Silica nanoparticles induce JNK-mediated inflammation and myocardial contractile dysfunction
Silica nanoparticles induce JNK-mediated inflammation and myocardial contractile dysfunction
复制标题
二氧化硅纳米粒子诱导 JNK 介导的炎症和心肌收缩功能障碍
DOI：
10.1016/j.jhazmat.2020.122206
复制
发表时间：
2020-06-05
影响因子：
13.6
通讯作者：
Sun, Zhiwei
中科院分区：
文献类型：
--
作者：
Feng, Lin;Ning, Ruihong;Sun, Zhiwei
Increasing environmental exposure to silica nanoparticles (SiNPs) and limited cardiotoxicity studies posed a challenge for the safety evaluation and management of these materials. This study aimed to explore the adverse effects and underlying mechanisms of subacute exposure to SiNPs on cardiac function in rats. Results from echocardiographic, ultrastructural and histopathological analysis found that SiNPs induced cardiac contractile dysfunction, accompanied by incomplete myocardial structures, disordered sarcomere segments, interstitial edema and myocyte apoptosis in heart. Levels of myocardial enzymes and inflammatory factors were markedly increased in both serum and heart tissue, accompanied by elevated levels of oxidative damage occurred in the hearts of SiNPs-treated rats. SiNPs significantly upregulated the expressions of inflammation and contraction-related proteins, including JNK, p-JNK, c-Jun, TF and PAR1. Lentivirus transfection of JNK shRNA showed the low-expression of JNK-facilitated F-actin and inhibited TF in the SiNPs-treated cardiomyocytes. Moreover, SiNPs activated the mRNA and protein levels of JNK/TF/PAR1 pathway, and these effects were significantly dampened after JNK knock down. Our results demonstrate that SiNPs trigger myocardial contractile dysfunction via JNK/TF/PAR1 signaling pathway.
