Abstract 749: Circulating miRNAs and Apoptosis Genes With Hyperglycemia in Ischemic Stroke Patient

Abstract

Stroke is the third cause of death and the leading cause of adult disability in Taiwan. More than half of acute ischemic stroke patients had hyperglycemia, which is one of the major reason for unfavorable outcomes. However, the physiopathology is remain unclear and better knowledge of underlying genetic mechanisms is needed to improve prognosis. This study aimed to identify possible genes and its regulated miRNA involving in hyperglycemia-induced unfavorable stroke outcomes. This is a two-stage study design. In the first screening stage, 3 hyperglycemia ischemic stroke patients and 3 normal-glycemia cases were recruited. MiRNA sequencing and PCR profile arrays were conducted. Messenger RNA with significant differences and miRNA were analyzed using miRSystem database and Cytoscape. The results showed that apoptosis regulatory pathway genes (FAS and BCL2L1) and its related microRNAs (has-let-7i-5p,has-let-7b-5p,has-let-7a-5p,has-let-7f-5p,has-let-7g-5p,has-let-7e-5p,has-miR-98-5p) were highly associated with acute hyperglycemia ischemic stroke. In the second validation stage, we then verified the above mentioned apoptosis regulatory pathway genes and its related miRNAs using middle cerebral artery occlusion (MCAO) mice model and validate in 143 ischemic stroke patients. From the animal model, the results showed that the FAS gene of hyperglycemic rats exhibited a higher performance than that of normal glycemic rats. The results of miRNAs indicated that the expression of has-let-7a-5p, has-let-7b-5p, has-let-7e-5p, and has-let-7i-5p was lower in hyperglycemia rats than those belonged to normal glycemic rats. For ischemic stroke patients, unfavorable outcome patients had higher FAS expression. Furthermore, there is a significant group-by-time interactions in FAS expression, with unfavorable outcome patients having increasing expression in FAS gene (p=0.0208). A remarkable group-by-time interaction in has-let-7e-5p expression was also observed, with unfavorable outcome patients having decreasing expression in has-let-7e-5p (p=0.0128). Our study uncovers FAS gene play an important role in hyperglycemia resulting in poor outcomes in ischemic stroke patients, and might provide new direction for treatment in the future.