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1559069 
Journal Article 
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 ?-tocotrienol 
Mukhopadhyay, P; Das, S; Ahsan, MdK; Otani, H; Das, DK 
2012 
Yes 
Journal of Cellular and Molecular Medicine
ISSN: 1582-1838
EISSN: 1582-4934 
16 
10 
2504-2517 
22050707 
WOS:000309237500026 
Resveratrol, a constituent of red wine, and ?-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 ?-
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 ?-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 TGF
beta 1Smad3 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 HIF1a 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 ?-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 ?-tocotrienol resulted in synergestic action. 
ischaemia; reperfusion; redox; cardiovascular; microRNA; resveratrol; longevinex; -tocotrienol