heart failure. Several studies indicated that Sac/Val also regulated the secretion of inflammatory factors. However, the effect and mechanism of this drug modulation of inflammatory immune responses are uncertain. In this study, an experimental autoimmune myocarditis (EAM) mouse model was established by injection of α-myosin-heavy chain peptides. The effect of oral Sac/Val on EAM was evaluated by histological staining of heart tissues, measurements of cardiac troponin T and inflammatory markers (IL-6 and hsCRP). The effects of Sac/Val on NLRP3 inflammasome activation and Th1/Th17 cell differentiation were also determined. To further explore the signaling pathways, the expressions of cardiac soluble guanylyl cyclase (sGC) and NF-κB p65 were investigated. The results showed that Sac/Val downregulated the inflammatory response and attenuated the severity of EAM, but did not influence NLRP3 inflammasomes activation. Moreover, Sac/Val treatment inhibited cardiac Th17 cell differentiation, and this might be associated with sGC/NF-κB p65 signaling pathway. These findings indicate the potential use of Sac/Val for treatment of myocarditis.
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影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
37.8
作者：
Eriksson, U;Kurrer, MO;Kopf, M
通讯作者：
Kopf, M
影响因子：
37.8
作者：
Cruz-Adalia, Aranzazu;Jesus Jimenez-Borreguero, Luis;Martin, Pilar
通讯作者：
Martin, Pilar
影响因子：
24
作者：
Kindermann, Ingrid;Barth, Christine;Boehm, Michael
通讯作者：
Boehm, Michael
DOI：
10.1056/nejmra0800028
发表时间：
2009-04-09
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cooper LT Jr
通讯作者：
Cooper LT Jr