TY - JOUR
TI - 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
AU - Tsoporis, J.N.
AU - Fazio, A.
AU - Rizos, I.K.
AU - Izhar, S.
AU - Proteau, G.
AU - Salpeas, V.
AU - Rigopoulos, A.
AU - Sakadakis, E.
AU - Toumpoulis, I.K.
AU - Parker, T.G.
JO - Journal of Molecular and Cellular Cardiology
PY - 2018
VL - 121
TODO - null
SP - 25-32
PB - INSTAP Academic Press
SN - 0022-2828, 1095-8584
TODO - 10.1016/j.yjmcc.2018.06.005
TODO - 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
TODO - 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
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