Τίτλος:
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
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2018 Elsevier Ltd
Συγγραφείς:
Tsoporis, J.N.
Fazio, A.
Rizos, I.K.
Izhar, S.
Proteau, G.
Salpeas, V.
Rigopoulos, A.
Sakadakis, E.
Toumpoulis, I.K.
Parker, T.G.
Περιοδικό:
Journal of Molecular and Cellular Cardiology
Εκδότης:
INSTAP Academic Press
Λέξεις-κλειδιά:
caspase 3; messenger RNA; microRNA; microRNA 1; microRNA 133a; protein Bax; protein bcl 2; protein kinase B; unclassified drug; microRNA; MIRN1 microRNA, human; MIRN133 microRNA, human, aged; animal cell; aortic clamping; apoptosis; Article; atrial fibrillation; bax gene; Bcl2 gene; blood sampling; clinical article; controlled study; coronary artery bypass graft; coronary artery disease; enzyme activation; enzyme phosphorylation; female; gene overexpression; heart atrium appendage; heart perfusion; human; human tissue; male; newborn; nonhuman; postoperative complication; priority journal; rat; regulatory mechanism; sinus rhythm; TUNEL assay; adverse event; apoptosis; atrial fibrillation; biopsy; blood; cell differentiation; coronary artery bypass graft; gene expression regulation; genetics; heart atrium; heart atrium appendage; heart surgery; metabolism; pathology, Aged; Apoptosis; Atrial Appendage; Atrial Fibrillation; Biopsy; Cardiac Surgical Procedures; Cell Differentiation; Coronary Artery Bypass; Female; Gene Expression Regulation; Heart Atria; Humans; Male; MicroRNAs
DOI:
10.1016/j.yjmcc.2018.06.005
