Abstract 17186: Genetic Deletion of Circadian Clock Gene Reduces the Extent of Myocardial Ischemia-Reperfusion Injury
Background: The importance of circadian clock is well known in cardiovascular health and disease. Circadian clocks are transcriptionally based molecular mechanisms that regulate cellular function during the course of the day. Previous studies have demonstrated that circadian clock genes contribute to daily changes in heart rate and blood pressure. In the present study we investigated the effects of genetic deficiency of the Clock gene on the severity of myocardial ischemia-reperfuson (MI-R) injury.
Methods: Wild-type (WT) and Clock knockout (KO) mice (24-27 weeks) were utilized for the study. 2-D echocardiography was performed at baseline to assess heart rate (HR) and left ventricular (LV) function for both Clock KO and WT mice. Mice (n=9-13) were subjected to 45 min of myocardial ischemia (MI) induced by left coronary artery occlusion and 24 hrs of R in vivo. LV area-at-risk (AAR) and infarct (INF) size were determined with Evan's blue dye and 2,3,5-triphenyl tetrazolium chloride (TTC) staining.
Results: We failed to observe any differences in HR between the WT (491±18 BPM) and Clock KO (471±15 BPM) mice (p=NS). In addition, LV ejection fraction was similar in WT (63 ± 2%) and Clock KO (63 ± 2%) mice (p=NS). However, we did observe a significant reduction in myocardial infarct size with respect to area-at-risk of Clock KO mice compared to (WT) mice (25.5 ± 3% vs. 41.8± 6%, respectively, p < 0.01).
Conclusions: While additional studies are required to define the precise cellular and molecular signals that are influenced by the circadian clock at the time of MI-R injury, these studies suggest that Clock does exert a significant influence in the onset of pathology during myocardial infarction.
- © 2011 by American Heart Association, Inc.