Abstract 17714: Differential Atrial Regulation of Candidate mir-1, mir-133a and mir-328 in Patients Following On-Pump Coronary Artery Bypass Grafting

Abstract

Atrial fibrillation (AF) following on-pump coronary artery bypass grafting (CABG) is a relatively common condition associated with increased morbidity, in-hospital length of stay and mortality. The possibility that microRNAs (miRs) may be involved in this process has not been fully investigated. Accordingly, we aimed to identify miRs that may play a contributory role in postoperative AF and associated apoptosis. We examined the levels of the AF-associated miR-328 and the muscle-specific proapoptotic miR-1, and antiapoptotic miR-133A, as well as parameters of apoptosis including the antiapoptotic bcl-2 and the proapoptotic bax mRNAs in 42 patients (31 males and 11 females, mean age 65.0 ± 1.3 years). All patients were in sinus rhythm (SR) prior to CABG. We examined right atrial biopsies taken before aortic cross-clamping and after reperfusion. Atrial miRs, bcl-2 and bax were determined by real-time RT-PCR. After reperfusion following CABG, atrial miR-1, and miR-133A were downregulated by at least 50% (p<0.05) and the bax/bcl-2 ratio was increased approximately 2.5-fold (p<0.05) in all patients. Patients who postoperatively remained in SR (n=28, 24 males and 4 females), showed downregulation of miR-1 by 60% (p<0.05), and a 1.5-fold increase in the bax/bcl-2 ratio (p<0.05). Patients who postoperatively developed AF (n=14, 7 males and 7 females), showed downregulation of miR-133A by 40% (p<0.05), miR-328 by 55% (p<0.05) and a 3.5-fold increase in the bax/bcl-2 (p<0.05). In postoperative AF, differential downregulation of miR-1, miR-133A and miR-328 may contribute to postoperative apoptosis. These results provide new insights into molecular mechanisms of postoperative AF with potential therapeutic implications.