Restoration of Altered MicroRNA Expression in the Ischemic Heart with Resveratrol

Abstract

BackgroundResveratrol, a constituent of red wine, is important for cardioprotection. MicroRNAs are known regulators for genes involved in resveratrol-mediated cardiac remodeling and the regulatory pathway involving microRNA has not been studied so far.MethodsWe explored the cardioprotection by resveratrol in ischemia/reperfusion model of rat and determined cardiac functions. miRNA profile was determined from isolated RNA using quantitative Real-time PCR based array. Systemic analyses of miRNA array and theirs targets were determined using a number of computational approaches.ResultsCardioprotection by resveratrol and its derivative in ischemia/reperfusion [I/R] rat model was examined with miRNA expression profile. Unique expression pattern were found for each sample, particularly with resveratrol [pure compound] and longevinex [commercial resveratrol formulation] pretreated hearts. Longevinex and resveratrol pretreatment modulates the expression pattern of miRNAs close to the control level based on PCA analyses. Differential expression was observed in over 25 miRNAs, some of them, such as miR-21 were previously implicated in cardiac remodeling. The target genes for the differentially expressed miRNA include genes of various molecular function such as metal ion binding, sodium-potassium ion, transcription factors, which may play key role in reducing I/R injury.ConclusionRats pretreated with resveratrol for 3 weeks leads to significant cardioprotection against ischemia/reperfusion injury. A unique signature of miRNA profile is observed in control heart pretreated with resveratrol or longevinex. We have determined specific group of miRNA in heart that have altered during IR injuries. Most of those altered microRNA expressions modulated close to their basal level in resveratrol or longevinex treated I/R mice.

Pro-apoptotic versus anti-apoptotic properties of dietary resveratrol on tumoral and normal cardiac cells

“…The determination of the part taken by miRNAs in Rsv sensitivity can have some pharmacological interests to improve Rsv efficiency in various major diseases such as cardiovascular diseases and cancers. Indeed, very recently, it has been reported that resveratrol restores the expression of some altered micro-RNA in the ischemic rat heart (Mukhopadhyay et al 2010). Moreover, the present data also support our objectives to develop nutraceutical and functional foods based on dietary Rsv with the aim to prevent or reverse cardiac dysfunctions and diseases.…”

Ischemic postconditioning improves the expression of cellular membrane connexin 43 and attenuates the reperfusion injury in rat acute myocardial infarction

“…The IR model was prepared with 8-week-old male Sprague-Dawley rats weighing 260-310 g (Laboratory Animal Division, Medicine Department, Beijing University, Beijing, China), as described previously (11). The sternum was incised and the heart was exposed subsequent to anesthetizing with 1% pentobarbital (40 mg/kg body weight) through peritoneal injection and support from a breathing machine.…”

MicroRNAs as targets for dietary and pharmacological inhibitors of mutagenesis and carcinogenesis

“…The upregulated miRNAs included miR-20b and miR-21 (antiangiogenic), which are implicated in cardiac remodeling. These data suggest that resveratrol exerts a significant cardioprotection through miRNA modulation [69,70]. …”