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We have previously identified cardiac microRNA\u2010125b* (microRNA\u2010125b\u20102\u20103p; miR\u2010125b*) as a potential cardioprotective miRNA, termed ProtectomiR. We aimed to characterize the pharmacokinetics and pharmacodynamics, and the effect of miR\u2010125b* mimic on infarct size using an in vivo mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach<\/jats:title><jats:p>To characterize the pharmacokinetics properties of miR\u2010125b* mimic, a single injection of 10\u2010\u03bcg miR\u2010125b* mimic or its scramble miRNA control, or vehicle i.v. was given to C57BL\/6 mice. MiR\u2010125b* expression was measured from plasma, heart, kidney and liver samples. Effect of miR\u2010125b* on area at risk and infarct size was assessed after 45\u2010min coronary occlusion, followed by 24\u2010h reperfusion; 10\u2010\u03bcg miR\u2010125b* mimic or 10\u2010\u03bcg non\u2010targeting miRNA mimic control or vehicle were administered via the right jugular vein at 10th mins of coronary occlusion. To assess molecular mechanism involved in cardioprotection, expression of mRNA targets of miR\u2010125b* were measured from ventricular myocardium at 1, 2, 4, 8 or 24\u2009h\u00a0post\u2010treatment using quantitative real time polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results<\/jats:title><jats:p>MiR\u2010125b* expression was markedly increased in plasma and myocardium 1\u00a0h, and in the liver 2h after treatment. Infarct size was significantly reduced after miR\u2010125b* mimic treatment when compared to the vehicle. The expression of <jats:italic>Ccna2<\/jats:italic>, <jats:italic>Eef2k<\/jats:italic> and <jats:italic>Ca<\/jats:italic><jats:italic>c<\/jats:italic><jats:italic>nb2<\/jats:italic> target mRNAs was significantly reduced 8\u00a0h after injection of miR\u2010125b* mimic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and implications<\/jats:title><jats:p>This is the first demonstration of pharmacokinetic and molecular pharmacodynamic properties as well as the cardioprotective effect of miR\u2010125b* mimic <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>LINKED ARTICLES<\/jats:title><jats:p>This article is part of a themed issue Non\u2010coding RNA Therapeutics. 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