LEF1 is a transcriptional repressor which activates HDACs which downregulate expression of many genes important in the pathogenesis of stroke.49 Indeed, HDAC inhibitors in humans can decrease the risk of stroke after a previous stroke or TIA.50 Thus, smoking activation of LEF1 would be expected to activate HDACs which could worsen stroke outcomes. This evidence concerns the gene HDAC9 and Stroke.