Effects of Remote Ischemic Preconditioning and Myocardial Ischemia on MicroRNA-1 Expression in the Rat Heart In Vivo

Abstract

Remote ischemic preconditioning (RIPC) is an easily applicable method for protecting the heart against a subsequent ischemia and reperfusion (I/R) injury. However, the exact molecular mechanisms underlying RIPC are unknown. We examined the involvement of microRNAs (miRNAs) and in particular the expression of miRNA-1 (miR-1) in RIPC and myocardial ischemia. Remote ischemic preconditioning was conducted by four cycles of 5-min bilateral hind-limb ischemia in male Wistar rats. Cardiac ischemia was induced by ligation of the left anterior descending coronary artery for 35 min followed by 2 or 6 h of reperfusion. MicroRNA expression was analyzed by Taqman miRNA arrays and quantitative polymerase chain reaction assays. Luciferase assays were performed to validate the miR-1 target gene brain-derived neurotrophic factor (BDNF). Brain-derived neurotrophic factor mRNA and protein levels were analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Remote ischemic preconditioning led to a differential expression of miRNAs. The most abundant cardiac miRNA, miR-1, was downregulated by RIPC without following ischemia as well as after I/R and RIPC followed by I/R after 2 h of reperfusion. After 6 h of reperfusion, RIPC led to an upregulation of miR-1, whereas ischemia had no effect on miR-1 expression. Luciferase assays confirmed the interaction of miR-1 with BDNF, a protein that has been shown to exert cardioprotective effects. Brain-derived neurotrophic factor protein levels in rat hearts measured by enzyme-linked immunosorbent assay were not significantly altered after 2 or 6 h of reperfusion in all intervention groups. Remote ischemic preconditioning leads to changes in the expression levels of the most abundant cardiac miRNA, miR-1. MicroRNA 1 levels did not correlate with protein levels of BDNF, a known miR-1 target, in vivo. Further studies are needed to explore the biological significance of changes in miR-1 expression levels and the potential interaction with BDNF in RIPC-induced cardioprotection.

Cardiac over-expression of microRNA-1 induces impairment of cognition in mice

“…Importantly, AMO-1 transfection markedly suppressed the inhibitory effect of miR-1 on p-CREB (P < 0.05). Taken together, these data indicate that BDNF is a potential target of miR-1, which is consistent with the findings of previous studies (Brandenburger et al, 2014;Varendi et al, 2014) .…”

SIRT1 exerts neuroprotective effects by attenuating cerebral ischemia/reperfusion-induced injury via targeting p53/microRNA-22

“…As a complex organ with various cell types, cerebral tissues have different cellular components and synaptic connections at (20). In cerebral tissues, cells of different types have individual expression profiles (44). In the present study, we also demonstrated that SIRT1 exerted neuroprotective effects by increasing microRNA-22 expression in rats with CIRI.…”

MicroRNA-1-associated effects of neuron-specific brain-derived neurotrophic factor gene deletion in dorsal root ganglia

“…Secondly, it has been reported that miR-1 is dysregulated in mouse DRG in different pain states (Kusuda et al, 2011). Thirdly, miR-1 negatively modulates Bdnf gene expression (Brandenburger et al, 2014;Varendi et al, 2014) and inhibits expression of the neuropathic pain-associated proteins Hsp60 and Cx43 (Pan et al, 2012;Shan et al, 2010;Yang et al, 2007). To regulate specific A C C E P T E D M A N U S C R I P T…”

“…The protein is critically involved in pathological nociceptive processes such as neuropathic pain (Coull et al, 2005). It has been demonstrated previously that microRNA-1 (miR-1) negatively regulates BDNF expression by directly targeting the 3` untranslated region (UTR) of Bdnf mRNA (Brandenburger et al, 2014;Varendi et al, 2014).…”