| Background and Aim:Cardiac hypertrophy is a hypertrophic pathology change caused by multiple factors,which can gradually lead to a decline in cardiac function.Cardiomyocyte hypertrophy and interstitial hyperplasia are the most basic characteristics.The mechanism has not been fully elucidated.Recently,microRNA has been found to play a wide regulatory role in organisms.The purpose of this study was to observe the role of miR-214 in the pathogenesis of cardiac hypertrophy and to explore the mechanism of its action.Methods:1.150 wild type(WT)mice were divided into 3 groups(n=50)according to body weight,and each body-weight group was divided into 5 operation groups(n = 10).They were used in 4 abdominal aorta constriction group(AAC group)and a sham group(sham group).To observe the survival rate after modeling,and to calculate the cardiac hypertrophy related index.To find the most suitable modeling manner..2.Neonatal rat cardiac myocytes(NRCM)were cultured and hypertrophic change was induced by phenylephrine(PE).Bioinformatics was used to identify the functional target gene of miR-214.Verify the regulatory relationship between mir-214 and predictive target genes through detection of target gene protein expression and double luciferase report experiment.Verify the effect of miR-214 and its target gene on the regulation of myocardial hypertrophy related protein and downstream signal pathway in vitro.3.Myocardial miR-214 conditioned knockout(KO)mice were obtained and identified.The function of miR-214 on cardiac hypertrophy was assessed by researching the difference of hypertrophic changes between WT and KO mice after AAC,in order to elucidate the effect of miR-214 on cardiac hypertrophy by differentiating the expression of target proteins in vivo.Results:1.Excessive constriction of AAC could lead to death in mice,and the mortality was positively related to body weight under the same ligation intensity.Cardiac hypertrophy model could be established by using needles with outer diameter of 0.45 mm and 0.50 mm,which resulted in the increase of myocytes hypertrophy and interstitial hyperplasia in mice.Reduced cardiac function and limited physical development were also observed.2.Bioinformatics predicted that pim-1 might be the target gene of mir-214.Double luciferase report suggested that mir-214 binded to the 3’UTR of pim-1 and reduced the transcriptional activity of pim-1.Antagonistic miR-214 could increase the expression of pim-1,and overexpression of miR-214 inhibited the expression of pim-1.It was further confirmed that there was a direct regulatory relationship between miR-214 and pim-1.3.In vitro,the expression of cardiac hypertrophy related proteins(ANP,BNP,and Myh7)were significantly decreased under overexpression of miR-214.After inhibiting the expression of mir-214,myocardial hypertrophy related protein increased significantly.Further studies had shown that miR-214 could inhibit the expression of pim-1 and the activation of JAK/STAT signaling pathway,thereby affecting the expression of hypertrophy related proteins in myocardium.4.The expression of miR-214 decreased and the expression of pim-1,ANP,BNP,and Myh7 increased in cardiac hypertrophy model of WT mice with AAC,the expression of these proteins were higher In KO mice exposed to AAC.Conclusion:Our team successfully established the model of cardiac hypertrophy,and found that miR-214 played an important role in cardiomyocytes.miR-214 could reduce the expression of pim-1,then inhibited the activation of JAK/STAT signaling pathway and reduced the degree of myocardial hypertrophy.And cardiac hypertrophy was aggravated in deficiency of miR-214 in vivo.Therefore,miR-214 may be a new target for the prevention and treatment of cardiac hypertrophy and related diseases. |
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