1. NETs promote pathogenic cardiac fibrosis and participate in ventricular aneurysm formation after ischemia injury through the facilitation of perivascular fibrosis.
- Author
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He, Li, Liu, Ruiqi, Yue, Honghua, Zhu, Guonian, Fu, Li, Chen, Hongying, Guo, Yingqiang, and Qin, Chaoyi
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HEART fibrosis , *FIBROSIS , *CELLULAR signal transduction , *ANEURYSMS , *MYOCARDIAL infarction , *SINUS of valsalva , *NEUTROPHILS - Abstract
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. • Identifying that NETs participate in the fibrosis after MI and lead to the formation of ventricular aneurysm. • Identifying that Ventricular aneurysm formed after MI follows the pattern of perivascular fibrosis expansion where NETs exist and crosslinked with thrombosis. • Describing that NETs could induce the differentiation from cardiac fibroblast to myofibroblast and upregulate collagen synthesis. • Employing Dnase I administration as disrupt the DNA skeleton of NETs to abrogate NETs induced fibrotic upregulation both in vivo and vitro. • Providing an accessible and replicable method for neutrophils isolation and NETs acquirement from rats. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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