NETs promote pathogenic cardiac fibrosis and participate in ventricular aneurysm formation after ischemia injury through the facilitation of perivascular fibrosis

Li He; Ruiqi Liu; Honghua Yue; Guonian Zhu; Li Fu; Hongying Chen; Yingqiang Guo; Chaoyi Qin

doi:10.1016/j.bbrc.2021.10.068

NETs promote pathogenic cardiac fibrosis and participate in ventricular aneurysm formation after ischemia injury through the facilitation of perivascular fibrosis

Biochem Biophys Res Commun. 2021 Oct 29:583:154-161. doi: 10.1016/j.bbrc.2021.10.068. Online ahead of print.

Authors

Li He¹, Ruiqi Liu², Honghua Yue¹, Guonian Zhu³, Li Fu⁴, Hongying Chen⁴, Yingqiang Guo⁵, Chaoyi Qin⁶

Affiliations

¹ Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China.
² Department of Burn and Plastic Surgery, West China Hospital, Sichuan University, Chengdu, China.
³ Institute of Respiratory Health, West China Hospital, Sichuan University, Chengdu, China.
⁴ Research Core Facility of West China Hospital, Sichuan University, Chengdu, China.
⁵ Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China. Electronic address: guoyq@hotmail.com.
⁶ Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China. Electronic address: qinchaoyi@wchscu.cn.

PMID: 34735877
DOI: 10.1016/j.bbrc.2021.10.068

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.

Keywords: Cardiac fibrosis; Myocardial infarction; NETs; Ventricular aneurysm.