Abstract 15934: Microrna-27a Regulates Cardiomyocytic Apoptosis During Cardioplegia-Induced Cardiac Arrest Under Cardiopulmonary Bypass by Targeting Interleukin-10-Related Pathway
Background: MicroRNAs (miRs) had powerful and unexpected roles in numerous cardiovascular diseases. miR-based therapeutic may provide a unique opportunity to translate this knowledge into the clinical setting. Whether miRs had a role in the regulation or modulation of cardiomyocytic reactions under cardioplegia-induced cardiac arrest during cardiopulmonary bypass had not been studied.
Methods and Results: Mice (10 in each group) were randomly divided into three groups: control (sham operation), perfusion, and arrest groups. In the perfusion group, isolated hearts were perfused with oxygenated PBS solution for 3 hours using Langendorff apparatus. In the arrest group, cold (4 °C) crystalloid cardioplegia was used to induce and maintain (every 20 minutes) cardiac arrest for one hour and reperfused for 2 hours with warm oxygenated PBS solution. The cardiac miRs and proteins expression pattern among three groups were detected using miRNA array and 2-D fluorescence difference gel electrophoresis followed with MALDI-TOF MS, respectively. Of 103 different miRs and 222 different proteins expression patterns among three groups, miR-27a was considered to be related in regulating the cardiomyocytic apoptosis by targeting interleukin-10 pathway. Transfection of H9c2 cardiomyocytes with pre-miR-27a vector could significantly decrease the mRNA and protein levels of interleukin-10 during hypoxia/reperfusion injury, which resulted in increasing expression of NFkB and its' downstream cytokines, activation of caspases-3, and occurrence of apoptosis.
Conclusions: Our study showed the regulation of miRNAs in cardiomyocytes under cardioplegia-induced cardiac arrest under cardiopulmonary bypass. The effect on microRNA involved in cardiomyocytic apoptosis adds another level of complexity to gene regulation, which could open up novel avenues in cardiac protection strategies during cardiac surgery.
- © 2011 by American Heart Association, Inc.