Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p

Abstract

BackgroundLuteolin (LUT), a kind of flavonoid which is extracted from a variety of diets, has been reported to convey protective effects of various diseases. Recent researches have suggested that LUT can carry out cardioprotective effects during ischemia/reperfusion (I/R). However, there have no reports on whether LUT can exert protective effects against myocardial I/R injury through the actions of specific microRNAs (miRs). The purpose of this study was to determine which miRs and target genes LUT exerted such function through.MethodsExpression of various miRs in perfused rat hearts was detected using a gene chip. Target genes were predicted with TargetScan, MiRDB and MiRanda. Anoxia/reoxygenation was used to simulate I/R. Cells were transfected by miR-208b-3p mimic, inhibitor and small interfering RNA of Ets1 (avian erythroblastosis virus E26 (v ets) oncogene homolog 1). MiR-208b-3p and Ets1 mRNA were quantified by real-time quantitative polymerase chain reaction. The percentage of apoptotic cells was detected by annexin V-fluorescein isothiocyanate/propidium iodide dyeing and flow cytometry. The protein expression levels of cleaved caspase-3, Bcl-2, Bax, and Ets1 were examined by western blot analysis. A luciferase reporter assay was used to verify the combination between miR-208b-3p and the 3’-untranslated region of Ets1.ResultsLUT pretreatment reduced miR-208b-3p expression in myocardial tissue, as compared to the I/R group. And LUT decreased miR-208b-3p expression and apoptosis caused by I/R. However, overexpression of miR-208b-3p further aggravated the changes caused by I/R and blocked all the effects of LUT. Knockdown of miR-208b-3p expression also attenuated apoptosis, while knockdown of Ets1 promoted apoptosis. Further, the luciferase reporter assay showed that miR-208b-3p could inhibit Ets1 expression.ConclusionLUT pretreatment conveys anti-apoptotic effects after myocardial I/R injury by decreasing miR-208b-3p and increasing Ets1 expression levels.

Luteolin Modulates SERCA2a Leading to Attenuation of Myocardial Ischemia/ Reperfusion Injury via Sumoylation at Lysine 585 in Mice

“…Luteolin (Lut) is a natural soluble flavone present in many plants. Our previous studies have demonstrated that Lut can protect the myocardium from I/R injury by down-regulating microRNA-208b-3p [17] and the PI3K/Akt pathway [18]. Moreover, decreased expression and activity of SERCA2a can be partly reversed by Lut [19, 20].…”

At the crossroads from bench to bedside: luteolin is a promising pharmacological agent against myocardial ischemia reperfusion injury

“…In this regard, cardioprotection is not lost in translation. Then, we reviewed again our previous study which verified the positive cardioprotective effects of Lut against IRI both in Langendorff perfused rat hearts and the H9c2 cells (1). According to the literature (14), the results would be more convincing if the animal model is similar to the clinical setting.…”

“…The study by Bian et al (1) found that luteolin (Lut) inhibited myocardial ischemia/reperfusion injury (IRI) by decreasing miR-208b-3p and increasing Ets1 expression levels in rats. Cokkinos (2) has written an editorial commentary for this study and considered it to be elegant.…”

“…MicroRNAs (miRNAs) are noncoding RNA involved in the post-transcriptional regulation of protein expression, it has been demonstrated that miRNAs may contribute to classical IPC cardioprotection (40). According to the results of recent studies (1,(41)(42)(43), Lut is an interesting agent, it not only can play a role in multi-signalling pathway, but also can modulate miRNAs in the cardioprotection. The role of Lut in modulating miR-146b-5p and SECA2a/BAG1 against myocardial IRI is processing in our study.…”

“…T h e m i R -2 0 8 b -3 p p l a y a s i g n i f i c a n t r o l e b y reduce apoptosis against IRI, it has important clinical consequences (1). Moreover, miR-208b-3p has been associated with post infarct myocardial remodeling (44).…”