141-OR: Cardioprotective Effect of Empagliflozin and Modification of Sirtuins and Their Noncoding RNAs Regulators in Patients with Myocardial Infarction
Abstract
Introduction: Studies have demonstrated direct cardio-protective effect of SGLT2 inhibitors, but the mechanism of action is unclear. We hypothesize that cardioprotective effects of SGLT2 inhibitors are due to increased expressions of Sirtuins and their regulator-miRNAs.
Method: We conducted in silico prediction analysis using a computational approach. We identified/ranked the most promising ncRNAs associated with sirtuin pathways and SGLT2. We identified top miRNAs by preparing a gene list of all SIRT genes, 1st and 2nd level SGLT2 interactors, and genes involved in inflammation, fibrosis, oxidative stress, hypoxia-ischemia, MI and HF based on DisGeNet database. We validated our findings through qRT-PCR using selected plasma samples (empagliflozin/placebo=24/24; baseline, 26-weeks after treatment) collected from the double-blinded EMMY clinical trial (NCT03087773).
Results: Our in silico analysis identified six miRNAs; miR-34a-5p, miR-27a-3p, miR-302a-3p, miR-146a-5p, miR-182-5p and miR-124-3p, which target the highest number of SIRT1-7 genes, SGLT2 and first-level SGLT2 interactors. qRT-PCR analysis showed that after 26 weeks of treatment, patients taking empagliflozin had significantly higher expression of miR-214 (p=0,015), miR-34a (p<0,001), miR-146a (p<0,001), miR-182-5p (p<0,001) and SIRT2 (p=0,005) compared to baseline. We also found that patients taking empagliflozin had significantly higher expression of SIRT6 (p=0,036), and significantly lower expression of miR-214…
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