The Mechanisms Of The PI3K-Akt Signaling Pathway And Autophagy In Bone Morphogenetic Protein 4 Induced H9c2 Cardiomyocytes Hypertrophy

BackgroundMyocardial hypertrophy refers to the increase in myocardial volume due to increased load,the expression of intracellular Natriuretic peptide(ANP),B-type natriuretic peptide(BNP),β-myosin heavy chain(β-MHC)Increased cardiac hypertrophy if the compensatory progress for the decompensation,so that the function of the heart can not maintain long-term normal function and lead to heart failure,explore the mechanism of development of cardiac hypertrophy to delay the progress of heart failure has important clinical significance.Bone morphogenetic protein 4(BMP4)is one of the members of the transforming growth factor-beta superfamilies At present,BMP4 has not only induced and promoted bone tissue formation and development,but also can induce pathologic myocardium Hypertrophy,the specific regulatory mechanism is not clear.we investigated the relationship between hypertrophy of H9c2 cardiomyocytes and PI3K-Akt pathway and autophagy in this experiment.ObjectivesTo investigate the mechanism of the PI3K-protein kinase B(PI3K-Akt)signaling pathway and autophagy in BMP4-induced H9c2 rat cardiomyocytes hypertrophy.MethodsCultured rat cardiac cell line H9c2.The H9c2 were randomly divided into four groups(1)normal control(2)BMP4 group(50ng/ml)(3)PI3K inhibitor LY294002 pretreatment120 min,then BMP4(4)3-Methylade-nine(10mmol)pretreatment 120 min,line BMP4 stimulated.The expression change of Akt protein phosphorylation of H9c2 in the four groups were observed at different times(0,1h,4h,8h,12 h,24h)after BMP4(50ng/mL).After 48 hours,Image J measurement of cell surface area,BCA determination of total cell protein content.Western blot determination the expression changes of PI3K、P-PI3K、Akt、P-Akt、α-SMA、BNP.Results: Compared with normal control,cardiac cell area of BMP4(593.73± 53.70);protein content(214.21±19.22);BNP(0.45±0.10).cell area of LY294002+BMP4(256.41±51.31);protein content(134.73±13.83);BNP(0.45±0.10)decrease the area of myocardial cells(P<0.05).BMP4 increases the expression of autophagy associated protein LC3(P<0.01)in hypertrophy.The autophagy inhibitor 3-MA、PI3K/Akt inhibitor LY294002 can reduce the role of BMP4(P<0.05).compared with control,P-Akt induced 1h after BMP4 levels increased(P<0.01).after 3MA、LY294002 treatment,could weaken the BMP4 induced P-PI3 k,P-Akt activation(P<0.05).A significant increase the expression ofα-SMA、BNP after BMP4 stimulated(P<0.01).Conclusion BMP4 may induce hypertrophy of H9c2 cardiomyocytes by activating PI3K-Akt signaling pathway and increase autophagy activity.ConclusionsAfter stimulating of BMP4 in myocardial cells could increase the surface area of myocardial cell and promote the protein content of myocardial cell,and up-regulate the expression of BNP and α-SMA in the myocardium.The autophagy inhibitor 3MA,PI3 K / Akt inhibitor LY294002 Attenuates the treatment of bone morphogenetic protein 4 and may induce hypertrophy of H9c2 cardiomyocytes by activating PI3K-Akt pathway and increasing autophagic activity.