Increased right atrial appendage apoptosis is associated with differential regulation of candidate MicroRNAs 1 and 133A in patients who developed atrial fibrillation after cardiac surgery

Increased right atrial appendage apoptosis is associated with differential regulation of candidate MicroRNAs 1 and 133A in patients who developed atrial fibrillation after cardiac surgery

Atrial fibrillation (AF) following on-pump coronary artery bypass grafting (CABG) is a common condition associated with increased morbidity and mortality. We investigated the possibility that miRs may play a contributory role in postoperative AF and associated apoptosis. A total of 42 patients (31 m...

Full description

Saved in:
Bibliographic Details
Published in:Journal of molecular and cellular cardiology Vol. 121; pp. 25 - 32
Main Authors: Tsoporis, James N., Fazio, Anastasia, Rizos, Ioannis K., Izhar, Shehla, Proteau, Gerald, Salpeas, Vasileos, Rigopoulos, Angelos, Sakadakis, Eleftherios, Toumpoulis, Ioannis K., Parker, Thomas G.
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01-08-2018
Subjects:
Akt
Apoptosis
Atrial fibrillation
Hypoxia
microRNA
microRNA
Hypoxia
Akt
Atrial fibrillation
Apoptosis
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Atrial fibrillation (AF) following on-pump coronary artery bypass grafting (CABG) is a common condition associated with increased morbidity and mortality. We investigated the possibility that miRs may play a contributory role in postoperative AF and associated apoptosis. A total of 42 patients (31 males and 11 females, mean age 65.0 ± 1.3 years) with sinus rhythm and without a history of AF were prospectively enrolled. We examined the levels of the muscle-specific miRs 1 and 133A and markers of apoptosis including TUNEL staining, caspase-3 activation, Bcl2 and Bax mRNAs in right atrial appendage (RAA) biopsies and blood plasma taken before aortic cross-clamping and after reperfusion. After reperfusion, indices of apoptosis increased the RAA. There was no change in tissue or plasma miR −1 and -133A levels compared to pre CABG. However, in patients who postoperatively developed AF (n = 14, 7 males and 7 females), compared to patients that remained in SR (n = 28, 24 males and 4 females) post CABG, tissue miR-1 increased whereas miR-133A decreased and negatively correlated with RAA apoptosis. Mechanistically, overexpression of miR-133A inhibited hypoxia-induced rat neonatal cardiomyocyte apoptosis and phosphorylated pro-survival Akt, responses abolished by a miR-133A antisense inhibitor oligonucleotide or by pre-treatment with an Akt inhibitor. In postoperative AF, differential regulation of pro- and anti-apoptotic miRs-1 and -133A respectively in the RAA, may contribute to postoperative apoptosis. These results provide new insights into molecular mechanisms of postoperative AF with potential therapeutic implications. •Post-operative atrial fibrillation (POAF) induces right atrial appendage (RAA) apoptosis.•POAF, pro-apoptotic miR-1 is upregulated in the RAA.•POAF, anti-apoptotic miR-133A is downregulated in the RAA.•Plasma miRs -1 and -133A do not change POAF.•miR-133A inhibits hypoxic-induced cardiomyocyte apoptosis via Akt signaling.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0022-2828
1095-8584
DOI:10.1016/j.yjmcc.2018.06.005