Modulation of microRNA 20b with resveratrol and longevinex is linked with their potent anti‐angiogenic action in the ischaemic myocardium and synergestic effects of resveratrol and γ‐tocotrienol

• Published in: Journal of cellular and molecular medicine Vol. 16; no. 10; pp. 2504 - 2517
• Main Authors: Mukhopadhyay, Partha, Das, Somak, Ahsan, Md Kaimul, Otani, Hajime, Das, Dipak K.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-10-2012; John Wiley & Sons, Inc
• Subjects: Aging; Angiogenesis; Angiogenesis Inhibitors - pharmacology; Animals; Apoptosis; Apoptosis - drug effects; Arrays; cardiovascular; Chromans - pharmacology; Diabetes; Down-Regulation; Drug Synergism; Gene expression; Gene Expression Profiling - methods; Heart; Heart - drug effects; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; ischaemia/reperfusion; Ischemia; Laboratory animals; Male; microRNA; MicroRNAs; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; Microscopy; Microscopy, Confocal; miRNA; Multivariate Analysis; Myocardial Ischemia - drug therapy; Myocardial Ischemia - pathology; Myocardium; Myocardium - pathology; Original; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; redox; Reperfusion; Resveratrol; resveratrol/longevinex; Rodents; Signal Transduction; Smad3 protein; Software; Stilbenes - pharmacology; Transcription factors; Transforming growth factor-b1; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vitamin E - analogs & derivatives; Vitamin E - pharmacology; γ‐tocotrienol; Grand Island; United States > US
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/j.1582-4934.2011.01480.x

Resveratrol, a constituent of red wine, and γ‐tocotrienol, a constituent of palm oil are important for cardioprotection. Although microRNAs are known regulators for genes involved in cardiac remodelling, the regulatory pathway involving microRNA has not been studied so far. We explored the cardioprotection by resveratrol, longevinex and γ−tocotrienol in ischaemia/reperfusion(I/R) model of rat and determined miRNA profile from isolated RNA. Systemic analyses of miRNA array and theirs targets were determined using a number of computational approaches. Resveratrol and γ‐tocotrienol, either alone or in combination, modulated the expression pattern of miRNAs close to the control level based on PCA analyses. Differential expression was observed in over 75 miRNAs, some of them, such as miR‐21 and miR‐20b (anti‐angiogenic) were previously implicated in cardiac remodelling. The target genes for the highest differentially expressed miRNA include genes of various molecular functions such as TGFβ1–Smad3 signalling pathway, inflammation and their transcription factors, which may play key role in reducing I/R injury. Administration of antagomiR‐20 attenuated I/R induced vascular endothelial growth factor and HIF1α level. All the interventions treated for 3 weeks lead to significant cardioprotection against ischaemia/reperfusion injury. A unique signature of miRNA profile is observed in control heart pretreated with resveratrol or γ‐tocotrienol. 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 rat. Interestingly, resveratrol and γ‐tocotrienol resulted in synergestic action.