MiR-21/PTEN/AKT Signal Pathway Contributes To Mice Cardiac Aging

BackgroundAging is among predominant risk factors for cardiovascular diseases.MicroRNAs(miRNAs)participate in many physiological and pathological processes in the cardiovascular system.However,the role of miRNAs in cardiac aging has not been completely understood.Our preliminary data showed that miR-21 was upregulated in the heart tissue of two types of aging mice models.In this project,we tried to clarify the relationship between miR-21 and cardiac aging and to expound the molecular mechanism of miR-21 in heart aging.Methods1)MiRNA global screening was performed on adult mice and natural aging mice heart tissue to select the high expression of miRNAs in aging heart tissue specimens.We validated the result of the microarray chip by the qRT-PCR as well in aging neonatal rat left ventricle myocyte(NRVMs)and senescence mice induced respectively by Doxorubicin(DOX)and D-Galactose(D-Gal).2)Based on the aging cell induced by DOX,we transfected miR-21 mimics and miR-21 inhibitor in NRVMs to verify the function of miR-21 in senescence.3)By the methods of PCR and Western blot,we preliminary screened the target genes of miR-21 in cardiac aging.4)To clarify the molecular mechanism of miR-21 in cardiac aging in vitro.Results1)The expressions of miR-21 were significantly increased in the cardiac tissues of two types aging mice models and senescence cell model induced by DOX.2)Up-regulated the expression of miR-21 was able to cause the newborn rat myocardiocytes aging which was necessary with the myocytes aging induced by DOX.3)PTEN(Phosphatase and Tensin homolog deleted on chromosome Ten)is the direct target of miR-21.miR-21 inhibitor can reverse the newborn rat myocardiocytes aging induced by PTEN small interfering RNA(siPTEN).Conclusion These findings reveal miR-21/PTEN/AKT signaling pathway plays an important role in the development of cardiac aging,which may be new targets to intervent cardiac aging.