The cardioprotective effect of microRNA-103 inhibitor against isoprenaline-induced myocardial infarction in mice through targeting FADD/RIPK pathway

Abstract

OBJECTIVE: The current study investigates the effect of the innovative phosphorothioate modified backbone locked nucleic acid (LNA) of microRNA-103 (miR-103) specifically designed for systemic delivery in the silencing of miR-103 in experimentally induced myocardial infarction (MI). MicroRNA-103 is a small non-coding RNA which regulates Fas-associated protein with death domain (FADD) gene expression, which is a negative regulator for necroptosis occurs during the progression of MI. MATERIALS AND METHODS: Experimental male mice were allocated into three groups; the first group received normal saline, the second group was injected with isoprenaline and served as the infarcted control, while the third group was treated with LNA miR-103 power inhibitor before isoprenaline injection. Blood and heart samples were used for biochemical analysis of miR-103, FADD, receptor interacting protein kinase (RIPK), nuclear factor-κβ, tumor necrosis factor-α, interleukin-6, troponin-I and creatine kinase-MB (CK-MB) as well as the histological examination of heart tissue. RESULTS: The treated mice showed marked improvement in the troponin-I and CK-MB levels with almost normal histological structure of heart tissue. Significant inhibition of miR-103 accompanied by increased FADD expression and markedly decreased expression of the other biomarkers were observed in the hearts of the treated mice. CONCLUSIONS: LNA miR-103 inhibitor is a potent cardioprotective agent and can be a promising treatment against MI through targeting FADD/RIPK pathway.