脂多糖
炎症
炎症体
医学
心肌病
下调和上调
基因敲除
自噬
心脏功能不全
内科学
免疫学
癌症研究
药理学
化学
心力衰竭
细胞凋亡
生物化学
基因
作者
Jun Li,Ting Wan,Cheng Liu,Huadong Liu,Dong Ke,Luocheng Li
标识
DOI:10.1016/j.intimp.2023.110701
摘要
Angiopoietin-like protein 2 (ANGPTL2) was implicated in various cardiovascular diseases; however, its role in lipopolysaccharide (LPS)-related septic cardiomyopathy remains unclear. Herein, mice were exposed to LPS to generate septic cardiomyopathy, and adeno-associated viral vector was employed to overexpress ANGPTL2 in the myocardium. Besides, mice were treated with adenoviral vector to knock down ANGPTL2 in hearts. ANGPTL2 expressions in hearts and cardiomyocytes were upregulated by LPS challenge. ANGPTL2 overexpression aggravated, while ANGPTL2 silence ameliorated LPS-associated cardiac impairment and inflammation. Mechanically, we found that ANGPTL2 activated NLRP3 inflammasome via suppressing DUSP1 signaling, and NLRP3 knockdown abrogated the detrimental role of ANGPTL2 in aggravating LPS-induced cardiac inflammation. Furthermore, DUSP1 overexpression significantly inhibited ANGPTL2-mediated NLRP3 activation, and subsequently improved LPS-related cardiac dysfunction. In summary, ANGPTL2 exacerbated septic cardiomyopathy via activating NLRP3-mediated inflammation in a DUSP1-dependent manner, and our study uncovered a promising therapeutic target in preventing septic cardiomyopathy.
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