He Li, Liu Ruiqi, Yue Honghua, Zhu Guonian, Fu Li, Chen Hongying, Guo Yingqiang, Qin Chaoyi
Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China.
Department of Burn and Plastic Surgery, West China Hospital, Sichuan University, Chengdu, China.
Biochem Biophys Res Commun. 2021 Oct 29;583:154-161. doi: 10.1016/j.bbrc.2021.10.068.
Fibrosis has been widely investigated in acute phase of myocardial infarction (MI). However, the mechanism of sustained fibrosis after MI hasn't been elucidated, which eventually gives rise to ventricular aneurysm (VA) formation chronic while lethal. Neutrophil as vital cell facilitating the fibrotic repair after acute MI may not project its effect to chronic phase unless neutrophil extracellular traps (NETs) were secreted and accumulating. The aim of this study was to investigate whether NETs contribute to the sustained fibrosis and VA formation after MI. We identified NETs in ventricular aneurysm of patients. Accordingly, NETs increased in peripheral blood of VA patients. Moreover, in rat VA NETs were also identified. Stimulated by NETs, the migration of fibroblast was enhanced and the differentiation of cardiac myofibroblast was initiated. Smad, MAPK and RhoA signaling pathways were activated by NETs incubation. And additional deposition with DNase I to disrupt NETs and abrogated NETs induced fibrosis both in vivo and vitro. These results collectively demonstrate a novel profibrotic role for NETs in chronic cardiac fibrosis and VA formation.
纤维化在心肌梗死（MI）急性期已得到广泛研究。然而，MI后持续性纤维化的机制尚未阐明，最终会导致慢性致命性室壁瘤（VA）形成。中性粒细胞作为急性MI后促进纤维化修复的重要细胞，除非分泌并积累中性粒细胞胞外陷阱（NETs），否则可能无法将其作用延伸至慢性期。本研究旨在探讨NETs是否促成MI后持续性纤维化和VA形成。我们在患者的室壁瘤中鉴定出了NETs。相应地，VA患者外周血中的NETs增加。此外，在大鼠VA中也鉴定出了NETs。受NETs刺激，成纤维细胞的迁移增强，心肌成纤维细胞的分化启动。NETs孵育激活了Smad、MAPK和RhoA信号通路。用脱氧核糖核酸酶I额外沉积以破坏NETs，可在体内和体外消除NETs诱导的纤维化。这些结果共同证明了NETs在慢性心脏纤维化和VA形成中具有新的促纤维化作用。
