Authors
Chunxia Yao, Tina Veleva, Larry Scott Jr, Shuyi Cao, Luge Li, Gong Chen, Prince Jeyabal, Xiaolu Pan, Katherina M Alsina, Issam Abu-Taha, Shokoufeh Ghezelbash, Corey L Reynolds, Ying H Shen, Scott A LeMaire, Wilhelm Schmitz, Frank U Müller, Ali El-Armouche, N Tony Eissa, Christine Beeton, Stanley Nattel, Xander HT Wehrens, Dobromir Dobrev, Na Li
Publication date
2018/11/13
Journal
Circulation
Volume
138
Issue
20
Pages
2227-2242
Publisher
Lippincott Williams & Wilkins
Description
Background
Atrial fibrillation (AF) is frequently associated with enhanced inflammatory response. The NLRP3 (NACHT, LRR, and PYD domain containing protein 3) inflammasome mediates caspase-1 activation and interleukin-1β release in immune cells but is not known to play a role in cardiomyocytes (CMs). Here, we assessed the role of CM NLRP3 inflammasome in AF.
Methods
NLRP3 inflammasome activation was assessed by immunoblot in atrial whole-tissue lysates and CMs from patients with paroxysmal AF or long-standing persistent (chronic) AF. To determine whether CM-specific activation of NLPR3 is sufficient to promote AF, a CM-specific knockin mouse model expressing constitutively active NLRP3 (CM-KI) was established. In vivo electrophysiology was used to assess atrial arrhythmia vulnerability. To evaluate the mechanism of AF, electric activation pattern, Ca2+ spark frequency, atrial effective …
Scholar articles
C Yao, T Veleva, L Scott Jr, S Cao, L Li, G Chen… - Circulation, 2018