Loss of Snord116 protects cardiomyocyte kinetics during ischemic stress

Abstract

Loss of Snord116, a non-coding RNA, causes Prader Willi Syndrome (PWS), a complex disorder with circadian, metabolic, neurologic, and cardiovascular phenotypes. The Snord116 paternal knockout (Snord116p-) mouse, a model of PWS, demonstrated differential methylation of thousands of genes involved in regulation of metabolism, epigenetics, and ion homeostasis. To determine if Snord116 expression influences the cardiomyocyte response to acute ischemia, we developed a model of ischemia and reperfusion using living myocardial slices and monitored cardiomyocyte function in slices derived from Snord116p- mice and wildtype littermates (WT LM) of both sexes. We found that Snord116 loss reduced ischemia-induced systolic prolongation and delayed diastolic elongation in slices from both males and females. Furthermore, when compared with slices from males, slices from females experienced a greater increase in end-diastolic force after ischemia. We conclude that female myocardium responds more dramatically and quickly to ischemic injury in this model and that loss of Snord116 is cardioprotective; this allows for a more complete myocardial recovery following reperfusion.