Abstract:
Background:Angiotensin II (Ang II) could promote the development of atrial fibrosis in atrial fibrillation (AF). Apelin can inhibit the occurrence of myocardial fibrosis. However, the effect of apelin on Ang II-induced atrial fibrosis and subsequent AF still remains unknown. Objective:In the present study, we examined the effect of apelin on the suppression of atrial fibrosis and subsequent AF, and investigated its underlying mechanisms. Methods:Sprague-Dawley rats were treated for 2 weeks with Ang II (1080 μg/kg/24 h) and apelin-13 (140 μg/kg/24 h) using implantable mini-pumps. The incidence of AF induced by atrial pacing was determined. Atrial electrophysiological mapping was recorded by a 32-electrode microelectrode array. Blood was collected to measure the levels of Ang II and apelin. Atrial tissue samples were preserved to assess the pathohistological changes, DDR2 and α-SMA co-staining were performed, and the protein expression of Smad2 phosphorylation was evaluated. Results:Apelin significantly inhibited Ang II-induced atrial fibrosis (HE:1.45 ± 0.11 vs 6.12 ± 0.16, P < 0.001; Masson:1.49 ± 0.25 vs 8.15 ± 0.23, P < 0.001; Picrosirius Red:1.98 ± 0.64 vs 9.59 ± 0.56, P < 0.001, respectively) and decreased the vulnerability of AF (inducibility of AF: z = -4.40, P < 0.001; total AF duration: z = -4.349, P < 0.001). Left atrial epicardial mapping studies demonstrated preservation of atrial conduction homogeneity by apelin. The protective effects of apelin from fibrotic remodeling were mediated by suppression of Smad2-dependent fibrosis. Conclusion:Apelin potently inhibited Ang II-induced atrial fibrosis and subsequent vulnerability to AF induction via suppression TGF-β/Smad2/α-SMA pathway. Our results indicated that apelin might be an effective up-stream therapy for atrial fibrosis and AF.
journal_name
Front Physioljournal_title
Frontiers in physiologyauthors
Lv W,Zhang L,Cheng X,Wang H,Qin W,Zhou X,Tang Bdoi
10.3389/fphys.2020.583570subject
Has Abstractpub_date
2020-11-19 00:00:00pages
583570issn
1664-042Xjournal_volume
11pub_type
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